Clinical Trial Results:
Do ACE inhibitors reduce postural instability in older people?: Towards a novel approach to falls prevention.
Summary
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EudraCT number |
2013-001677-24 |
Trial protocol |
GB |
Global end of trial date |
30 Sep 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Nov 2016
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First version publication date |
17 Nov 2016
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
2012GR06
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Additional study identifiers
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ISRCTN number |
ISRCTN58995463 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
University of Dundee and NHS Tayside
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Sponsor organisation address |
Residency Block, Level 3, Ninewells Hospital, George Pirie, Dundee, United Kingdom, DD1 9SY
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Public contact |
Dr Deepa Sumukadas, University of Dundee, +44 01382 383086, d.sumukadas@dundee.ac.uk
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Scientific contact |
Dr Deepa Sumukadas, University of Dundee, +44 01382 383086, d.sumukadas@dundee.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
26 Oct 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Sep 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Sep 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective was to examine the effect of perindopril compared with placebo on the change in standing balance (postural stability) over a 15 week period in older people with falls.
Evidence from our group and others suggests that ACE inhibitors (ACEi) have a number of effects that might lead to a reduction in falls risk. These include beneficial effects on muscle function, nerve function, central postural integration and orthostatic hypotension (OH). However ACEi are often stopped in people with falls due to worries about increasing falls through worsening OH. We therefore aimed to study the effect of ACEi on postural stability as an intermediate phenotype for falls risk. Postural stability was measured using a force plate.
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Protection of trial subjects |
Potential participants were given the Participant Information sheet at least 24 hours prior to written informed consent being taken. The trial was explained to them and they were given opportunities to ask questions prior to consent. They were allowed withdraw from the study at any time.
At every visit participants were asked about potential adverse events and any adverse events were documented. This information was provided to the DMC for safety assessment.
Blood tests and blood pressure was measured at baseline, week 2, 5 and 15 to monitor renal function and blood pressure both of which can be affected by the trial medication. Protocol specified rules of uptitration or down titration of medication and when medication was to be discontinued. Clinical acumen was also employed to ensure participant safety.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Aug 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 80
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Worldwide total number of subjects |
80
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EEA total number of subjects |
80
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
64
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85 years and over |
16
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Recruitment
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Recruitment details |
From September 2013, 80 participants were recruited from Tayside and Fife. Last participant last visit was 30 September 2015. Participants aged > 65 years with ≥1 self-reported falls in the previous 12 months fulfilling inclusion and exclusion criteria were recruited. Sources were from primary care, secondary care and volunteers from community. | |||||||||||||||
Pre-assignment
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Screening details |
4289 potential participants were invited to participate . 3793 declined or did not reply, 408 were found ineligible on telephonic pre-screening and 88 attended a screening visit. 80 participants were randomised to receive perindopril or placebo. All usual medication was continued. | |||||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Assessor | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Perindopril | |||||||||||||||
Arm description |
Participants were randomised to receive Perindopril or placebo in a 1:1 ratio. Starting dose of 2 mg Perindopril was uptitrated to 4 mg after 2 weeks if tolerated. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Perindopril
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, soft
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Routes of administration |
Oral use
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Dosage and administration details |
Initial dose on randomisation was 2 mg which was uptitrated at 2 weeks to 4 mg if tolerated (Blood pressure and renal function).
If 2 mg was tolerated but not 4 mg, participant was kept on 2 mg for the duration of the study.
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Arm title
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Placebo | |||||||||||||||
Arm description |
Participants were randomised to receive Perindopril or placebo in a 1:1 ratio. The placebo group also received a mock uptitration at 2 weeks. | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
Perindopril
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, soft
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Routes of administration |
Oral use
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Dosage and administration details |
Initial dose on randomisation was 2 mg which was uptitrated at 2 weeks to 4 mg if tolerated (Blood pressure and renal function).
If 2 mg was tolerated but not 4 mg, participant was kept on 2 mg for the duration of the study.
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Baseline characteristics reporting groups
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Reporting group title |
Perindopril
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Reporting group description |
Participants were randomised to receive Perindopril or placebo in a 1:1 ratio. Starting dose of 2 mg Perindopril was uptitrated to 4 mg after 2 weeks if tolerated. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants were randomised to receive Perindopril or placebo in a 1:1 ratio. The placebo group also received a mock uptitration at 2 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Perindopril
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Reporting group description |
Participants were randomised to receive Perindopril or placebo in a 1:1 ratio. Starting dose of 2 mg Perindopril was uptitrated to 4 mg after 2 weeks if tolerated. | ||
Reporting group title |
Placebo
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Reporting group description |
Participants were randomised to receive Perindopril or placebo in a 1:1 ratio. The placebo group also received a mock uptitration at 2 weeks. |
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End point title |
Between group change in Anterioposterior sway (eyes closed) from baseline to 15 weeks | ||||||||||||||||||
End point description |
Primary outcome was Difference in static Anteroposterior (AP) sway at 15 weeks between the two groups, adjusted for baseline values.
