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Clinical Trial Results:
Personalised Electronic Record Supported OptimisatioN when ALone for Patients with Hypertension- Pilot Study for Remote Medical Management of Hypertension During the COVID-19 Pandemic

Summary
EudraCT number	2020-002494-10
Trial protocol	GB
Global end of trial date	19 Nov 2021

Results information
Results version number	v1(current)
This version publication date	08 Oct 2023
First version publication date	08 Oct 2023
Other versions
Summary report(s)	Whose Dose is it Anyway ACC Abstract PERSONAL-COVIDBP Personalized electronic record supported optimisation when alone for patients with hypertension- pilot study for remote medical management of hypertension during the Covid-19 pandemic (personal covidB

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

012665

ISRCTN number

ISRCTN16393332

US NCT number

NCT04559074

WHO universal trial number (UTN)

Other trial identifiers

IRAS number: 283209, REC number: 20/HRA/2988

Sponsor organisation name

Queen Mary University of London

Sponsor organisation address

Mile End Road, London, United Kingdom, E1 4NS

Public contact

Dr David Collier, Queen Mary University of London, +44 07961 383925, d.j.collier@qmul.ac.uk

Scientific contact

Dr David Collier, Queen Mary University of London, +44 07961 383925, d.j.collier@qmul.ac.uk

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

07 Mar 2022

Is this the analysis of the primary completion data?

Yes

Primary completion date

10 Nov 2021

Global end of trial reached?

Yes

Global end of trial date

19 Nov 2021

Was the trial ended prematurely?

Main objective of the trial

The primary research objective is to assess how effective precision dosing of amlodipine is in managing blood pressure in participants with primary hypertension and inadequate blood pressure control. Amlodipine will be up-titrated in 1-2mg increments, under a remote medical management protocol during the COVID-19 pandemic. This study will involve the use of a digital diary on which home blood pressure recording will be entered by the participant. During the early part of the study blood pressure recordings will be assessed by the study team to see if the participant should stay on their existing medication regime- if blood pressure is okay- or if blood pressure is raised, participants will be sent liquid amlodipine in the post and the dose of this will be adjusted with the aim of better blood pressure control. The study aims to test the effect of this extra medication regime- both before and after.

Protection of trial subjects

Subjects were remotely assessed for blood pressure control using home monitoring with a machine being supplied by the study team if required. If readings between screening and baseline were elevated, subjects were allocated to intervention and sent liquid amlodipine bulk supply. For intervention subjects regular 1-2 weekly reviews on BP with study team allowed titration of the dose of amlodipine from 1mg daily to 10mg daily, in 1-2mg steps. For those subjects at baseline having adequate BP control, allocated to observation, they continued to measure BP each morning and evening for the three months of the trial. These subjects had remote visits every month or so with the study team to assess BP control on existing medication. For safety of the subjects, those in observation could qualify for the intervention part of the study if their 7-day average BP was above the entry level for the intervention group. 24 trial subjects from the observation group progressed to join the start of the intervention during the study period (for some this meant contributing data for the full 3 months of the intervention group and then another 14 weeks of intervention.) In this way even subjects assessed at baseline to have adequate BP control still got regular remote BP checks and remote consultations. Subjects contributed BP data each morning and evening for the duration of the trial, completed medication dosing information and any covid-19 symptoms and likely amlodipine unwanted effects in the electronic dairy.

Background therapy

Subjects had all had a diagnosis of hypertension and most were treated with medication at the time of screening. Background BP lowering therapy was allowed with the exception of amlodipine 10mg, as this is the maximum licensed dose of amlodipine and could not be increased under the protocol, so such subjects were excluded from the trial. Otherwise, subjects were taking CCB's (mostly amlodipine at doses <10mg daily), ACE inhibitors, ARB's, diuretics, alpha blockers, beta blockers, few on mineralocorticoid receptor antagonists. Background BP therapy remained constant throughout the trial.

Evidence for comparator

As the gradual titration of amlodipine liquid supplied to the intervention arm subjects, usually 1-2mg at a time, was going to take up to 12 weeks, then it was not possible to use a placebo for the comparison arm of the study (evidence of safety on placebo in BP trials is extensive but limited to 8 weeks). The placebo liquid was not available either. Therefore, there was no placebo comparison group in the study.

Actual start date of recruitment

23 Oct 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 343

Worldwide total number of subjects

343

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

208

From 65 to 84 years

134

85 years and over

Subject disposition

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Recruitment details

UK only recruitment began screening on 23 Oct 2020 using clinic, GP, commercial radio advert and direct text from GP's (UMed Ltd). Recruitment closed 28 July 2021 having completed recruitment into the intervention arm, on which the designed power was based (planned for 200 in intervention, actual 205 subjects).

Screening details

Consenting adult subjects with a diagnosis of hypertension were screened on their existing background BP medications, excluded if they were already on maximal amlodipine (10mg daily), did not have a suitable working smartphone, serious reactions to amlodipine, history suggestive of heart failure or aortic stenosis or inadequate contraception.

Period 1 title

Intervention Trial

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Blinding implementation details

Open label study

Intervention

Arm description

Eligible study participants with primary hypertension and inadequate BP control were invited to enrol into the intervention arm of the study, and receive an antihypertensive treatment regimen of precision dosing of liquid amlodipine by up-titration in daily dose in small increments of 1-2mg, under a remote medical management and smartphone app-enabled protocol during the COVID-19 pandemic.

Arm type

Experimental

Investigational medicinal product name

Amlodipine (type of calcium channel blocker)

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

Drug in liquid form to be taken orally once daily (AM) and not to exceed 10mg daily dose.

Number of subjects in period 1 ^[1]	Intervention
Started	205
Baseline	205
Week 1	203
Week 2	203
Week 4	203
Week 6	200
Week 8	199
Week 10	198
Week 12	196
Week 14 (end of trial visit)	196
Completed	196
Not completed	9
Adverse event, non-fatal	1
Lost to follow-up	8

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: 205 subjects were enrolled into the Intervention arm, but the total number of patients enrolled into study (both Intervention arm and Observation arm) was 343. Note that 24 subjects who were originally enrolled into the Observation arm, were subsequently enrolled into the Intervention arm.

Period 2 title

Observation study

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Observation

Arm description

Consenting participants with controlled blood pressure at baseline were invited to enrol into an observation arm. Participants in the observation arm did not receive study medication, but were medically managed and observed with a smartphone app-enabled protocol. If participants in the observation arm presented with uncontrolled blood pressure when reviewed at a study visit, they were invited to enrol into the intervention arm of the study.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 2 ^[2] ^[3]	Observation
Started	162
Baseline	162
1 Month	157
2 Months	142
3 Months (end of study)	133
Completed	133
Not completed	29
Transferred to other arm/group	17
Lost to follow-up	12

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: 162 subjects were enrolled into the Observation arm, but the total number of patients enrolled into study (both Intervention arm and Observation arm) was 343. Note that 24 subjects who were originally enrolled into the Observation arm, were subsequently enrolled into the Intervention arm.
[3] - The number of subjects transferring in and out of the arms in the period are not the same. It is expected the net number of transfers in and out of the arms in a period, will be zero.
Justification: Subjects in the Observation arm were only able to transfer out and into the Intervention arm. No subjects who initially were enrolled into the Intervention cohort were subsequently enrolled into the Observation arm.

Baseline characteristics

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Reporting group title

Intervention

Reporting group description

Reporting group values	Intervention	Total
Number of subjects	205	205
Age categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	0	0
Adolescents (12-17 years)	0	0
Adults (18-64 years)	129	129
From 65-84 years	75	75
85 years and over	1	1
Age continuous
Units: years
arithmetic mean (standard deviation)	60.05 ± 10.97	-
Gender categorical
Units: Subjects
Female	68	68
Male	137	137
Ethnicity
Units: Subjects
Asian	25	25
Black	20	20
Mixed	1	1
White	149	149
Unknown/not reported	2	2
Other	8	8
Smoking status
Units: Subjects
Non-smoker	124	124
Previous smoker	59	59
Current smoker	21	21
Unknown/not reported	1	1
Diabetes
Units: Subjects
Yes	19	19
No	186	186
Kidney dysfunction
Units: Subjects
Yes	1	1
No	204	204
Peripheral arterial/vascular dysfunction
Units: Subjects
Yes	3	3
No	202	202
Hypercholesterolaemia
Units: Subjects
Yes	42	42
No	163	163
Previous stroke
Units: Subjects
Yes	0	0
No	205	205
Previous MI
Units: Subjects
Yes	3	3
No	202	202
Previous PCI
Units: Subjects
Yes	0	0
No	205	205
Number of antihypertensive medications on at baseline
Units: Subjects
None	49	49
One	86	86
Two or more	70	70
Body Mass Index
Units: kg/m2)
arithmetic mean (standard deviation)	28.85 ± 5.27	-
Systolic blood pressure (home 7-day mean)
Units: mmHg
arithmetic mean (standard deviation)	141.95 ± 9.75	-
Diastolic blood pressure (home 7-day mean)
Units: mmHg
arithmetic mean (standard deviation)	86.97 ± 8.09	-
Heart rate (home 7-day mean)
Units: beats per minute
arithmetic mean (standard deviation)	71.46 ± 10.88	-

End points

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Reporting group title

Intervention

Reporting group description

Reporting group title

Observation

Reporting group description

Primary: Change in systolic blood pressure from baseline to the end of the trial (Week 14)

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End point title

Change in systolic blood pressure from baseline to the end of the trial (Week 14) ^[1]

End point description

The timing of the final visit is approximately 14 weeks after their baseline visit in the intervention arm, but exact time-span varies slightly between subjects. Mean systolic blood pressure was calculated using all available home blood pressure measurements within the 7-day lead-up to baseline and the end of trial visit (Week 14) to represent baseline and end of trial mean systolic blood pressure for each study participant. Mean systolic blood pressure was also calculated in this way at each of the scheduled visits. The difference in mean systolic blood pressure between baseline and the end of trial visit (Week 14) was estimated from a linear mixed effects model, with each visit in the model as indicator variables for the fixed effects, with a random component for study participant.

