Ignite Creation Date:
2024-05-05 @ 4:37 PM
Last Modification Date:
2024-10-26 @ 9:22 AM
Study NCT ID:
NCT00274612
Status:
COMPLETED
Last Update Posted:
2013-11-01
First Post:
2006-01-10
Brief Title:
Prospective Randomised Investigation of the Safety and Efficacy of Micardis vs Ramipril Using ABPM
Sponsor:
Boehringer Ingelheim
Organization:
Boehringer Ingelheim
Study Overview
Official Title:
A Prospective Randomised Open- Label Blinded-Endpoint PROBE Trial Comparing Telmisartan MICARDIS 40-80-80mg QD and Ramipril 25-5--10mg QD in Patients With Mild-to-Moderate Hypertension Using Ambulatory Blood Pressure Monitoring PRISMA Prospective Randomised Investigation of the Safety and Efficacy of Micardis vs Ramipril Using ABPM
Status:
COMPLETED
Status Verified Date:
2013-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PRISMA
Brief Summary:
The primary objective of this study is to demonstrate that telmisartan 80 mg MICARDIS is at least as effective and possibly superior to ramipril 5mg and 10mg in lowering mean ambulatory diastolic blood pressure DBP and systolic blood pressure SBP during the last 6 hours of the 24-hour dosing interval in mild-to-moderate hypertensive patients at the end of an 8 and 14-week treatment period respectively
Detailed Description:
Secondary objectives will compare telmisartan 80 mg MICARDIS and ramipril 5 mg and 10 mg on 1 the reduction in the last 6-hour ABPM mean pulse pressure PP relative to dosing 2 the reductions in the 24-hour ABPM mean DBP SBP and PP relative to dosing 3 reductions in ABPM mean DBP SBP and PP during other periods of the 24-hour dosing interval ie morning daytime and nighttime relative to clock time 4 change from baseline in systolic and diastolic blood pressure load during the 24-hour dosing interval 5 reductions in the mean seated trough DBP and SBP measured using a manual in-clinic cuff sphygmomanometer 6 responder rates as determined by both ABPM and manual in-clinic cuff measurements and 7 Health-Related Quality of Life HRQL
Study Hypothesis
It is hypothesised that the rise of blood pressure BP during the last hours of the sleeping period is a cause of the high incidence of cardiovascular events in the morning The purpose of the present study is to demonstrate that telmisartan MICARDIS is not inferior to ramipril in lowering blood pressure in patients with mild-to-moderate hypertension Blood pressure will be assessed by ambulatory blood pressure monitoring ABPM as this will allow comparison of the full 24-hour effects of both treatments without artefacts eg white-coat hypertension introduced by measurement of blood pressure in the clinic This will measure diastolic blood pressures over the entire 24-hour dosing interval with primary attention focused on the last six hours of the dosing interval
NULL AND ALTERNATIVE HYPOTHESES In order to test the multiple hypotheses eg non-inferiority and superiority of telmisartan compared to ramipril multiple dosages ie telmisartan 80mg MICARDIS versus ramipril 5mg and ramipril 10mg after 8 and 14 weeks of treatment respectively and the two endpoints ie reduction in DBP and SBP during the last 6 hours of the 24-hour dosing interval as measured by ABPM a completely hierarchical closed testing procedure will be used
Hierarchical Closed Testing Procedure
1 Non-inferiority of telmisartan 80 mg MICARDIS compared to ramipril 5 mg at the end of the 8 week treatment period in the reduction of DBP during the last 6 hours of the 24 hour dosing interval if significant then
2 Superiority of telmisartan 80 mg MICARDIS compared to ramipril 5 mg at the end of the 8-week treatment period in the reduction of DBP during the last 6 hours of the 24-hour dosing interval if significant then
3 Superiority of telmisartan 80mg MICARDIS compared to ramipril 5 mg at the end of the 8-week treatment period in the reduction of SBP during the last 6 hours of the 24-hour dosing interval if significant then
4 Non-inferiority of telmisartan 80mg MICARDIS compared to ramipril 10 mg at the end of an 14 week treatment period in the reduction of DBP during the last 6 hours of the 24-hour dosing interval if significant then
5 Superiority of telmisartan 80mg MICARDIS compared to ramipril 10 mg at the end of an 14-week treatment period in the reduction of DBP during the last 6 hours of the 24-hour dosing interval and if significant then
6 Superiority of telmisartan 80mg MICARDIS compared to ramipril 10mg at the end of an 14-week treatment period in the reduction of SBP during the last 6 hours of the 24-hour dosing interval
A difference of 2 mmHg was determined to be the maximum difference between the mean reductions in DBP during the last 6 hours of the 24-hour dosing interval for the two treatments which would be considered to have no clinical importance ie the limit for non inferiority Thus non-inferiority of telmisartan compared to ramipril will be tested using the following set of hypotheses
Null Hypothesis
The overall mean reduction from baseline in ABPM mean DBP during the last 6 hours of the 24-hour dosing interval for telmisartan 80 mg MICARDIS is inferior to that for ramipril by at least 2 mmHg