Postural stability was measured using the Advanced Medical Technology Inc. force plate (measuring ground reaction force velocity and pressure distribution). For the static postural stability, participants stood on the force plate with feet slightly apart, eyes open and closed each for 40 seconds and this was repeated 3 times. The sway range was calculated.
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End point type |
Primary
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End point timeframe |
Assessed at baseline and at 15 weeks
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Statistical analysis title |
Between group difference in AP sway | ||||||||||||||||||
Statistical analysis description |
Analyses were performed comparing change in outcomes at 15 weeks using ANOVA, adjusted for baseline values of the variable under test. A multivariate model including treatment and any significant co-variables from baseline data gave similar results.
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Comparison groups |
Perindopril v Placebo
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Number of subjects included in analysis |
80
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.59 | ||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||
Point estimate |
2
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-7 | ||||||||||||||||||
upper limit |
12 |
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End point title |
Between group difference in Anterioposterior sway (eyes open) from baseline to 15 weeks | ||||||||||||||||||
End point description |
Difference in static Anteroposterior (AP) sway at 15 weeks between the two groups, adjusted for baseline values.
Postural stability was measured using the Advanced Medical Technology Inc. force plate (measuring ground reaction force velocity and pressure distribution). For the static postural stability, participants stood on the force plate with feet slightly apart, eyes open and closed each for 40 seconds and this was repeated 3 times.
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End point type |
Primary
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End point timeframe |
Outcome was measured at baseline and at 15 weeks
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Statistical analysis title |
Between group difference in AP sway | ||||||||||||||||||
Comparison groups |
Perindopril v Placebo
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Number of subjects included in analysis |
80
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.91 | ||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||
Point estimate |
0
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-8 | ||||||||||||||||||
upper limit |
7 |
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End point title |
Between group difference in mediolateral sway (eyes closed) from baseline to 15 weeks | ||||||||||||||||||
End point description |
Postural stability was measured using the Advanced Medical Technology Inc. force plate (measuring ground reaction force velocity and pressure distribution). For the static postural stability, participants stood on the force plate with feet slightly apart, eyes open and closed each for 40 seconds and this was repeated 3 times. Sway range in the mediolateral direction was calculated
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End point type |
Secondary
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End point timeframe |
Outcomes were measured at baseline and 15 weeks
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Statistical analysis title |
Change in mediolateral sway | ||||||||||||||||||
Statistical analysis description |
Analyses were performed comparing change in outcomes using ANOVA, adjusted for baseline values of the variable under test. The multivariate model including treatment and any significant co-variables gave similar results. Other types of analyses yielded similar results.
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Comparison groups |
Perindopril v Placebo
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Number of subjects included in analysis |
80
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.32 | ||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||
Point estimate |
-5
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-14 | ||||||||||||||||||
upper limit |
5 |
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End point title |
Between group difference in mediolateral sway (eyes open) from baseline to 15 weeks | ||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Outcome was measured at baseline and 15 weeks
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Statistical analysis title |
Between group difference in mediolateral sway | ||||||||||||||||||
Comparison groups |
Perindopril v Placebo
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Number of subjects included in analysis |
80
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.38 | ||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||
Point estimate |
-4
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-13 | ||||||||||||||||||
upper limit |
5 |
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End point title |
Between group difference in sway velocity (eyes closed) from baseline to 15 weeks | ||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Outcome measured at baseline and 15 weeks
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Statistical analysis title |
Between group differrence in sway velocity | ||||||||||||||||||
Comparison groups |
Perindopril v Placebo
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Number of subjects included in analysis |
80
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.41 | ||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||
Point estimate |
-3
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Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-8 | ||||||||||||||||||
upper limit |
3 |
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End point title |
Between group difference in sway velocity (eyes open) from baseline to 15 weeks | ||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Outcome measured at baseline and 15 weeks
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Statistical analysis title |
between group difference in sway velocity | ||||||||||||||||||
Comparison groups |
Perindopril v Placebo
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Number of subjects included in analysis |
80
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.42 | ||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||
Point estimate |