End point type

Primary

End point timeframe

From baseline (Day 0) to the end of trial visit (at Week 14).

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The primary endpoint if the change in systolic blood pressure between baseline and the end of the trial, in the Intervention arm only. There is no comparator group. In order to enter statistical analysis into EudraCT, at least 1 comparator group needs to be specified, which is not relevant in this study.

End point values	Intervention
Number of subjects analysed	205
Units: mmHg
least squares mean (confidence interval 95%)	-11.02 (-11.99 to -10.06)

No statistical analyses for this end point

Secondary: Change in diastolic blood pressure from baseline to the end of the trial (Week 14)

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End point title

Change in diastolic blood pressure from baseline to the end of the trial (Week 14)

End point description

The timing of the final visit is approximately 14 weeks after their baseline visit in the intervention arm, but exact time-span varies slightly between subjects. Mean diastolic blood pressure was calculated using all available home blood pressure measurements within the 7-day lead-up to baseline and the end of trial visit (Week 14) to represent baseline and end of trial mean diastolic blood pressure for each study participant. Mean diastolic blood pressure was also calculated in this way at each of the scheduled visits. The difference in mean diastolic blood pressure between baseline and the end of trial visit (Week 14) was estimated from a linear mixed effects model, with each visit in the model as indicator variables for the fixed effects, with a random component for study participant.

End point type

Secondary

End point timeframe

From baseline (Day 0) to the end of trial visit (at Week 14).

End point values	Intervention
Number of subjects analysed	205
Units: mmHg
least squares mean (confidence interval 95%)	-6.50 (-7.10 to -5.91)

No statistical analyses for this end point

Secondary: Achieving blood pressure target less than 135 mmHg systolic and less than 85 mmHg diastolic blood pressure at the end of the trial (Week 14)

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End point title

Achieving blood pressure target less than 135 mmHg systolic and less than 85 mmHg diastolic blood pressure at the end of the trial (Week 14)

End point description

SBP<135 and DBP<85 mmHg at the end of the trial (Week 14)

End point type

Secondary

End point timeframe

At the end of the trial (Week 14)

End point values	Intervention
Number of subjects analysed	189 ^[2]
Units: Positive integers	102

Notes
[2] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Achieving reduction of 5 or more mmHg systolic blood pressure by the end of the trial (Week 14)

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End point title

Achieving reduction of 5 or more mmHg systolic blood pressure by the end of the trial (Week 14)

End point description

Reduction in SBP ≥5 mmHg at the end of treatment (Week 14) as compared to baseline.

End point type

Secondary

End point timeframe

Change in SBP at the end of treatment (Week 14) as compared to baseline.

End point values	Intervention
Number of subjects analysed	189 ^[3]
Units: Positive integer	136

Notes
[3] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Achieving reduction of 10 or more mmHg systolic blood pressure by the end of the trial (Week 14)

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End point title

Achieving reduction of 10 or more mmHg systolic blood pressure by the end of the trial (Week 14)

End point description

End point type

Secondary

End point timeframe

Change in SBP at the end of treatment (Week 14) as compared to baseline.

End point values	Intervention
Number of subjects analysed	189 ^[4]
Units: Positive integer	98

Notes
[4] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Achieving reduction of 5 or more mmHg diastolic blood pressure by the end of the trial (Week 14)

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End point title

Achieving reduction of 5 or more mmHg diastolic blood pressure by the end of the trial (Week 14)

End point description

Reduction in DBP ≥5 mmHg at the end of treatment (Week 14) as compared to baseline.

End point type

Secondary

End point timeframe

Change in DBP at the end of treatment (Week 14) as compared to baseline.

End point values	Intervention
Number of subjects analysed	189 ^[5]
Units: Positive integer	122

Notes
[5] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Achieving combination of target blood pressure & specified reductions in blood pressure by the end of the trial (Week 14)

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End point title

Achieving combination of target blood pressure & specified reductions in blood pressure by the end of the trial (Week 14)

End point description

A combination of SBP<135 and DBP<85 mmHg at the end of the trial (Week 14), a reduction in SBP ≥10mmHg and a reduction in DBP ≥5mmHg from baseline to the end of the trial (Week 14).

End point type

Secondary

End point timeframe

At the end of treatment (Week 14) as compared to baseline.

End point values	Intervention
Number of subjects analysed	189 ^[6]
Units: Positive integer	53

Notes
[6] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Median time to achieving blood pressure control

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End point title

Median time to achieving blood pressure control

End point description

Using a Kaplan-Meier survival estimates approach, the median time to achieving blood pressure control, defined as an ABP <135 mmHg and a DBP <85 mmHg, was calculated.

End point type

Secondary

End point timeframe

From baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	205
Units: Weeks
median (confidence interval 95%)	5.29 (3.86 to 6.57)

No statistical analyses for this end point

Secondary: Self-reported side effects (Any of the main 6)

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End point title

Self-reported side effects (Any of the main 6)

End point description

Self-reporting of side effects was done via the digital diary, with each type of side effect scored on a visual analogue scale (VAS) from 0-100 (positive integers). The main 6 side effects were: headache, swelling, skin reaction, abdominal pain, fatigue or drowsiness, nausea or vomiting. This endpoint categorises any of these 6 reported side effects ever reported as mild or worse (over 0 on the VAS), moderate or worse (over 25 on the VAS), severe or worse (over 75 on the VAS), or very severe (over 75 on the VAS).

End point type

Secondary

End point timeframe

From baseline to the end of the trial (Week 14)

End point values	Intervention
Number of subjects analysed	196 ^[7]
Units: Positive integers
Mild or worse	161
Moderate or worse	116
Severe or worse	67
Very severe	20

Notes
[7] - Subjects who completed the trial. Note, subjects can appear in more than one category.

No statistical analyses for this end point

Secondary: Self-reported side effects (headache)

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End point title

Self-reported side effects (headache)

End point description

Self-reporting of side effects was done via the digital diary, with each type of side effect scored on a visual analogue scale (VAS) from 0-100 (positive integers). This endpoint categorises self-reported headache side effects ever reported as mild or worse (over 0 on the VAS), moderate or worse (over 25 on the VAS), severe or worse (over 75 on the VAS), or very severe (over 75 on the VAS).

End point type

Secondary

End point timeframe

From baseline to the end of the trial (Week 14)

End point values	Intervention
Number of subjects analysed	196 ^[8]
Units: Positive integer
Mild or worse	112
Moderate or worse	62
Severe or worse	21
Very severe	4

Notes
[8] - Subjects who completed the trial. Note, subjects can appear in more than one category.

No statistical analyses for this end point

Secondary: Self-reported side effects (swelling)

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End point title

Self-reported side effects (swelling)

End point description

Self-reporting of side effects was done via the digital diary, with each type of side effect scored on a visual analogue scale (VAS) from 0-100 (positive integers). This endpoint categorises self-reported swelling side effects ever reported as mild or worse (over 0 on the VAS), moderate or worse (over 25 on the VAS), severe or worse (over 75 on the VAS), or very severe (over 75 on the VAS).

End point type

Secondary

End point timeframe

From baseline to the end of the trial (Week 14)

End point values	Intervention
Number of subjects analysed	196 ^[9]
Units: Positive integer
Mild or worse	74
Moderate or worse	41
Severe or worse	19
Very severe	6

Notes
[9] - Subjects who completed the trial. Note, subjects can appear in more than one category.

No statistical analyses for this end point

Secondary: Self-reported side effects (skin reaction)

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End point title

Self-reported side effects (skin reaction)

End point description

Self-reporting of side effects was done via the digital diary, with each type of side effect scored on a visual analogue scale (VAS) from 0-100 (positive integers). This endpoint categorises self-reported skin reaction side effects ever reported as mild or worse (over 0 on the VAS), moderate or worse (over 25 on the VAS), severe or worse (over 75 on the VAS), or very severe (over 75 on the VAS).

