Ignite Creation Date:
2024-05-05 @ 12:03 PM
Last Modification Date:
2024-10-26 @ 9:20 AM
Study NCT ID:
NCT00239538
Status:
COMPLETED
Last Update Posted:
2013-11-08
First Post:
2005-10-14
Brief Title:
SMOOTH - Blood Pressure Control in DiabeticObese Patients
Sponsor:
Boehringer Ingelheim
Organization:
Boehringer Ingelheim
Study Overview
Official Title:
Prospective Randomized Open-label Blinded Endpoint Forced Titration Study to Compare Telmisartan Combined With HCTZ 80mg125mg to Valsartan Combined With HCTZ 160mg125mg for the Control of Mild-to-moderate Hypertension in Obese Patients With Type 2 Diabetes Mellitus Using ABPM
Status:
COMPLETED
Status Verified Date:
2013-11
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:
None
Brief Summary:
The primary objective of this study is to demonstrate that telmisartan 80 mg combined with hydrochlorothiazide 125 mg T80H125 is at least as effective and possibly superior to valsartan 160 mg combined with hydrochlorothiazide 125 mg V160H125 in lowering mean ambulatory systolic blood pressure SBP and diastolic blood pressure DBP during the last 6 hours of the 24-hour dosing interval at the end of a 10-week treatment period in mild-to-moderate hypertensive overweight or obese patients with type 2 diabetes mellitus
Detailed Description:
Methodology
Prospective randomised open-label blinded end-point forced-titration parallel group comparison using Ambulatory Blood Pressure Monitoring ABPM
PlannedActual Number of Subjects
Enrolled 15002085 Randomised 750840 Complete 680752
Diagnosis and Main Criteria for Inclusion
1 Mild-to-moderate hypertension defined as a baseline mean seated cuff DBP of 95 - 109 inclusive mmHg andor SBP of 140-179 inclusive mmHg and a baseline 24-hour ABPM mean DBP 85 mmHg andor SBP 130 mmHg 2 Overweight or obese as defined by a Body Mass Index BMI 27 kgm2 in non-Asians and 24 kgm2 in Asians 3 Type-2 diabetes mellitus 4 At least 30 years of age
Duration of Treatment
10 weeks total telmisartan 80 mg or valsartan 160 mg for 4 weeks followed by telmisartan 80 mg plus hydrochlorothiazide 125 mg or valsartan 160 mg plus hydrochlorothiazide 125 mg for an additional 6 weeks
Criteria for Efficacy
Primary Endpoint
Reductions in blood pressure during the last 6 hours of the 24-hour dosing interval as measured by ABPM The primary analysis will consist of comparing telmisartan combined with hydrochlorothiazide 80 mg125 mg to valsartan combined with hydrochlorothiazide 160 mg125 mg at the end of the 10-week study using a closed testing procedure first testing for non-inferiority based on SBP if significant testing for non-inferiority based on DBP if significant testing for superiority based on SBP and if significant testing for superiority based on DBP
Secondary Endpoints
Statistically greater reductions in ambulatory blood pressure for patients treated with telmisartan combined with hydrochlorothiazide 80 mg125 mg compared to patients treated with valsartan combined with hydrochlorothiazide 160 mg125 mg at the end of the 10-week study as measured by 1 Changes from baseline in the last 6 hours of the 24-hour dosing interval for pulse pressure 2 Changes from baseline in the 24-hour ABPM mean relative to dose time for SBP DBP and pulse pressure 3 Changes from baseline in the ABPM mean SBP DBP and pulse pressure relative to clock time during other periods ie morning daytime night time of the 24-hour dosing interval 4 Change from baseline in systolic and diastolic blood pressure load during the 24-hour dosing interval and 5 Percentage of patients responding to treatment based on the 24-hour ABPM mean SBP and DBP relative to dose time
Statistically greater reduction in mean seated trough blood pressure patients treated with telmisartan combined with hydrochlorothiazide 80 mg125 mg compared to patients treated with valsartan combined with hydrochlorothiazide 160 mg125 mg at the end of the 10-week study as measured by 1 Changes from baseline in mean seated trough SBP and DBP as determined by electronic or manual device in-clinic and 2 Percentage of patients responding to treatment based on electronic or manual in-clinic trough cuff blood pressures
Evaluation of other endpoints comparing telmisartan combined with hydrochlorothiazide 80 mg125 mg to valsartan combined with hydrochlorothiazide 160 mg125 mg respectively including 1 Changes from baseline in metabolic markers serum TG LDL-C HDL-C total cholesterol potassium fasting glucose and HbA1C and for urine Na K Cl proteinuria as measured by spot urine for proteincreatinine ratio and 2 inflammatory markers serum high sensitive C-reactive protein serum homocysteine and plasma fibrinogen
Criteria for Safety
Evaluation of adverse events physical examinations laboratory assessments pulse rate and cuff blood pressure monitoring
Statistical Method
Analysis of covariance with treatment and centre as main effects and baseline as a covariate Mantel-Haenszel test controlling for centre
Study Hypothesis
Null Hypothesis
