Clinical Trial Results:
A randomised placebo-controlled trial of fixed-dose combination medication in those at raised risk of cardiovascular disease
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Summary
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EudraCT number |
2007-002466-35 |
Trial protocol |
NL GB |
Global end of trial date |
22 Dec 2009
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Results information
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Results version number |
v1(current) |
This version publication date |
16 May 2020
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First version publication date |
16 May 2020
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Other versions |
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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 |
Polypill
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Other trial identifiers |
Australian New Zealand Clinical Trials Registry: ACTRN12607000099426 | ||
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Sponsors
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Sponsor organisation name |
Imperial College London
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Sponsor organisation address |
South Kensington Campus, London, United Kingdom, SW7 2AZ
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Public contact |
PROFESSOR SIMON THOM, Imperial College London, +44 (0)20 7594 1100, s.thom@imperial.ac.uk
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Scientific contact |
PROFESSOR SIMON THOM, Imperial College London, +44 (0)20 7594 1100, s.thom@imperial.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 Dec 2010
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
22 Dec 2009
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Dec 2009
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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 aim of the trial is to evaluate whether a “polypill” a fixed low dose combination of blood pressure lowering drugs (an ACE inhibitor and diurectic), cholesterol lowering drugs (a statin) and asprin results in improved systolic Blood Pressue and LDL-cholesterol(bad cholesterol) levels and is tolerable compared with placebo (a tablet containing no medication) in individuals at raised risk of 7.5% or more in the next 5 years of a major cardiovascular event, such as a heart attack or stroke. (This estimate is made by considering a number of factors including your age, gender, blood pressure, cholesterol level and whether you smoke).
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Protection of trial subjects |
None
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
17 Oct 2007
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Netherlands: 102
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Country: Number of subjects enrolled |
United Kingdom: 113
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Country: Number of subjects enrolled |
Australia: 21
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Country: Number of subjects enrolled |
Brazil: 8
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Country: Number of subjects enrolled |
India: 109
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Country: Number of subjects enrolled |
New Zealand: 12
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Country: Number of subjects enrolled |
United States: 13
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Worldwide total number of subjects |
378
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EEA total number of subjects |
215
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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) |
261
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From 65 to 84 years |
117
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were recruited from 17 October 2008 to 22 December 2009. | |||||||||||||||
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Pre-assignment
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Screening details |
After screening, 481 participants were ineligible (due to too low Cv risk, did not complete the form, too high CV risk) and 378 eligible. | |||||||||||||||
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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 | |||||||||||||||
Blinding implementation details |
Participants, research staff and and co-ordinating centre staff were all blinded to the allocation
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Red Heart Pill | |||||||||||||||
Arm description |
Participants received Red Heart Pill (RHP, a polypill comprising a bilayered tablet containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg, and simvastatin 20 mg) for 12 weeks | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Red Heart Pill
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
The polypill comprising a bilayered tablet containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg, and simvastatin 20 mg)
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Arm title
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Placebo | |||||||||||||||
Arm description |
Participants received placebo | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Tablet for 12 weeks
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Baseline characteristics reporting groups
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Reporting group title |
Red Heart Pill
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Reporting group description |
Participants received Red Heart Pill (RHP, a polypill comprising a bilayered tablet containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg, and simvastatin 20 mg) for 12 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants received placebo | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Red Heart Pill
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Reporting group description |
Participants received Red Heart Pill (RHP, a polypill comprising a bilayered tablet containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg, and simvastatin 20 mg) for 12 weeks | ||
Reporting group title |
Placebo
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Reporting group description |
Participants received placebo | ||
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End point title |
Changes in Systolic blood pressure [1] [2] | ||||||||
End point description |
Intention-to-treat analyses.
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End point type |
Primary
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End point timeframe |
12 weeks
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| 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 analysis was by intention-to-treat. Means of changes in systolic blood pressure values from baseline to 12 weeks between polypill and placebo groups were compared using a 2 sample t-test. Adjusted analyses were carried out by including the stratification factors in an analysis of the covariance regression model with a change in the blood pressure variable as the dependent variable by SAS. The result is p<0.0001. [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The primary analysis was by intention-to-treat. Means of changes in systolic blood pressure values from baseline to 12 weeks between polypill and placebo groups were compared using a 2 sample t-test. Adjusted analyses were carried out by including the stratification factors in an analysis of the covariance regression model with a change in the blood pressure variable as the dependent variable by SAS. The result is p<0.0001. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Changes in LDL-cholesterol [3] [4] | ||||||||
End point description |
Intention-to-treat analyses.
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End point type |
Primary
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End point timeframe |
12 weeks
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| Notes [3] - 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 analysis was by intention-to-treat. Means of changes in LDL-cholesterol values from baseline to 12 weeks between polypill and placebo groups were compared using a 2 sample t-test. Adjusted analyses were carried out by including the stratification factors in an analysis of the covariance regression model with a change in the lipid variable as the dependent variable by SAS. The result is p<0.0001. [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The primary analysis was by intention-to-treat. Means of changes in LDL-cholesterol values from baseline to 12 weeks between polypill and placebo groups were compared using a 2 sample t-test. Adjusted analyses were carried out by including the stratification factors in an analysis of the covariance regression model with a change in the lipid variable as the dependent variable by SAS. The result is p<0.0001. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Changes in Diastolic blood pressure [5] | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
12 weeks
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| Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The primary analysis was by intention-to-treat. Means of changes in diastolic blood pressure values from baseline to 12 weeks between polypill and placebo groups were compared using a 2 sample t-test. Adjusted analyses were carried out by including the stratification factors in an analysis of the covariance regression model with a change in the blood pressure variable as the dependent variable by SAS. The result is p<0.0001. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Changes in Total cholesterol [6] | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
12 weeks
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| Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The primary analysis was by intention-to-treat. Means of changes in total cholesterol values from baseline to 12 weeks between polypill and placebo groups were compared using a 2 sample t-test. Adjusted analyses were carried out by including the stratification factors in an analysis of the covariance regression model with a change in the lipid variable as the dependent variable by SAS. The result is p<0.0001. |
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Adverse events information
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Timeframe for reporting adverse events |
12 weeks
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
10
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Reporting groups
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Reporting group title |
Red Heart Pill
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Reporting group description |
Participants received Red Heart Pill (RHP, a polypill comprising a bilayered tablet containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg, and simvastatin 20 mg) for 12 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants received placebo | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/21647425 |
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