Alternative Hypothesis The overall mean reduction from baseline in ABPM mean DBP during the last 6 hours of the 24-hour dosing interval for telmisartan 80mg MICARDIS is less than 2 mmHg smaller than that for ramipril
These hypotheses can be stated as
H0 dT - dR less than or equal to -2 mmHg versus HA dT - dR -2 mmHg where dT and dR represent the overall mean reduction from baseline in ABPM mean DBP during the last 6 hours of the 24-hour dosing interval for telmisartan and ramipril respectively adjusted for any other factors included in the statistical model
If the lower limit of the two-sided 95 confidence interval for the difference between the least square means of both treatments telmisartan - ramipril lies above -2 mmHg then it will be concluded that telmisartan 80mg MICARDIS is at least as effective as ramipril 5mg after 8 weeks of treatment or 10mg after 14 weeks of treatment depending upon the comparison in reducing DBP during the last 6 hours of the 24-hour dosing interval
Superiority of telmisartan MICARDIS compared to ramipril will be tested using the following set of hypotheses
Null Hypothesis
The overall mean reduction from baseline in the ABPM mean during the last 6 hours of the 24-hour dosing interval for telmisartan 80mg MICARDIS is less than or equal to that for ramipril
Alternative Hypothesis The overall mean reduction from baseline in the ABPM mean during the last 6 hours of the 24-hour dosing interval for telmisartan 80mg MICARDIS is greater than that for ramipril
These hypotheses can be stated as
H0 dT - dR less than or equal to 0 mmHg versus HA dT - dR 0 mmHg where dT and dR represent the overall mean reduction from baseline in ABPM mean DBP during the last 6 hours of the 24-hour dosing interval for telmisartan and ramipril respectively adjusted for any other factors included in the statistical model
If the lower limit of the two-sided 95 confidence interval for the difference between the least square means of both treatments telmisartan MICARDIS - ramipril is greater than zero then it will be concluded that telmisartan 80mg MICARDIS is statistically superior to ramipril 5mg after 8 weeks of treatment or 10mg after 14 weeks of treatment depending upon the comparison in reducing blood pressure DBP or SBP depending upon the comparison during the last 6 hours of the 24-hour dosing interval
Comparisons
Reductions in blood pressure during the last 6 hours of the 24-hour dosing interval as measured by ABPM in patients treated with telmisartan MICARDIS compared to patients treated with ramipril The primary analysis will consist of a closed testing procedure first testing for non-inferiority of telmisartan 80mg MICARDIS compared to ramipril 10mg after fourteen weeks of treatment in the reduction in diastolic blood pressure DBP if significant testing for superiority of telmisartan 80 mg MICARDIS compared to ramipril 10 mg in the reduction in DBP if significant testing for superiority of telmisartan 80 mg MICARDIS compared to ramipril 10 mg in the reduction of systolic blood pressure SBP if significant testing for non-inferiority of telmisartan 80 mg MICARDIS compared to ramipril 5 mg after eight weeks of treatment in the reduction in DBP if significant testing for superiority of telmisartan 80 mg MICARDIS compared to ramipril 5 mg in the reduction in DBP and if significant testing for superiority of telmisartan 80mg MICARDIS compared to ramipril 5mg in the reduction in SBP
Study Hypothesis
It is hypothesised that the rise of blood pressure BP during the last hours of the sleeping period is a cause of the high incidence of cardiovascular events in the morning The purpose of the present study is to demonstrate that telmisartan MICARDIS is not inferior to ramipril in lowering blood pressure in patients with mild-to-moderate hypertension Blood pressure will be assessed by ambulatory blood pressure monitoring ABPM as this will allow comparison of the full 24-hour effects of both treatments without artefacts eg white-coat hypertension introduced by measurement of blood pressure in the clinic This will measure diastolic blood pressures over the entire 24-hour dosing interval with primary attention focused on the last six hours of the dosing interval
NULL AND ALTERNATIVE HYPOTHESES In order to test the multiple hypotheses eg non-inferiority and superiority of telmisartan compared to ramipril multiple dosages ie telmisartan 80mg MICARDIS versus ramipril 5mg and ramipril 10mg after 8 and 14 weeks of treatment respectively and the two endpoints ie reduction in DBP and SBP during the last 6 hours of the 24-hour dosing interval as measured by ABPM a completely hierarchical closed testing procedure will be used
Hierarchical Closed Testing Procedure
1 Non-inferiority of telmisartan 80 mg MICARDIS compared to ramipril 5 mg at the end of the 8 week treatment period in the reduction of DBP during the last 6 hours of the 24 hour dosing interval if significant then
