Clinical Trial Results:
ENOS: Efficacy of Nitric Oxide in Stroke. Estudio ENOS: Eficacia del óxido nítrico en el ictus
Summary
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EudraCT number |
2004-003870-27 |
Trial protocol |
ES DK SE GR |
Global end of trial date |
22 Oct 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Feb 2019
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First version publication date |
24 Feb 2019
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Other versions |
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Summary report(s) |
Effi cacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke (ENOS): a partial-factorial randomised controlled trial |
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 |
RA2363
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Additional study identifiers
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ISRCTN number |
ISRCTN99414122 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
University of Nottingham
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Sponsor organisation address |
R&I, East Atrium Jubilee Conference Centre, Nottingham, United Kingdom, NG8 1DH
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Public contact |
Philip Bath, University of Nottingham, +44 115 823 1765, philip.bath@nottingham.ac.uk
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Scientific contact |
Angela Shone, University of Nottingham, +44 115 84 67906, angela.shone@nottingham.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 |
22 Oct 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
22 Oct 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Oct 2014
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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 |
Efficacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke
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Protection of trial subjects |
N/A
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 Jul 2001
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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 |
Spain: 8
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Country: Number of subjects enrolled |
Sweden: 14
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Country: Number of subjects enrolled |
Denmark: 17
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Country: Number of subjects enrolled |
Greece: 12
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Country: Number of subjects enrolled |
Italy: 33
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Country: Number of subjects enrolled |
United Kingdom: 2545
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Country: Number of subjects enrolled |
Australia: 8
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Country: Number of subjects enrolled |
Canada: 33
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Country: Number of subjects enrolled |
China: 103
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Country: Number of subjects enrolled |
Egypt: 148
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Country: Number of subjects enrolled |
Ireland: 10
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Country: Number of subjects enrolled |
Georgia: 195
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Country: Number of subjects enrolled |
Hong Kong: 4
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Country: Number of subjects enrolled |
India: 157
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Country: Number of subjects enrolled |
Malaysia: 14
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Country: Number of subjects enrolled |
Norway: 4
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Country: Number of subjects enrolled |
New Zealand: 71
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Country: Number of subjects enrolled |
Philippines: 16
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Country: Number of subjects enrolled |
Poland: 123
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Country: Number of subjects enrolled |
Romania: 217
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Country: Number of subjects enrolled |
Singapore: 155
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Country: Number of subjects enrolled |
Sri Lanka: 110
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Country: Number of subjects enrolled |
Turkey: 14
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Worldwide total number of subjects |
4011
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EEA total number of subjects |
2983
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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) |
1244
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From 65 to 84 years |
2299
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85 years and over |
468
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Recruitment
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Recruitment details |
Between 20th July 2001 and 14th October 2013, 4011 patients from 173 sites were enrolled across 23 countries | |||||||||||||||||||||||||
Pre-assignment
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Screening details |
Inclusion criteria: Within 48 hours of stroke onset with raised systolic blood pressure of 140 - 220mmHg Patients who were taking antihypertensives were also randomised to either continue or stop their treatment | |||||||||||||||||||||||||
Period 1
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Period 1 title |
Randomisation
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind [1] | |||||||||||||||||||||||||
Roles blinded |
Subject, Monitor, Data analyst, Carer, Assessor | |||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
No
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Arm title
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GTN arm | |||||||||||||||||||||||||
Arm description |
Treatment arm | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Glyceryl trinitrate
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Impregnated pad
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Routes of administration |
Transdermal use
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Dosage and administration details |
5mg patch applied once per day for 7 days
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Arm title
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No GTN | |||||||||||||||||||||||||
Arm description |
No active treatment patch given | |||||||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Continue antihypertensives | |||||||||||||||||||||||||
Arm description |
Continuing prior antihypertensive treatment | |||||||||||||||||||||||||
Arm type |