End point type

Secondary

End point timeframe

From baseline to the end of the trial (Week 14)

End point values	Intervention
Number of subjects analysed	196 ^[10]
Units: Positive integer
Mild or worse	51
Moderate or worse	20
Severe or worse	10
Very severe	2

Notes
[10] - Subjects who completed the trial. Note, subjects can appear in more than one category.

No statistical analyses for this end point

Secondary: Self-reported side effects (abdominal pain)

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End point title

Self-reported side effects (abdominal pain)

End point description

Self-reporting of side effects was done via the digital diary, with each type of side effect scored on a visual analogue scale (VAS) from 0-100 (positive integers). This endpoint categorises self-reported abdominal pain side effects ever reported as mild or worse (over 0 on the VAS), moderate or worse (over 25 on the VAS), severe or worse (over 75 on the VAS), or very severe (over 75 on the VAS).

End point type

Secondary

End point timeframe

From baseline to the end of the trial (Week 14)

End point values	Intervention
Number of subjects analysed	196 ^[11]
Units: Positive integer
Mild or worse	48
Moderate or worse	20
Severe or worse	6
Very severe	2

Notes
[11] - Subjects who completed the trial. Note, subjects can appear in more than one category.

No statistical analyses for this end point

Secondary: Self-reported side effects (fatigue or drowsiness)

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End point title

Self-reported side effects (fatigue or drowsiness)

End point description

Self-reporting of side effects was done via the digital diary, with each type of side effect scored on a visual analogue scale (VAS) from 0-100 (positive integers). This endpoint categorises self-reported fatigue or drowsiness side effects ever reported as mild or worse (over 0 on the VAS), moderate or worse (over 25 on the VAS), severe or worse (over 75 on the VAS), or very severe (over 75 on the VAS).

End point type

Secondary

End point timeframe

From baseline to the end of the trial (Week 14)

End point values	Intervention
Number of subjects analysed	196 ^[12]
Units: Positive integer
Mild or worse	122
Moderate or worse	73
Severe or worse	37
Very severe	12

Notes
[12] - Subjects who completed the trial. Note, subjects can appear in more than one category.

No statistical analyses for this end point

Secondary: Self-reported side effects (nausea or vomiting)

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End point title

Self-reported side effects (nausea or vomiting)

End point description

Self-reporting of side effects was done via the digital diary, with each type of side effect scored on a visual analogue scale (VAS) from 0-100 (positive integers). This endpoint categorises self-reported nausea or vomiting side effects ever reported as mild or worse (over 0 on the VAS), moderate or worse (over 25 on the VAS), severe or worse (over 75 on the VAS), or very severe (over 75 on the VAS).

End point type

Secondary

End point timeframe

From baseline to the end of the trial (Week 14)

End point values	Intervention
Number of subjects analysed	196 ^[13]
Units: Positive integer
Mild or worse	61
Moderate or worse	26
Severe or worse	11
Very severe	5

Notes
[13] - Subjects who completed the trial. Note, subjects can appear in more than one category.

No statistical analyses for this end point

Secondary: Number of adverse events at least possibly related to trial medication (amlodipine)

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End point title

Number of adverse events at least possibly related to trial medication (amlodipine)

End point description

The number of adverse events reported during the trial that were said to be at least possibly related to amlodipine.

End point type

Secondary

End point timeframe

Within the trial follow-up period, from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	205
Units: Positive integer	377

No statistical analyses for this end point

Secondary: Number of subjects with reported adverse events at least possibly related to trial medication (amlodipine)

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End point title

Number of subjects with reported adverse events at least possibly related to trial medication (amlodipine)

End point description

The number of subjects with adverse events reported during the trial that were said to be at least possibly related to amlodipine.

End point type

Secondary

End point timeframe

Within the trial follow-up period, from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	196
Units: Positive integer	137

No statistical analyses for this end point

Secondary: Achieving blood pressure target at the end of treatment having experienced unwanted side effects from amlodipine

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End point title

Achieving blood pressure target at the end of treatment having experienced unwanted side effects from amlodipine

End point description

Number of subjects who achieved the blood pressure target of SBP<135 and DBP<85 mmHg at the end of the trial (Week 14) having also ever experienced an unwanted side effect scored over 25 on the 0-100 VAS in the digital diary between baseline and the end of the trial (Week 14).

End point type

Secondary

End point timeframe

Blood pressure at the end of the trial (Week 14) and reporting of unwanted side effect during follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[14]
Units: Positive integer
Any of the main 6 side effects	82
Headache	57
Swelling	35
Skin reaction	27
Abdominal pain	23
Fatigue or drowsiness	60
Nausea or vomiting	27

Notes
[14] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Achieving blood pressure target at the end of treatment without having experienced unwanted side effects from amlodipine

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End point title

Achieving blood pressure target at the end of treatment without having experienced unwanted side effects from amlodipine

End point description

Number of subjects who achieved the blood pressure target of SBP<135 and DBP<85 mmHg at the end of the trial (Week 14) having never experienced an unwanted side effect scored over 25 on the 0-100 VAS in the digital diary between baseline and the end of the trial (Week 14).

End point type

Secondary

End point timeframe

Blood pressure at the end of the trial (Week 14) and reporting of unwanted side effect during follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[15]
Units: Positive integer
Any of the 6 main side effects	20
Headache	45
Swelling	67
Skin reaction	75
Abdominal pain	79
Fatigue or drowsiness	42
Nausea or vomiting	75

Notes
[15] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Achieving combination of blood pressure target and response at the end of treatment having experienced unwanted side effects from amlodipine

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End point title

Achieving combination of blood pressure target and response at the end of treatment having experienced unwanted side effects from amlodipine

End point description

Number of subjects who achieved the combination of blood pressure target SBP<135 and DBP<85 mmHg at the end of the trial (Week 14), a reduction in SBP ≥10mmHg and a reduction in DBP ≥5mmHg from baseline to the end of the trial (Week 14), having also ever experienced an unwanted side effect scored over 25 on the 0-100 VAS in the digital diary between baseline and the end of the trial (Week 14).

End point type

Secondary

End point timeframe

Blood pressure at the end of the trial (Week 14) and reporting of unwanted side effect during follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[16]
Units: Positive integer
Any of the 6 main side effects	39
Headache	28
Swelling	17
Skin reaction	14
Abdominal pain	12
Fatigue or drowsiness	31
Nausea or vomiting	15

Notes
[16] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Achieving combination of blood pressure target and response at the end of treatment without having experienced unwanted side effects from amlodipine

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End point title

Achieving combination of blood pressure target and response at the end of treatment without having experienced unwanted side effects from amlodipine

End point description

Number of subjects who achieved the combination of blood pressure target SBP<135 and DBP<85 mmHg at the end of the trial (Week 14), a reduction in SBP ≥10mmHg and a reduction in DBP ≥5mmHg from baseline to the end of the trial (Week 14), having never experienced an unwanted side effect scored over 25 on the 0-100 VAS in the digital diary between baseline and the end of the trial (Week 14).

End point type

Secondary

End point timeframe

Blood pressure at the end of the trial (Week 14) and reporting of unwanted side effect during follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[17]
Units: Positive integer
Any of the 6 main side effects	14
Headache	25
Swelling	36
Skin reaction	39
Abdominal pain	41
Fatigue or drowsiness	22
Nausea or vomiting	38

Notes
[17] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Achieving blood pressure target at the end of treatment having experienced an adverse event at least possibly related to amlodipine

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End point title

Achieving blood pressure target at the end of treatment having experienced an adverse event at least possibly related to amlodipine

End point description

Number of subjects who achieved the blood pressure target of SBP<135 and DBP<85 mmHg at the end of the trial (Week 14) having also experienced an adverse event that was said to be at least possibly related to amlodipine between baseline and the end of the trial (Week 14).

End point type

Secondary

End point timeframe

Blood pressure at the end of the trial (Week 14) and reporting of unwanted side effect during follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[18]
Units: Positive integer	58

Notes
[18] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Achieving blood pressure target at the end of treatment having not experienced an adverse event at least possibly related to amlodipine

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End point title

Achieving blood pressure target at the end of treatment having not experienced an adverse event at least possibly related to amlodipine

End point description

Number of subjects who achieved the blood pressure target of SBP<135 and DBP<85 mmHg at the end of the trial (Week 14) having not experienced an adverse event that was said to be at least possibly related to amlodipine between baseline and the end of the trial (Week 14).

End point type

Secondary

End point timeframe

Blood pressure at the end of the trial (Week 14) and reporting of unwanted side effect during follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[19]
Units: Positive integer	44

Notes
[19] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Achieving combination of blood pressure target and reduction at the end of treatment having experienced an adverse event at least possibly related to amlodipine

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End point title

Achieving combination of blood pressure target and reduction at the end of treatment having experienced an adverse event at least possibly related to amlodipine

End point description

Number of subjects who achieved the combination blood pressure target of SBP<135 and DBP<85 mmHg at the end of the trial (Week 14), a reduction in SBP ≥10mmHg and a reduction in DBP ≥5mmHg from baseline to the end of the trial (Week 14), having experienced an adverse event that was said to be at least possibly related to amlodipine between baseline and the end of the trial (Week 14).