The overall mean change from baseline in the automated blood pressure monitor mean blood pressure during the last 6 hours of the 24-hour dosing interval for telmisartan 80 mg plus hydrochlorothiazide 125 mg is less than or equal to that for valsartan 160 mg plus hydrochlorothiazide 125 mg
Alternative Hypothesis
The overall mean change from baseline in the automated blood pressure monitor mean blood pressure during the last 6 hours of the 24-hour dosing interval for telmisartan 80 mg plus hydrochlorothiazide 125 mg is greater than that for valsartan 160 mg plus hydrochlorothiazide 125 mg
Comparisons
Telmisartan 80 mg plus hydrochlorothiazide 125 mg vs valsartan 160 mg plus hydrochlorothiazide 125 mg
Prospective randomised open-label blinded end-point forced-titration parallel group comparison using Ambulatory Blood Pressure Monitoring ABPM
PlannedActual Number of Subjects
Enrolled 15002085 Randomised 750840 Complete 680752
Diagnosis and Main Criteria for Inclusion
1 Mild-to-moderate hypertension defined as a baseline mean seated cuff DBP of 95 - 109 inclusive mmHg andor SBP of 140-179 inclusive mmHg and a baseline 24-hour ABPM mean DBP 85 mmHg andor SBP 130 mmHg 2 Overweight or obese as defined by a Body Mass Index BMI 27 kgm2 in non-Asians and 24 kgm2 in Asians 3 Type-2 diabetes mellitus 4 At least 30 years of age
Duration of Treatment
10 weeks total telmisartan 80 mg or valsartan 160 mg for 4 weeks followed by telmisartan 80 mg plus hydrochlorothiazide 125 mg or valsartan 160 mg plus hydrochlorothiazide 125 mg for an additional 6 weeks
Criteria for Efficacy
Primary Endpoint
Reductions in blood pressure during the last 6 hours of the 24-hour dosing interval as measured by ABPM The primary analysis will consist of comparing telmisartan combined with hydrochlorothiazide 80 mg125 mg to valsartan combined with hydrochlorothiazide 160 mg125 mg at the end of the 10-week study using a closed testing procedure first testing for non-inferiority based on SBP if significant testing for non-inferiority based on DBP if significant testing for superiority based on SBP and if significant testing for superiority based on DBP
Secondary Endpoints
Statistically greater reductions in ambulatory blood pressure for patients treated with telmisartan combined with hydrochlorothiazide 80 mg125 mg compared to patients treated with valsartan combined with hydrochlorothiazide 160 mg125 mg at the end of the 10-week study as measured by 1 Changes from baseline in the last 6 hours of the 24-hour dosing interval for pulse pressure 2 Changes from baseline in the 24-hour ABPM mean relative to dose time for SBP DBP and pulse pressure 3 Changes from baseline in the ABPM mean SBP DBP and pulse pressure relative to clock time during other periods ie morning daytime night time of the 24-hour dosing interval 4 Change from baseline in systolic and diastolic blood pressure load during the 24-hour dosing interval and 5 Percentage of patients responding to treatment based on the 24-hour ABPM mean SBP and DBP relative to dose time
Statistically greater reduction in mean seated trough blood pressure patients treated with telmisartan combined with hydrochlorothiazide 80 mg125 mg compared to patients treated with valsartan combined with hydrochlorothiazide 160 mg125 mg at the end of the 10-week study as measured by 1 Changes from baseline in mean seated trough SBP and DBP as determined by electronic or manual device in-clinic and 2 Percentage of patients responding to treatment based on electronic or manual in-clinic trough cuff blood pressures
Evaluation of other endpoints comparing telmisartan combined with hydrochlorothiazide 80 mg125 mg to valsartan combined with hydrochlorothiazide 160 mg125 mg respectively including 1 Changes from baseline in metabolic markers serum TG LDL-C HDL-C total cholesterol potassium fasting glucose and HbA1C and for urine Na K Cl proteinuria as measured by spot urine for proteincreatinine ratio and 2 inflammatory markers serum high sensitive C-reactive protein serum homocysteine and plasma fibrinogen
Criteria for Safety
Evaluation of adverse events physical examinations laboratory assessments pulse rate and cuff blood pressure monitoring
Statistical Method
Analysis of covariance with treatment and centre as main effects and baseline as a covariate Mantel-Haenszel test controlling for centre
Study Hypothesis
Null Hypothesis
The overall mean change from baseline in the automated blood pressure monitor mean blood pressure during the last 6 hours of the 24-hour dosing interval for telmisartan 80 mg plus hydrochlorothiazide 125 mg is less than or equal to that for valsartan 160 mg plus hydrochlorothiazide 125 mg
Alternative Hypothesis
The overall mean change from baseline in the automated blood pressure monitor mean blood pressure during the last 6 hours of the 24-hour dosing interval for telmisartan 80 mg plus hydrochlorothiazide 125 mg is greater than that for valsartan 160 mg plus hydrochlorothiazide 125 mg
Comparisons
Telmisartan 80 mg plus hydrochlorothiazide 125 mg vs valsartan 160 mg plus hydrochlorothiazide 125 mg
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