Continuing antihypertensives | |||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Stop antihypertensives | |||||||||||||||||||||||||
Arm description |
Stop prior antihypertensive treatment | |||||||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Notes [1] - The number of roles blinded appears inconsistent with a single blinded trial. It is expected that there will be one role blinded in a single blind trial. Justification: Participant was blinded |
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Period 2
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Period 2 title |
Day 90
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Is this the baseline period? |
No | |||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind [2] | |||||||||||||||||||||||||
Roles blinded |
Subject, Monitor, Data analyst, Carer, Assessor | |||||||||||||||||||||||||
Blinding implementation details |
Day 90 follow up coordinator blinded to treatment assignments
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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GTN arm | |||||||||||||||||||||||||
Arm description |
Treatment arm | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Glyceryl trinitrate
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Impregnated pad
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Routes of administration |
Transdermal use
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Dosage and administration details |
5mg patch applied once per day for 7 days
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Arm title
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No GTN | |||||||||||||||||||||||||
Arm description |
No active treatment patch given | |||||||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Continue antihypertensives | |||||||||||||||||||||||||
Arm description |
Continuing prior antihypertensive treatment | |||||||||||||||||||||||||
Arm type |
Continue antihypertensives | |||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Stop antihypertensives | |||||||||||||||||||||||||
Arm description |
Stop prior antihypertensive treatment | |||||||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Notes [2] - The number of roles blinded appears inconsistent with a single blinded trial. It is expected that there will be one role blinded in a single blind trial. Justification: Participant was blinded |
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Baseline characteristics reporting groups
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Reporting group title |
GTN arm
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Reporting group description |
Treatment arm | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
No GTN
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Reporting group description |
No active treatment patch given | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Continue antihypertensives
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Reporting group description |
Continuing prior antihypertensive treatment | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Stop antihypertensives
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Reporting group description |
Stop prior antihypertensive treatment | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
GTN arm
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Reporting group description |
Treatment arm | ||
Reporting group title |
No GTN
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Reporting group description |
No active treatment patch given | ||
Reporting group title |
Continue antihypertensives
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Reporting group description |
Continuing prior antihypertensive treatment | ||
Reporting group title |
Stop antihypertensives
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Reporting group description |
Stop prior antihypertensive treatment | ||
Reporting group title |
GTN arm
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Reporting group description |
Treatment arm | ||
Reporting group title |
No GTN
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Reporting group description |
No active treatment patch given | ||
Reporting group title |
Continue antihypertensives
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Reporting group description |
Continuing prior antihypertensive treatment | ||
Reporting group title |
Stop antihypertensives
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Reporting group description |
Stop prior antihypertensive treatment |
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End point title |
Day 90 mRs | ||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day 90
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Statistical analysis title |
Primary outcome analysis GTN | ||||||||||||||||||||
Comparison groups |
GTN arm v No GTN
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Number of subjects included in analysis |
3995
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.83 | ||||||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||||||
Point estimate |
1.01
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Confidence interval |
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level |
95% | ||||||||||||||||||||
sides |
2-sided
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lower limit |
0.91 | ||||||||||||||||||||
upper limit |
1.13 | ||||||||||||||||||||
Statistical analysis title |
Primary analysis - continue/stop | ||||||||||||||||||||
Comparison groups |
Continue antihypertensives v Stop antihypertensives
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Number of subjects included in analysis |
2090
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.55 | ||||||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||||||
Point estimate |
1.05
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Confidence interval |
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level |
95% | ||||||||||||||||||||
sides |
2-sided
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lower limit |
0.9 | ||||||||||||||||||||
upper limit |
1.22 |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Up to day 90
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Assessment type |
Systematic | ||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||
Dictionary version |
16
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Reporting groups
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Reporting group title |
All participants
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Reporting group description |
- | ||||||||||||||||||||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: ENOS had a pre-specified list of adverse events for reporting |
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
N/A | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/25465108 |