End point type

Secondary

End point timeframe

Blood pressure at the end of the trial (Week 14) and reporting of unwanted side effect during follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[20]
Units: Positive integer	25

Notes
[20] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Achieving combination blood pressure target and reduction at the end of treatment having not experienced an adverse event at least possibly related to amlodipine

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End point title

Achieving combination blood pressure target and reduction at the end of treatment having not experienced an adverse event at least possibly related to amlodipine

End point description

End point type

Secondary

End point timeframe

Blood pressure at the end of the trial (Week 14) and reporting of unwanted side effect during follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[21]
Units: Positive integer	28

Notes
[21] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Achieving blood pressure target at the end of treatment having experienced a dose-limiting side effect during the study

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End point title

Achieving blood pressure target at the end of treatment having experienced a dose-limiting side effect during the study

End point description

Number of subjects who achieved the blood pressure target of SBP<135 and DBP<85 mmHg at the end of the trial (Week 14) having also experienced a dose-limiting side effect between baseline and the end of the trial (Week 14). A subject is said to have experienced a dose-limiting side effect at a titration consultation if they: do not have a dose up-titration; are not already at the highest dose (10mg), have had a side effect recorded in the digital diary since last consultation of 25 or higher for any side effect, or have an AE that was deemed at least possibly related to amlodipine treatment since last consultation.

End point type

Secondary

End point timeframe

Blood pressure at the end of the trial (Week 14) and reporting of unwanted side effect or adverse event during follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[22]
Units: Positive integer	54

Notes
[22] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Achieving blood pressure target at the end of treatment having not experienced a dose-limiting side effect during the study

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End point title

Achieving blood pressure target at the end of treatment having not experienced a dose-limiting side effect during the study

End point description

Number of subjects who achieved the blood pressure target of SBP<135 and DBP<85 mmHg at the end of the trial (Week 14) having not experienced a dose-limiting side effect between baseline and the end of the trial (Week 14). A subject is said to have experienced a dose-limiting side effect at a titration consultation if they: do not have a dose up-titration; are not already at the highest dose (10mg), have had a side effect recorded in the digital diary since last consultation of 25 or higher for any side effect, or have an AE that was deemed at least possibly related to amlodipine treatment since last consultation.

End point type

Secondary

End point timeframe

Blood pressure at the end of the trial (Week 14) and reporting of unwanted side effect or adverse event during follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[23]
Units: Positive integer	48

Notes
[23] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Achieving combination blood pressure target and reduction at the end of treatment having experienced a dose-limiting side effect during the study

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End point title

Achieving combination blood pressure target and reduction at the end of treatment having experienced a dose-limiting side effect during the study

End point description

Number of subjects who achieved the combination blood pressure target of SBP<135 and DBP<85 mmHg at the end of the trial (Week 14), a reduction in SBP ≥10mmHg and a reduction in DBP ≥5mmHg from baseline to the end of the trial (Week 14), having also experienced a dose-limiting side effect between baseline and the end of the trial (Week 14). A subject is said to have experienced a dose-limiting side effect at a titration consultation if they: do not have a dose up-titration; are not already at the highest dose (10mg), have had a side effect recorded in the digital diary since last consultation of 25 or higher for any side effect, or have an AE that was deemed at least possibly related to amlodipine treatment since last consultation.

End point type

Secondary

End point timeframe

Blood pressure at the end of the trial (Week 14) and reporting of unwanted side effect or adverse event during follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[24]
Units: Positive integer	27

Notes
[24] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Achieving combination blood pressure target and reduction at the end of treatment having not experienced a dose-limiting side effect during the study

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End point title

Achieving combination blood pressure target and reduction at the end of treatment having not experienced a dose-limiting side effect during the study

End point description

Number of subjects who achieved the combination blood pressure target of SBP<135 and DBP<85 mmHg at the end of the trial (Week 14), a reduction in SBP ≥10mmHg and a reduction in DBP ≥5mmHg from baseline to the end of the trial (Week 14), having not experienced a dose-limiting side effect between baseline and the end of the trial (Week 14). A subject is said to have experienced a dose-limiting side effect at a titration consultation if they: do not have a dose up-titration; are not already at the highest dose (10mg), have had a side effect recorded in the digital diary since last consultation of 25 or higher for any side effect, or have an AE that was deemed at least possibly related to amlodipine treatment since last consultation.

End point type

Secondary

End point timeframe

Blood pressure at the end of the trial (Week 14) and reporting of unwanted side effect or adverse event during follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[25]
Units: Positive integer	26

Notes
[25] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Experiencing a dose-limiting side effect

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End point title

Experiencing a dose-limiting side effect

End point description

The number of patients who experience a dose-limiting side effect. A subject is said to have experienced a dose-limiting side effect at a titration consultation if they: do not have a dose up-titration; are not already at the highest dose (10mg), have had a side effect recorded in the digital diary since last consultation of 25 or higher for any side effect, or have an AE that was deemed at least possibly related to amlodipine treatment since last consultation.

End point type

Secondary

End point timeframe

The reporting of unwanted side effect or adverse event during follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[26]
Units: Positive integer	112

Notes
[26] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Number experiencing either unwanted side effect or an AE at least possibly related to amlodipine

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End point title

Number experiencing either unwanted side effect or an AE at least possibly related to amlodipine

End point description

The number of patients who experience either unwanted side effect or an AE at least possibly related to amlodipine.

End point type

Secondary

End point timeframe

The reporting of unwanted side effect or adverse event at least possibly related to amlodipine during follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[27]
Units: Positive integer	144

Notes
[27] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Achieving target of SBP<135 and DBP<85 mmHg at the end of treatment and experiencing either unwanted side effect or an AE at least possibly related to amlodipine

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End point title

Achieving target of SBP<135 and DBP<85 mmHg at the end of treatment and experiencing either unwanted side effect or an AE at least possibly related to amlodipine

End point description

Achieving target of SBP<135 and DBP<85 mmHg at the end of treatment and experiencing either unwanted side effect or an AE at least possibly related to amlodipine.

End point type

Secondary

End point timeframe

The reporting of unwanted side effect or adverse event during follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[28]
Units: Positive integer	70

Notes
[28] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Achieving target of SBP<135 and DBP<85 mmHg at the end of treatment and not experiencing either unwanted side effect or an AE at least possibly related to amlodipine

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End point title

Achieving target of SBP<135 and DBP<85 mmHg at the end of treatment and not experiencing either unwanted side effect or an AE at least possibly related to amlodipine

End point description

Achieving target of SBP<135 and DBP<85 mmHg at the end of treatment and not experiencing either unwanted side effect or an AE at least possibly related to amlodipine

End point type

Secondary

End point timeframe

The reporting of unwanted side effect or adverse event during follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[29]
Units: Positive integer	32

Notes
[29] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Achieving target combination of SBP<135 and DBP<85 mmHg at the end of treatment, a reduction in SBP ≥10mmHg and a reduction in DBP ≥5mmHg from baseline to the end of treatment and experiencing either unwanted side effect or an AE at least possibly related

Top of page

End point title

Achieving target combination of SBP<135 and DBP<85 mmHg at the end of treatment, a reduction in SBP ≥10mmHg and a reduction in DBP ≥5mmHg from baseline to the end of treatment and experiencing either unwanted side effect or an AE at least possibly related

End point description

End point type

Secondary

End point timeframe

The reporting of unwanted side effect or adverse event during follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[30]
Units: Positive integer	34

Notes
[30] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Achieving target combination of SBP<135 and DBP<85 mmHg at the end of treatment, a reduction in SBP ≥10mmHg and a reduction in DBP ≥5mmHg from baseline to the end of treatment and not experiencing either unwanted side effect or an AE at least possibly rel

Top of page

End point title

Achieving target combination of SBP<135 and DBP<85 mmHg at the end of treatment, a reduction in SBP ≥10mmHg and a reduction in DBP ≥5mmHg from baseline to the end of treatment and not experiencing either unwanted side effect or an AE at least possibly rel

End point description

End point type

Secondary

End point timeframe

The reporting of unwanted side effect or adverse event during follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[31]
Units: Positive integer	19

Notes
[31] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Number reporting taking amlodipine on 80% or more days of follow-up

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End point title

Number reporting taking amlodipine on 80% or more days of follow-up

End point description

Number reporting taking amlodipine on 80% or more days of follow-up.