2 Superiority of telmisartan 80 mg MICARDIS compared to ramipril 5 mg at the end of the 8-week treatment period in the reduction of DBP during the last 6 hours of the 24-hour dosing interval if significant then
3 Superiority of telmisartan 80mg MICARDIS compared to ramipril 5 mg at the end of the 8-week treatment period in the reduction of SBP during the last 6 hours of the 24-hour dosing interval if significant then
4 Non-inferiority of telmisartan 80mg MICARDIS compared to ramipril 10 mg at the end of an 14 week treatment period in the reduction of DBP during the last 6 hours of the 24-hour dosing interval if significant then
5 Superiority of telmisartan 80mg MICARDIS compared to ramipril 10 mg at the end of an 14-week treatment period in the reduction of DBP during the last 6 hours of the 24-hour dosing interval and if significant then
6 Superiority of telmisartan 80mg MICARDIS compared to ramipril 10mg at the end of an 14-week treatment period in the reduction of SBP during the last 6 hours of the 24-hour dosing interval
A difference of 2 mmHg was determined to be the maximum difference between the mean reductions in DBP during the last 6 hours of the 24-hour dosing interval for the two treatments which would be considered to have no clinical importance ie the limit for non inferiority Thus non-inferiority of telmisartan compared to ramipril will be tested using the following set of hypotheses
Null Hypothesis
The overall mean reduction from baseline in ABPM mean DBP during the last 6 hours of the 24-hour dosing interval for telmisartan 80 mg MICARDIS is inferior to that for ramipril by at least 2 mmHg
Alternative Hypothesis The overall mean reduction from baseline in ABPM mean DBP during the last 6 hours of the 24-hour dosing interval for telmisartan 80mg MICARDIS is less than 2 mmHg smaller than that for ramipril
These hypotheses can be stated as
H0 dT - dR less than or equal to -2 mmHg versus HA dT - dR -2 mmHg where dT and dR represent the overall mean reduction from baseline in ABPM mean DBP during the last 6 hours of the 24-hour dosing interval for telmisartan and ramipril respectively adjusted for any other factors included in the statistical model
If the lower limit of the two-sided 95 confidence interval for the difference between the least square means of both treatments telmisartan - ramipril lies above -2 mmHg then it will be concluded that telmisartan 80mg MICARDIS is at least as effective as ramipril 5mg after 8 weeks of treatment or 10mg after 14 weeks of treatment depending upon the comparison in reducing DBP during the last 6 hours of the 24-hour dosing interval
Superiority of telmisartan MICARDIS compared to ramipril will be tested using the following set of hypotheses
Null Hypothesis
The overall mean reduction from baseline in the ABPM mean during the last 6 hours of the 24-hour dosing interval for telmisartan 80mg MICARDIS is less than or equal to that for ramipril
Alternative Hypothesis The overall mean reduction from baseline in the ABPM mean during the last 6 hours of the 24-hour dosing interval for telmisartan 80mg MICARDIS is greater than that for ramipril
These hypotheses can be stated as
H0 dT - dR less than or equal to 0 mmHg versus HA dT - dR 0 mmHg where dT and dR represent the overall mean reduction from baseline in ABPM mean DBP during the last 6 hours of the 24-hour dosing interval for telmisartan and ramipril respectively adjusted for any other factors included in the statistical model
If the lower limit of the two-sided 95 confidence interval for the difference between the least square means of both treatments telmisartan MICARDIS - ramipril is greater than zero then it will be concluded that telmisartan 80mg MICARDIS is statistically superior to ramipril 5mg after 8 weeks of treatment or 10mg after 14 weeks of treatment depending upon the comparison in reducing blood pressure DBP or SBP depending upon the comparison during the last 6 hours of the 24-hour dosing interval
Comparisons
Reductions in blood pressure during the last 6 hours of the 24-hour dosing interval as measured by ABPM in patients treated with telmisartan MICARDIS compared to patients treated with ramipril The primary analysis will consist of a closed testing procedure first testing for non-inferiority of telmisartan 80mg MICARDIS compared to ramipril 10mg after fourteen weeks of treatment in the reduction in diastolic blood pressure DBP if significant testing for superiority of telmisartan 80 mg MICARDIS compared to ramipril 10 mg in the reduction in DBP if significant testing for superiority of telmisartan 80 mg MICARDIS compared to ramipril 10 mg in the reduction of systolic blood pressure SBP if significant testing for non-inferiority of telmisartan 80 mg MICARDIS compared to ramipril 5 mg after eight weeks of treatment in the reduction in DBP if significant testing for superiority of telmisartan 80 mg MICARDIS compared to ramipril 5 mg in the reduction in DBP and if significant testing for superiority of telmisartan 80mg MICARDIS compared to ramipril 5mg in the reduction in SBP
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None