2
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Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-3 | ||||||||||||||||||
upper limit |
6 |
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End point title |
between group difference in total sway area (eyes closed) baseline to 15 weeks | ||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Outcome measured at baseline and 15 weeks
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Statistical analysis title |
Between group difference in total sway area | ||||||||||||||||||
Statistical analysis description |
Adjusted for baseline total sway area
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Comparison groups |
Perindopril v Placebo
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Number of subjects included in analysis |
80
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.62 | ||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||
Point estimate |
-150
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Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-757 | ||||||||||||||||||
upper limit |
457 |
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End point title |
Between group difference in total sway area ( eyes open) from baseline to 15 weeks | ||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Outcome measured at baseline and 15 weeks
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Statistical analysis title |
Between group difference in total sway area | ||||||||||||||||||
Comparison groups |
Perindopril v Placebo
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Number of subjects included in analysis |
80
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | ||||||||||||||||||
P-value |
= 0.43 | ||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||
Point estimate |
-179
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Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-634 | ||||||||||||||||||
upper limit |
275 | ||||||||||||||||||
Notes [1] - Adjusted for baseline variable |
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End point title |
Between group difference in anterioposterior reach | ||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Outcome measured at baseline and 15 weeks
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Statistical analysis title |
Between group difference in forward reach | ||||||||||||||||||
Statistical analysis description |
Adjusted for baseline variable
|
||||||||||||||||||
Comparison groups |
Perindopril v Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.62 | ||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||
Point estimate |
3
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-9 | ||||||||||||||||||
upper limit |
16 |
|
|||||||||||||||||||
End point title |
Between group difference in mediolateral left reach from baseline to 15 weeks | ||||||||||||||||||
End point description |
|||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
outcome measured at baseline and 15 weeks
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
Between group difference in left reach | ||||||||||||||||||
Statistical analysis description |
Adjusted for baseline variable
|
||||||||||||||||||
Comparison groups |
Perindopril v Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.08 | ||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||
Point estimate |
9
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-1 | ||||||||||||||||||
upper limit |
20 |
|
|||||||||||||||||||
End point title |
Between group difference in mediolateral right reach from baseline to 15 weeks | ||||||||||||||||||
End point description |
|||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Outcome measure at baseline and 15 weeks
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
Between group difference in right reach | ||||||||||||||||||
Statistical analysis description |
Adjusted for baseline variable
|
||||||||||||||||||
Comparison groups |
Perindopril v Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.45 | ||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||
Point estimate |
5
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-8 | ||||||||||||||||||
upper limit |
18 |
|
|||||||||||||||||||||||||
End point title |
Falls at baseline | ||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Reported at baseline - number of falls in 12 months prior to recruitment
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Falls during the study | ||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Number of falls reported in study period
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Between group difference in falls during the study | ||||||||||||||||||||||||
Statistical analysis description |
Number of falls data was skewed so a number of sensitivity analyses were done using different modelling techniques.
|
||||||||||||||||||||||||
Comparison groups |
Perindopril v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority [2] | ||||||||||||||||||||||||
P-value |
= 0.24 | ||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||
Point estimate |
1.7
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-1.1 | ||||||||||||||||||||||||
upper limit |
4.5 | ||||||||||||||||||||||||
Notes [2] - A number of sensitivity analyses using different modelling techniques were conducted to investigate the difference in falls between the two groups: Mixed model analysis mean difference 1.7 (-1.1 to 4.5, p=0.24); quasi-poisson regression mean difference -0.6 (-1.6 to 0.3, p=0.19); ordinal regression 0.4 (95% CI -0.9 to 1.6; p=0.58). Mixed model analyses are presented in the tables |
|
|||||||||||||||||||
End point title |
Between group difference in voluntary muscle strength (QMVC) | ||||||||||||||||||
End point description |
Isometric quadriceps maximum voluntary contraction strength (QMVC) was measured 3 times in a sitting position with the knee joint at 90 degrees using a Biopac tension dynamometer and output was recorded using a data acquisition system. QMVC was taken as the highest mean force that could be sustained over 1 second.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Outcome measure at baseline and 15 weeks
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
Between group difference in QMVC | ||||||||||||||||||
Comparison groups |
Perindopril v Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority [3] | ||||||||||||||||||
P-value |
= 0.11 | ||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||
Point estimate |
-1.4
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-3 | ||||||||||||||||||
upper limit |
0.3 | ||||||||||||||||||
Notes [3] - Adjusted for baseline variable |