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[32]
Units: Positive integer	180

Notes
[32] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Number reporting taking amlodipine on 80% or more days of follow-up and achieving the combination of target of SBP<135 and DBP<85 mmHg and a reduction in SBP ≥10mmHg and a reduction in DBP ≥5mmHg at the EOT

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End point title

Number reporting taking amlodipine on 80% or more days of follow-up and achieving the combination of target of SBP<135 and DBP<85 mmHg and a reduction in SBP ≥10mmHg and a reduction in DBP ≥5mmHg at the EOT

End point description

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[33]
Units: Positive integer	51

Notes
[33] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Number reporting taking amlodipine on 80% or more days of follow-up and NOT achieving the combination of target of SBP<135 and DBP<85, a reduction in SBP ≥10mmHg, and a reduction in DBP ≥5mmHg at the EOT

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End point title

Number reporting taking amlodipine on 80% or more days of follow-up and NOT achieving the combination of target of SBP<135 and DBP<85, a reduction in SBP ≥10mmHg, and a reduction in DBP ≥5mmHg at the EOT

End point description

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[34]
Units: Positive integer	129

Notes
[34] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Reduction in SBP ≥5mmHg from baseline to the end of treatment & experiencing any unwanted side effects from amlodipine (reporting any of the 6 main side effects 25 or over on the VAS)

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End point title

Reduction in SBP ≥5mmHg from baseline to the end of treatment & experiencing any unwanted side effects from amlodipine (reporting any of the 6 main side effects 25 or over on the VAS)

End point description

Reduction in SBP ≥5mmHg from baseline to the end of treatment & experiencing any unwanted side effects from amlodipine (reporting any of the 6 main side effects 25 or over on the VAS)

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[35]
Units: Positive integer	79

Notes
[35] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Reduction in SBP ≥5mmHg from baseline to the end of treatment & without experiencing any unwanted side effects from amlodipine (reporting any of the 6 main side effects 25 or over on the VAS)

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End point title

Reduction in SBP ≥5mmHg from baseline to the end of treatment & without experiencing any unwanted side effects from amlodipine (reporting any of the 6 main side effects 25 or over on the VAS)

End point description

Reduction in SBP ≥5mmHg from baseline to the end of treatment & without experiencing any unwanted side effects from amlodipine (reporting any of the 6 main side effects 25 or over on the VAS)

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[36]
Units: Positive integer	57

Notes
[36] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Reduction in SBP ≥5mmHg from baseline to the end of treatment & experiencing a dose-limiting side effects from amlodipine

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End point title

Reduction in SBP ≥5mmHg from baseline to the end of treatment & experiencing a dose-limiting side effects from amlodipine

End point description

Reduction in SBP ≥5mmHg from baseline to the end of treatment & experiencing a dose-limiting side effects from amlodipine

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[37]
Units: Positive integer	78

Notes
[37] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Reduction in SBP ≥5mmHg from baseline to the end of treatment & without experiencing a dose-limiting side effects from amlodipine

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End point title

Reduction in SBP ≥5mmHg from baseline to the end of treatment & without experiencing a dose-limiting side effects from amlodipine

End point description

Reduction in SBP ≥5mmHg from baseline to the end of treatment & without experiencing a dose-limiting side effects from amlodipine

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[38]
Units: Positive integer	58

Notes
[38] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Reduction in SBP ≥5mmHg from baseline to the end of treatment & experiencing an AE at least possibly related to amlodipine

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End point title

Reduction in SBP ≥5mmHg from baseline to the end of treatment & experiencing an AE at least possibly related to amlodipine

End point description

Reduction in SBP ≥5mmHg from baseline to the end of treatment & experiencing an AE at least possibly related to amlodipine

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[39]
Units: Positive integer	84

Notes
[39] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Reduction in SBP ≥5mmHg from baseline to the end of treatment & without experiencing an AE at least possibly related to amlodipine

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End point title

Reduction in SBP ≥5mmHg from baseline to the end of treatment & without experiencing an AE at least possibly related to amlodipine

End point description

Reduction in SBP ≥5mmHg from baseline to the end of treatment & without experiencing an AE at least possibly related to amlodipine

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[40]
Units: Positive integer	52

Notes
[40] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Reduction in SBP ≥10mmHg from baseline to the end of treatment & experiencing any unwanted side effects from amlodipine (reporting any of the 6 main side effects 25 or over on the VAS)

Top of page

End point title

Reduction in SBP ≥10mmHg from baseline to the end of treatment & experiencing any unwanted side effects from amlodipine (reporting any of the 6 main side effects 25 or over on the VAS)

End point description

Reduction in SBP ≥10mmHg from baseline to the end of treatment & experiencing any unwanted side effects from amlodipine (reporting any of the 6 main side effects 25 or over on the VAS)

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[41]
Units: Positive integer	56

Notes
[41] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Reduction in SBP ≥10mmHg from baseline to the end of treatment & without experiencing any unwanted side effects from amlodipine (reporting any of the 6 main side effects 25 or over on the VAS)

Top of page

End point title

Reduction in SBP ≥10mmHg from baseline to the end of treatment & without experiencing any unwanted side effects from amlodipine (reporting any of the 6 main side effects 25 or over on the VAS)

End point description

Reduction in SBP ≥10mmHg from baseline to the end of treatment & without experiencing any unwanted side effects from amlodipine (reporting any of the 6 main side effects 25 or over on the VAS)

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[42]
Units: Positive integer	42

Notes
[42] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Reduction in SBP ≥10mmHg from baseline to the end of treatment & experiencing a dose-limiting side effects from amlodipine

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End point title

Reduction in SBP ≥10mmHg from baseline to the end of treatment & experiencing a dose-limiting side effects from amlodipine

End point description

Reduction in SBP ≥10mmHg from baseline to the end of treatment & experiencing a dose-limiting side effects from amlodipine

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[43]
Units: Positive integer	59

Notes
[43] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Reduction in SBP ≥10mmHg from baseline to the end of treatment & without experiencing a dose-limiting side effects from amlodipine

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End point title

Reduction in SBP ≥10mmHg from baseline to the end of treatment & without experiencing a dose-limiting side effects from amlodipine

End point description

Reduction in SBP ≥10mmHg from baseline to the end of treatment & without experiencing a dose-limiting side effects from amlodipine

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[44]
Units: Positive integer	39

Notes
[44] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Reduction in SBP ≥10mmHg from baseline to the end of treatment & experiencing an AE at least possibly related to amlodipine

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End point title

Reduction in SBP ≥10mmHg from baseline to the end of treatment & experiencing an AE at least possibly related to amlodipine

End point description

Reduction in SBP ≥10mmHg from baseline to the end of treatment & experiencing an AE at least possibly related to amlodipine

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[45]
Units: Positive integer	58

Notes
[45] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Reduction in SBP ≥10mmHg from baseline to the end of treatment & without experiencing an AE at least possibly related to amlodipine

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End point title

Reduction in SBP ≥10mmHg from baseline to the end of treatment & without experiencing an AE at least possibly related to amlodipine

End point description

Reduction in SBP ≥10mmHg from baseline to the end of treatment & without experiencing an AE at least possibly related to amlodipine

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[46]
Units: Positive integer	40

Notes
[46] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Reduction in DBP ≥5mmHg from baseline to the end of treatment & experiencing any unwanted side effects from amlodipine (reporting any of the 6 main side effects 25 or over on the VAS)

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End point title

Reduction in DBP ≥5mmHg from baseline to the end of treatment & experiencing any unwanted side effects from amlodipine (reporting any of the 6 main side effects 25 or over on the VAS)

End point description

Reduction in DBP ≥5mmHg from baseline to the end of treatment & experiencing any unwanted side effects from amlodipine (reporting any of the 6 main side effects 25 or over on the VAS)

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[47]
Units: Positive integer	62

Notes
[47] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Reduction in DBP ≥5mmHg from baseline to the end of treatment & without experiencing any unwanted side effects from amlodipine (reporting any of the 6 main side effects 25 or over on the VAS)

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End point title

Reduction in DBP ≥5mmHg from baseline to the end of treatment & without experiencing any unwanted side effects from amlodipine (reporting any of the 6 main side effects 25 or over on the VAS)

End point description

Reduction in DBP ≥5mmHg from baseline to the end of treatment & without experiencing any unwanted side effects from amlodipine (reporting any of the 6 main side effects 25 or over on the VAS)

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[48]
Units: Positive integer	50

Notes
[48] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Reduction in DBP ≥5mmHg from baseline to the end of treatment & experiencing a dose-limiting side effects from amlodipine

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End point title

Reduction in DBP ≥5mmHg from baseline to the end of treatment & experiencing a dose-limiting side effects from amlodipine

End point description

Reduction in DBP ≥5mmHg from baseline to the end of treatment & experiencing a dose-limiting side effects from amlodipine

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[49]
Units: Positive integer	61

Notes
[49] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Reduction in DBP ≥5mmHg from baseline to the end of treatment & without experiencing a dose-limiting side effects from amlodipine

Top of page

End point title

Reduction in DBP ≥5mmHg from baseline to the end of treatment & without experiencing a dose-limiting side effects from amlodipine

End point description

Reduction in DBP ≥5mmHg from baseline to the end of treatment & without experiencing a dose-limiting side effects from amlodipine

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[50]
Units: Positive integer	52

Notes
[50] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Reduction in DBP ≥5mmHg from baseline to the end of treatment & experiencing an AE at least possibly related to amlodipine

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End point title

Reduction in DBP ≥5mmHg from baseline to the end of treatment & experiencing an AE at least possibly related to amlodipine

End point description

Reduction in DBP ≥5mmHg from baseline to the end of treatment & experiencing an AE at least possibly related to amlodipine

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[51]
Units: Positive integer	65

Notes
[51] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Reduction in DBP ≥5mmHg from baseline to the end of treatment & without experiencing an AE at least possibly related to amlodipine

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End point title

Reduction in DBP ≥5mmHg from baseline to the end of treatment & without experiencing an AE at least possibly related to amlodipine

End point description

Reduction in DBP ≥5mmHg from baseline to the end of treatment & without experiencing an AE at least possibly related to amlodipine

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	189 ^[52]
Units: Positive integer	47

Notes
[52] - Subjects who completed the trial and had at least 1 BP measurement at the end of the trial.

No statistical analyses for this end point

Secondary: Number making any diary entry on 80% or more days

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End point title

Number making any diary entry on 80% or more days

End point description

Number making any diary entry on 80% or more days.

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	196 ^[53]
Units: Positive integer	187

Notes
[53] - Subjects who completed the trial.

No statistical analyses for this end point

Secondary: Number making a BP diary entry on 80% or more occasions

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End point title

Number making a BP diary entry on 80% or more occasions

End point description

Number making a BP diary entry on 80% or more occasions. Patients were asked to record BP both AM and PM, and adherence for BP as calculated based on these 2 distinct occasions.

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	196 ^[54]
Units: Positive integer	164

Notes
[54] - Subjects who completed the trial.

No statistical analyses for this end point

Secondary: Number making a BP and side effect diary entry on 80% or more days

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End point title

Number making a BP and side effect diary entry on 80% or more days

End point description

Number making a BP and side effect diary entry on 80% or more days. Patients were asked to record BP both AM and PM, and adherence for BP as calculated based on these 2 distinct occasions.

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the trial (Week 14).

End point values	Intervention
Number of subjects analysed	196 ^[55]
Units: Positive integer	155

Notes
[55] - Subjects who completed the trial.

No statistical analyses for this end point

Secondary: Number achieving reduction in SBP of ≥5mmHg at the end of the study

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End point title

Number achieving reduction in SBP of ≥5mmHg at the end of the study

End point description

Number achieving reduction in SBP of ≥5mmHg at the end of the study.

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the study (3 months).

End point values	Observation
Number of subjects analysed	123 ^[56]
Units: Positive integer	34

Notes
[56] - Subjects who completed the trial and had at least 1 BP measurement at the end of the study.

No statistical analyses for this end point

Secondary: Number achieving reduction in SBP of ≥10mmHg at the end of the study

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End point title

Number achieving reduction in SBP of ≥10mmHg at the end of the study

End point description

Number achieving reduction in SBP of ≥10mmHg at the end of the study.

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the study (3 months).

End point values	Observation
Number of subjects analysed	123 ^[57]
Units: Positive integer	10

Notes
[57] - Subjects who completed the trial and had at least 1 BP measurement at the end of the study.

No statistical analyses for this end point

Secondary: Number achieving reduction in DBP of ≥5mmHg at the end of the study

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End point title

Number achieving reduction in DBP of ≥5mmHg at the end of the study

End point description

Number achieving reduction in DBP of ≥5mmHg at the end of the study.

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the study (3 months).

End point values	Observation
Number of subjects analysed	123 ^[58]
Units: Positive integer	18

Notes
[58] - Subjects who completed the trial and had at least 1 BP measurement at the end of the study.

No statistical analyses for this end point

Secondary: Patients who presented with uncontrolled BP (SBP≥135 or DBP≥85 mmHg) during the study

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End point title

Patients who presented with uncontrolled BP (SBP≥135 or DBP≥85 mmHg) during the study

End point description

Patients who presented with uncontrolled BP (SBP≥135 or DBP≥85 mmHg) during the study.

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the study (3 months).

End point values	Observation
Number of subjects analysed	138 ^[59]
Units: Positive integer	24

Notes
[59] - Participants with BP readings and either completed or crossed over into intervention cohort.

No statistical analyses for this end point

Secondary: Patients who did not present with uncontrolled BP during the study, and had moderate BP control at the end of the study (SBP≥120 and SBP<135 or DBP≥80 mmHg and DBP<85)

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End point title

Patients who did not present with uncontrolled BP during the study, and had moderate BP control at the end of the study (SBP≥120 and SBP<135 or DBP≥80 mmHg and DBP<85)

End point description

Patients who did not present with uncontrolled BP during the study, and had moderate BP control at the end of the study (SBP≥120 and SBP<135 or DBP≥80 mmHg and DBP<85)

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the study (3 months).

End point values	Observation
Number of subjects analysed	138 ^[60]
Units: Positive integer	82

Notes
[60] - Participants with BP readings and either completed or crossed over into intervention cohort.

No statistical analyses for this end point

Secondary: Patients who did not present with uncontrolled BP during the study, and had good BP control at the end of the study (SBP<120 and DBP<80 mmHg)

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End point title

Patients who did not present with uncontrolled BP during the study, and had good BP control at the end of the study (SBP<120 and DBP<80 mmHg)

End point description

Patients who did not present with uncontrolled BP during the study, and had good BP control at the end of the study (SBP<120 and DBP<80 mmHg).

End point type

Secondary

End point timeframe

During follow-up from baseline to the end of the study (3 months).

End point values	Observation
Number of subjects analysed	138 ^[61]
Units: Positive integer	32

Notes
[61] - Participants with BP readings and either completed or crossed over into intervention cohort.

No statistical analyses for this end point

Other pre-specified: Number of adverse events

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End point title

Number of adverse events

End point description

The number of adverse events reported during the trial for each trial arm.

End point type

Other pre-specified

End point timeframe

Within the trial follow-up period, from baseline to the end of the trial (Week 14 for the intervention arm, and Month 3 for the observation arm).

End point values	Intervention	Observation
Number of subjects analysed	205	162
Units: Positive integer	469	28

No statistical analyses for this end point

Other pre-specified: Number of subjects with reported adverse event

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End point title

Number of subjects with reported adverse event

End point description

The number of subjects with adverse events reported during the trial for each trial arm.

End point type

Other pre-specified

End point timeframe

Within the trial follow-up period, from baseline to the end of the trial (Week 14 for the intervention arm, and Month 3 for the observation arm).

End point values	Intervention	Observation
Number of subjects analysed	205	162
Units: Positive integer	154	22

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse events were collected from screening (when the electronic diary was uploaded by the participant) until the End of Treatment visit (or end of study visit for the observation cohort).

Adverse event reporting additional description

Adverse events were collected by daily reporting on the electronic diary uploaded onto participant's smartphones, which informed the regular study calls from trails team staff at weekly/every two weeks frequency for the intervention group and monthly for the observation group). Diary for intervention pts encouraged reporting of AE's.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.119

Reporting group title

Intervention Group

Reporting group description

Subjects with uncontrolled blood pressure at baseline were allocated to intervention and given small doses of amlodipine in addition to existing therapy at baseline.

Reporting group title

Observation study

Reporting group description

subjects with controlled blood pressure were assigned to the observational group and were assigned to stay on baseline medication and be followed up for 3 months.

Serious adverse events	Intervention Group	Observation study
Total subjects affected by serious adverse events
subjects affected / exposed	5 / 205 (2.44%)	1 / 162 (0.62%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast tumour malignant
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Malignant melanoma
subjects affected / exposed	0 / 205 (0.00%)	1 / 162 (0.62%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Unstable Angina
subjects affected / exposed	2 / 205 (0.98%)	0 / 162 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
STEMI
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Nephrotic syndrome
Additional description: New diagnosis during study
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 1%