|
|||||||||||||||||||||||||||||||
End point title |
Between group difference in Magnetic twitch of quadriceps (TwQ) | ||||||||||||||||||||||||||||||
End point description |
This was used to test non volitional muscle strength and fatigability in participants who had no contraindications to magnetic nerve stimulation. Greatest Twitch tension generated in the Quadriceps (TwQ) using magnetic femoral nerve stimulation with the Magstim 2002 device was recorded. Endurance was tested by repeated QMVC, until force fell to < 70% of baseline maximum QMVC and the number of ‘kicks’ were recorded. Magnetic stimulation was repeated to estimate fatigue immediately and 10 minutes later. Fatigability was further tested by measuring TwQ following a 6 minute walking test (6MW), a valid, reliable test of submaximal endurance capacity in older people.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Outcome measured at baseline and 15 weeks
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Statistical analysis title |
Between group difference in TwQ at rest | ||||||||||||||||||||||||||||||
Comparison groups |
Perindopril v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [4] | ||||||||||||||||||||||||||||||
P-value |
= 0.04 | ||||||||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
0.5
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
0 | ||||||||||||||||||||||||||||||
upper limit |
1 | ||||||||||||||||||||||||||||||
Notes [4] - Adjusting for baseline variable |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Between group difference in TwQ following kicks | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted for baseline variable
|
||||||||||||||||||||||||||||||
Comparison groups |
Perindopril v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||||
P-value |
= 0.08 | ||||||||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
0.8
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
-0.1 | ||||||||||||||||||||||||||||||
upper limit |
1.8 | ||||||||||||||||||||||||||||||
Statistical analysis title |
Between group difference in TwQ following 6MW | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted for baseline variable
|
||||||||||||||||||||||||||||||
Comparison groups |
Perindopril v Placebo
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||||
P-value |
= 0.35 | ||||||||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
0.2
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
-0.3 | ||||||||||||||||||||||||||||||
upper limit |
0.7 |
|
|||||||||||||||||||
End point title |
Between group difference in 6minute walking distance | ||||||||||||||||||
End point description |
|||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Outcome measured at baseline and 15 weeks
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
Between group difference in 6MW distance | ||||||||||||||||||
Statistical analysis description |
Adjusted for baseline variable
|
||||||||||||||||||
Comparison groups |
Perindopril v Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
equivalence | ||||||||||||||||||
P-value |
= 0.41 | ||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||
Point estimate |
-9
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-29 | ||||||||||||||||||
upper limit |
12 |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
During the study
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
At each visit participants were asked about any adverse events and these were recorded in the Adverse event log
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Perindopril
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Active arm receiving perindopril - adverse events occurring during the study | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Placebo arm - adverse events occurring during the study | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
21 Oct 2013 |
Change to the protocol to add an extra inclusion criteria, namely to add that participants must have been assessed at a Medicine for the Elderly (MFE) clinic within the past 18 months. This is to ensure that all participants have received standard treatment currently recommended for their falls risk. This will ensure that they are not recruited under the misperception that participating in this study is a substitute for standard care. |
||
26 Mar 2014 |
Amendment included several points:
1.A brief participant information sheet (BPIS) created
2.New Patient Information Sheet to replace the original Patient Information Sheet with a table of visits and tests added for ease of reference.
3. Heading on the poster, and PIS’s altered to ‘Falls Research Study’.
4.To send only the new brief PIS to potential participants initially. When these potential participants have contacted the study team to discuss the study further they will be sent a full Patient Information Sheet in advance of their screening visit to give them further details on the trial.
5. To distribute posters and brief PISs to community settings .
6. Additional information in Participant Information Sheet regarding contact details for participants if they become unwell during the study and advice on what to do if feeling unwell on study medications.
7. Following a redesign in services, people who fall were referred from different sources to a Falls Coordinator We therefore extended recruitment through this Falls service.
8. Use of 24 hour BP monitor in participants with high screening BP in case there was a white coat effect
9. Measure postural BP at home visits as per DMC suggestion
10. Extend recruitment to NHS Fife in addition to NHS Tayside
|
||
26 Nov 2014 |
Protocol: We have added that we wish to use the national SHARE registry as a potential source of recruitment - this database has Tayside and Fife volunteers who have given prior consent to be approached for clinical research projects which could be a useful source of recruitment.
To the PIS: We added the new number for NHS 24 and put the NHS Tayside logo on the PIS. We have had a recent Data Monitoring Committee and they specifically requested that we give consideration to spelling out clearly in the PIS that if a participant experiences diarrhoea or vomiting they are to stop study meds immediately.
Addition of new invitation letter to patients who have been seen on the wards as part of the Medicine for the Elderly (MFE) services.
|
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
Please note that issues with AE resolution reporting were identified by an MHRA inspection in July 2016, data were reanalyzed after correction of errors - hence date of final analysis is 26/10/16 and report posting is beyond a year from end of trial |