Non-serious adverse events	Intervention Group	Observation study
Total subjects affected by non serious adverse events
subjects affected / exposed	154 / 205 (75.12%)	22 / 162 (13.58%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
subjects affected / exposed	0 / 205 (0.00%)	1 / 162 (0.62%)
occurrences all number	0	1
Vascular disorders
Flushing
subjects affected / exposed	2 / 205 (0.98%)	0 / 162 (0.00%)
occurrences all number	2	0
Hypotension
subjects affected / exposed	2 / 205 (0.98%)	0 / 162 (0.00%)
occurrences all number	2	0
Surgical and medical procedures
Cataract operation
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	6 / 205 (2.93%)	0 / 162 (0.00%)
occurrences all number	6	0
Chest discomfort
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Chest pain
subjects affected / exposed	0 / 205 (0.00%)	1 / 162 (0.62%)
occurrences all number	0	1
Fatigue
subjects affected / exposed	75 / 205 (36.59%)	2 / 162 (1.23%)
occurrences all number	78	2
Feeling abnormal
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Gait disturbance
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Influenza like illness
subjects affected / exposed	13 / 205 (6.34%)	0 / 162 (0.00%)
occurrences all number	14	0
Malaise
subjects affected / exposed	1 / 205 (0.49%)	1 / 162 (0.62%)
occurrences all number	1	1
Non-cardiac chest pain
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Oedema
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Oedema peripheral
subjects affected / exposed	45 / 205 (21.95%)	0 / 162 (0.00%)
occurrences all number	46	0
Pain
subjects affected / exposed	3 / 205 (1.46%)	1 / 162 (0.62%)
occurrences all number	3	1
Peripheral swelling
subjects affected / exposed	2 / 205 (0.98%)	0 / 162 (0.00%)
occurrences all number	2	0
Sensation of foreign body
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Swelling
subjects affected / exposed	3 / 205 (1.46%)	0 / 162 (0.00%)
occurrences all number	3	0
Temperature intolerance
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Immune system disorders
Allergy to arthropod sting
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Hypersensitivity
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Seasonal allergy
subjects affected / exposed	3 / 205 (1.46%)	0 / 162 (0.00%)
occurrences all number	3	0
Reproductive system and breast disorders
Breast mass
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Erectile dysfunction
subjects affected / exposed	2 / 205 (0.98%)	0 / 162 (0.00%)
occurrences all number	2	0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 205 (0.00%)	1 / 162 (0.62%)
occurrences all number	0	1
Cough
subjects affected / exposed	3 / 205 (1.46%)	0 / 162 (0.00%)
occurrences all number	3	0
Dyspnoea
subjects affected / exposed	12 / 205 (5.85%)	0 / 162 (0.00%)
occurrences all number	12	0
Dyspnoea exertional
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Epistaxis
subjects affected / exposed	2 / 205 (0.98%)	0 / 162 (0.00%)
occurrences all number	2	0
Oropharyngeal pain
subjects affected / exposed	3 / 205 (1.46%)	0 / 162 (0.00%)
occurrences all number	3	0
Psychiatric disorders
Anxiety
subjects affected / exposed	2 / 205 (0.98%)	0 / 162 (0.00%)
occurrences all number	2	0
Depressed mood
subjects affected / exposed	0 / 205 (0.00%)	1 / 162 (0.62%)
occurrences all number	0	1
Insomnia
subjects affected / exposed	3 / 205 (1.46%)	0 / 162 (0.00%)
occurrences all number	3	0
Poor quality sleep
subjects affected / exposed	2 / 205 (0.98%)	0 / 162 (0.00%)
occurrences all number	2	0
Sleep disorder
subjects affected / exposed	3 / 205 (1.46%)	0 / 162 (0.00%)
occurrences all number	3	0
Investigations
Heart rate irregular
subjects affected / exposed	1 / 205 (0.49%)	1 / 162 (0.62%)
occurrences all number	1	1
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	2 / 205 (0.98%)	0 / 162 (0.00%)
occurrences all number	2	0
Muscle strain
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Cardiac disorders
Bradycardia
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Palpitations
subjects affected / exposed	6 / 205 (2.93%)	0 / 162 (0.00%)
occurrences all number	6	0
Nervous system disorders
Burning sensation
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Dizziness
subjects affected / exposed	11 / 205 (5.37%)	2 / 162 (1.23%)
occurrences all number	11	2
Dizziness postural
subjects affected / exposed	3 / 205 (1.46%)	1 / 162 (0.62%)
occurrences all number	3	1
Dysgeusia
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Headache
subjects affected / exposed	55 / 205 (26.83%)	1 / 162 (0.62%)
occurrences all number	59	1
Migraine
subjects affected / exposed	0 / 205 (0.00%)	1 / 162 (0.62%)
occurrences all number	0	1
Nerve compression
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Neuralgia
subjects affected / exposed	2 / 205 (0.98%)	0 / 162 (0.00%)
occurrences all number	2	0
Paraesthesia
subjects affected / exposed	2 / 205 (0.98%)	0 / 162 (0.00%)
occurrences all number	2	0
Presyncope
subjects affected / exposed	1 / 205 (0.49%)	1 / 162 (0.62%)
occurrences all number	1	1
Sciatica
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Sleep deficit
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Ear and labyrinth disorders
Tinnitus
subjects affected / exposed	2 / 205 (0.98%)	0 / 162 (0.00%)
occurrences all number	3	0
Vertigo
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Eye disorders
Dry eye
subjects affected / exposed	2 / 205 (0.98%)	0 / 162 (0.00%)
occurrences all number	2	0
Halo vision
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Vision blurred
subjects affected / exposed	2 / 205 (0.98%)	0 / 162 (0.00%)
occurrences all number	2	0
Visual impairment
subjects affected / exposed	5 / 205 (2.44%)	1 / 162 (0.62%)
occurrences all number	5	1
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Abdominal distension
subjects affected / exposed	3 / 205 (1.46%)	0 / 162 (0.00%)
occurrences all number	3	0
Abdominal pain
subjects affected / exposed	20 / 205 (9.76%)	0 / 162 (0.00%)
occurrences all number	23	0
Abdominal pain upper
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Abdominal rigidity
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Constipation
subjects affected / exposed	5 / 205 (2.44%)	0 / 162 (0.00%)
occurrences all number	5	0
Diarrhoea
subjects affected / exposed	6 / 205 (2.93%)	0 / 162 (0.00%)
occurrences all number	6	0
Dry mouth
subjects affected / exposed	4 / 205 (1.95%)	0 / 162 (0.00%)
occurrences all number	4	0
Dyspepsia
subjects affected / exposed	3 / 205 (1.46%)	0 / 162 (0.00%)
occurrences all number	3	0
Food poisoning
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Gastritis
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Large intestine polyp
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Nausea
subjects affected / exposed	19 / 205 (9.27%)	0 / 162 (0.00%)
occurrences all number	22	0
Paraesthesia oral
subjects affected / exposed	2 / 205 (0.98%)	0 / 162 (0.00%)
occurrences all number	2	0
Vomiting
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Skin and subcutaneous tissue disorders
Hyperhidrosis
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Pruritus
subjects affected / exposed	3 / 205 (1.46%)	0 / 162 (0.00%)
occurrences all number	3	0
Rash
subjects affected / exposed	7 / 205 (3.41%)	0 / 162 (0.00%)
occurrences all number	7	0
Skin reaction
subjects affected / exposed	13 / 205 (6.34%)	0 / 162 (0.00%)
occurrences all number	13	0
Renal and urinary disorders
Nocturia
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Pollakiuria
subjects affected / exposed	6 / 205 (2.93%)	0 / 162 (0.00%)
occurrences all number	6	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	14 / 205 (6.83%)	0 / 162 (0.00%)
occurrences all number	14	0
Arthritis
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Back pain
subjects affected / exposed	7 / 205 (3.41%)	0 / 162 (0.00%)
occurrences all number	7	0
Costochondritis
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Fibromyalgia
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Joint swelling
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Limb discomfort
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Muscle spasms
subjects affected / exposed	4 / 205 (1.95%)	0 / 162 (0.00%)
occurrences all number	4	0
Myalgia
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Neck pain
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Pain in extremity
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Infections and infestations
Acute pulmonary histoplasmosis
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
COVID-19
subjects affected / exposed	1 / 205 (0.49%)	3 / 162 (1.85%)
occurrences all number	1	3
Diverticulitis
subjects affected / exposed	0 / 205 (0.00%)	1 / 162 (0.62%)
occurrences all number	0	1
Ear infection
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Folliculitis
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Gastroenteritis
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Influenza
subjects affected / exposed	1 / 205 (0.49%)	1 / 162 (0.62%)
occurrences all number	1	1
Labyrinthitis
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Lower respiratory tract infection
subjects affected / exposed	1 / 205 (0.49%)	2 / 162 (1.23%)
occurrences all number	1	2
Nasopharyngitis
subjects affected / exposed	2 / 205 (0.98%)	3 / 162 (1.85%)
occurrences all number	2	3
Tonsillitis
subjects affected / exposed	0 / 205 (0.00%)	1 / 162 (0.62%)
occurrences all number	0	1
Tooth infection
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Urinary tract infection bacterial
subjects affected / exposed	0 / 205 (0.00%)	1 / 162 (0.62%)
occurrences all number	0	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Dehydration
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Gout
subjects affected / exposed	3 / 205 (1.46%)	0 / 162 (0.00%)
occurrences all number	3	0
Hyperglycaemia
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0
Hypoglycaemia
subjects affected / exposed	1 / 205 (0.49%)	0 / 162 (0.00%)
occurrences all number	1	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

04 Jan 2021

SA01 The protocol, participant information sheet and consent form are updated to capture the following information. Post-screening visit, blood pressure is measured at home for 5 to 7 days, this is changed to "at least 7 days" to make it consistent with international expectations for home blood pressure studies. The minimum number of blood pressure readings required (24) is unchanged. Blood pressure criteria for entry into the Intervention part of the study are reduced to 135mmHg or above and/or 85mmHg and above, making the entry criteria consistent with international blood pressure guidelines. These changes are following expert feedback from the Trial Steering Committee (notably Professors McManus, Oxford and Poulter, Imperial). This may increase the proportion of participants who will be eligible for active added blood pressure treatment during the study, and also lowers the threshold for participants who are in the observational part of the study, but whose blood pressure might be improved by additional treatment (for safety participants can cross back into intervention if their blood pressure measurements become uncontrolled during the study). Permission is sought to transport IMP at room-temperature (then use within 3 months stored 2-8 in a refrigerator) rather than cold chain upright conditions, as advice from the manufacturer (Rosemont Pharmaceuticals) is that temperature stability data make this reasonable without loss of efficacy. During the COVID-19 pandemic cold-chain transport is at a premium and practical difficulties such as late deliveries have inconvenienced some participants. Where intolerance of small dose amlodipine occurs, smaller dose increments of 0.25mg and 0.5mg amlodipine may be used, where current or past intolerance makes this fit the patients need. A new statistician has joined the study delivery team, along with an administrative change of site telephone contact number for participants.

05 Mar 2021

SA02 Amendment is to add two further Participant Identifier Centre (PIC Site), to identify participants. The current existing PIC Sites are Barts NHS Health Trust and Salford NHS Trust. The third site is named as Wokingham Medical Practice, the fourth as The Homerton University Hospital. We are also updating an email contact address only in the Privacy Policy. We are also updating the consenting procedure and documentation of this to make this more robust: requesting to change change initial consent to not be conducted by a medically qualified person, this will be taken by site research staff, and we have updated the consent form to include a 2nd statement – of confirmation of consent at commencement of the intervention by a medically qualified person and must be completed whilst talking to the participant.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Sponsor audit May 2021 identified potential issues of data integrity, inaccuracies in the protocol and patient eligibility. None of these affected participant safety. A protocol amendment written but was not submitted in error.

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Clinical trials

Clinical Trial Results: Personalised Electronic Record Supported OptimisatioN when ALone for Patients with Hypertension- Pilot Study for Remote Medical Management of Hypertension During the COVID-19 Pandemic

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change in systolic blood pressure from baseline to the end of the trial (Week 14)

Primary: Change in systolic blood pressure from baseline to the end of the trial (Week 14)

Secondary: Change in diastolic blood pressure from baseline to the end of the trial (Week 14)

Secondary: Change in diastolic blood pressure from baseline to the end of the trial (Week 14)

Secondary: Achieving blood pressure target less than 135 mmHg systolic and less than 85 mmHg diastolic blood pressure at the end of the trial (Week 14)

Secondary: Achieving blood pressure target less than 135 mmHg systolic and less than 85 mmHg diastolic blood pressure at the end of the trial (Week 14)

Secondary: Achieving reduction of 5 or more mmHg systolic blood pressure by the end of the trial (Week 14)

Secondary: Achieving reduction of 5 or more mmHg systolic blood pressure by the end of the trial (Week 14)

Secondary: Achieving reduction of 10 or more mmHg systolic blood pressure by the end of the trial (Week 14)

Secondary: Achieving reduction of 10 or more mmHg systolic blood pressure by the end of the trial (Week 14)

Secondary: Achieving reduction of 5 or more mmHg diastolic blood pressure by the end of the trial (Week 14)

Secondary: Achieving reduction of 5 or more mmHg diastolic blood pressure by the end of the trial (Week 14)

Secondary: Achieving combination of target blood pressure & specified reductions in blood pressure by the end of the trial (Week 14)

Secondary: Achieving combination of target blood pressure & specified reductions in blood pressure by the end of the trial (Week 14)

Secondary: Median time to achieving blood pressure control

Secondary: Median time to achieving blood pressure control

Secondary: Self-reported side effects (Any of the main 6)

Secondary: Self-reported side effects (Any of the main 6)

Secondary: Self-reported side effects (headache)

Secondary: Self-reported side effects (headache)

Secondary: Self-reported side effects (swelling)

Secondary: Self-reported side effects (swelling)

Secondary: Self-reported side effects (skin reaction)

Secondary: Self-reported side effects (skin reaction)

Secondary: Self-reported side effects (abdominal pain)

Secondary: Self-reported side effects (abdominal pain)

Secondary: Self-reported side effects (fatigue or drowsiness)

Secondary: Self-reported side effects (fatigue or drowsiness)

Secondary: Self-reported side effects (nausea or vomiting)

Secondary: Self-reported side effects (nausea or vomiting)

Secondary: Number of adverse events at least possibly related to trial medication (amlodipine)

Secondary: Number of adverse events at least possibly related to trial medication (amlodipine)

Secondary: Number of subjects with reported adverse events at least possibly related to trial medication (amlodipine)

Secondary: Number of subjects with reported adverse events at least possibly related to trial medication (amlodipine)

Secondary: Achieving blood pressure target at the end of treatment having experienced unwanted side effects from amlodipine

Secondary: Achieving blood pressure target at the end of treatment having experienced unwanted side effects from amlodipine

Secondary: Achieving blood pressure target at the end of treatment without having experienced unwanted side effects from amlodipine

Secondary: Achieving blood pressure target at the end of treatment without having experienced unwanted side effects from amlodipine

Secondary: Achieving combination of blood pressure target and response at the end of treatment having experienced unwanted side effects from amlodipine

Secondary: Achieving combination of blood pressure target and response at the end of treatment having experienced unwanted side effects from amlodipine

Secondary: Achieving combination of blood pressure target and response at the end of treatment without having experienced unwanted side effects from amlodipine

Secondary: Achieving combination of blood pressure target and response at the end of treatment without having experienced unwanted side effects from amlodipine

Secondary: Achieving blood pressure target at the end of treatment having experienced an adverse event at least possibly related to amlodipine

Secondary: Achieving blood pressure target at the end of treatment having experienced an adverse event at least possibly related to amlodipine

Secondary: Achieving blood pressure target at the end of treatment having not experienced an adverse event at least possibly related to amlodipine

Secondary: Achieving blood pressure target at the end of treatment having not experienced an adverse event at least possibly related to amlodipine

Secondary: Achieving combination of blood pressure target and reduction at the end of treatment having experienced an adverse event at least possibly related to amlodipine

Secondary: Achieving combination of blood pressure target and reduction at the end of treatment having experienced an adverse event at least possibly related to amlodipine

Secondary: Achieving combination blood pressure target and reduction at the end of treatment having not experienced an adverse event at least possibly related to amlodipine

Secondary: Achieving combination blood pressure target and reduction at the end of treatment having not experienced an adverse event at least possibly related to amlodipine

Secondary: Achieving blood pressure target at the end of treatment having experienced a dose-limiting side effect during the study

Secondary: Achieving blood pressure target at the end of treatment having experienced a dose-limiting side effect during the study

Secondary: Achieving blood pressure target at the end of treatment having not experienced a dose-limiting side effect during the study

Secondary: Achieving blood pressure target at the end of treatment having not experienced a dose-limiting side effect during the study

Secondary: Achieving combination blood pressure target and reduction at the end of treatment having experienced a dose-limiting side effect during the study

Secondary: Achieving combination blood pressure target and reduction at the end of treatment having experienced a dose-limiting side effect during the study

Secondary: Achieving combination blood pressure target and reduction at the end of treatment having not experienced a dose-limiting side effect during the study

Secondary: Achieving combination blood pressure target and reduction at the end of treatment having not experienced a dose-limiting side effect during the study

Secondary: Experiencing a dose-limiting side effect

Secondary: Experiencing a dose-limiting side effect

Secondary: Number experiencing either unwanted side effect or an AE at least possibly related to amlodipine

Secondary: Number experiencing either unwanted side effect or an AE at least possibly related to amlodipine

Secondary: Achieving target of SBP<135 and DBP<85 mmHg at the end of treatment and experiencing either unwanted side effect or an AE at least possibly related to amlodipine

Secondary: Achieving target of SBP<135 and DBP<85 mmHg at the end of treatment and experiencing either unwanted side effect or an AE at least possibly related to amlodipine

Secondary: Achieving target of SBP<135 and DBP<85 mmHg at the end of treatment and not experiencing either unwanted side effect or an AE at least possibly related to amlodipine

Secondary: Achieving target of SBP<135 and DBP<85 mmHg at the end of treatment and not experiencing either unwanted side effect or an AE at least possibly related to amlodipine

Secondary: Achieving target combination of SBP<135 and DBP<85 mmHg at the end of treatment, a reduction in SBP ≥10mmHg and a reduction in DBP ≥5mmHg from baseline to the end of treatment and experiencing either unwanted side effect or an AE at least possibly related

Secondary: Achieving target combination of SBP<135 and DBP<85 mmHg at the end of treatment, a reduction in SBP ≥10mmHg and a reduction in DBP ≥5mmHg from baseline to the end of treatment and experiencing either unwanted side effect or an AE at least possibly related

Secondary: Achieving target combination of SBP<135 and DBP<85 mmHg at the end of treatment, a reduction in SBP ≥10mmHg and a reduction in DBP ≥5mmHg from baseline to the end of treatment and not experiencing either unwanted side effect or an AE at least possibly rel

Secondary: Achieving target combination of SBP<135 and DBP<85 mmHg at the end of treatment, a reduction in SBP ≥10mmHg and a reduction in DBP ≥5mmHg from baseline to the end of treatment and not experiencing either unwanted side effect or an AE at least possibly rel

Clinical Trial Results:
Personalised Electronic Record Supported OptimisatioN when ALone for Patients with Hypertension- Pilot Study for Remote Medical Management of Hypertension During the COVID-19 Pandemic