Efficacy and Safety of Aliskiren 300 mg Compared to Telmisartan 80 mg After 1 Week of Treatment Withdrawal

Study Overview
=================
Brief Summary
-----------------
This study was specifically designed to provide additional information on the mechanism of action of direct renin inhibition postulating the higher-level RAS cascade inhibition. The purpose of this study was to compare the prolonged efficacy and safety of aliskiren to that of telmisartan in mild to moderate hypertensive patients in the 24 hrs Ambulatory Blood Pressure Monitoring setting after a one week treatment withdrawal.

Official Title
-----------------
A Twelve-week, Randomized, Double-blind, Parallel Group Study to Evaluate the Prolonged Efficacy and Safety of Aliskiren 300 mg Compared to Telmisartan 80 mg in Mild to Moderate Hypertensive Patients With the 24-hour Ambulatory Blood Pressure Measurement After 1 Week of Treatment Withdrawal Study Acronym: ASSERTIVE - AliSkiren Study of Profound antihypERtensive Efficacy in hyperTensIVE Patients

Conditions
-----------------
Hypertension

Intervention / Treatment
-----------------
* Drug: Aliskiren
* Drug: Telmisartan
* Drug: Placebo to Aliskiren
* Drug: Placebo to Telmisartan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Mean sitting systolic blood pressure ≥ 140 mmHg and < 180 mmHg 24-hr mean ambulatory systolic blood pressure ≥ 135 mmHg Exclusion Criteria: Severe hypertension defined as mean sitting systolic blood pressure ≥ 180 mmHg and/or mean sitting diastolic blood pressure ≥ 110 mmHg Patients with Type 1 diabetes mellitus Secondary hypertension of any etiology Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aliskiren 300 mg<br>Aliskiren tablets starting at a dose of 150 mg taken orally daily for 2 weeks followed by a dose of 300 mg taken orally for 10 weeks and placebo (withdrawal) for one week. Participants took Placebo to Aliskiren: 1 tablet for the first 2 weeks and 2 tablets during the one week withdrawal period. | Drug: Aliskiren<br>* Aliskiren 150 mg tablets taken orally daily. 1 tablet for the first two weeks followed by 2 tablets for 10 weeks.<br>Drug: Placebo to Aliskiren<br>* Placebo to Aliskiren tablets taken orally daily. 1 Tablet for the first 2 weeks and 2 tablets during the no treatment (withdrawal) week.<br>|
| Active Comparator: Telmisartan 80 mg<br>Telmisartan capsules starting at a dose of 40 mg taken orally daily for 2 weeks followed by a dose of 80 mg taken orally daily for 10 weeks and placebo (withdrawal) for one week. Participants took Placebo to Telmisartan: 1 capsule for the first 2 weeks and 2 capsules during the one week withdrawal period. | Drug: Telmisartan<br>* Telmisartan 40 mg capsules taken orally daily. 1 capsule the first 2 weeks followed by 2 capsules for 10 weeks.<br>Drug: Placebo to Telmisartan<br>* Placebo to Telmisartan capsule taken orally daily. 1 capsule for the first 2 weeks and 2 capsules during the no treatment (withdrawal) week.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 24 Hour (24-Hr) Mean Ambulatory Systolic Blood Pressure (MASBP) From the End of the Active Treatment Period to Day 7 of the Withdrawal Period | An Ambulatory Blood Pressure Monitor measured a participants's blood pressure over a 24 hour period using an automated validated monitoring device at week 12 (end of the active treatment) and at week 13 (end of the day 7 withdrawal period). The 24 Hour MASBP was calculated by taking the mean of all Ambulatory Systolic Blood Pressure readings for the 24 hour period. The difference of the 24 hour MASBP from the end of the active treatment to Day 7 of the treatment withdrawal period was calculated using a two way analysis of variance with treatment and region as factors. | 12 weeks, 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 24 Hour (24-hr) Mean Ambulatory Diastolic Blood Pressure (MADBP) From the End of the Active Treatment Period to Day 7 of the Withdrawal Period | An Ambulatory Blood Pressure Monitor measured a participants's blood pressure over a 24 hour period using an automated validated monitoring device at week 12 (end of the active treatment) and at week 13 (end of the day 7 withdrawal period). The 24 Hour MADBP was calculated by taking the mean of all Ambulatory Diastolic Blood Pressure readings for the 24 hour period. The difference of the 24 hour MADBP from the end of the active treatment to Day 7 of the withdrawal period was calculated using a two way analysis of variance with treatment and region as factors. | 12 weeks, 13 weeks | 
| Change in 24-hr Mean Ambulatory Systolic Blood Pressure (MASBP) and Mean Ambulatory Diastolic Blood Pressure (MADBP) From Baseline to Day 7 of the Withdrawal Period | An Ambulatory Blood Pressure Monitor measured a participants's blood pressure over a 24 hour period using an automated validated monitoring device at Baseline (at Randomization) and at week 13 (day 7 of the withdrawal period). The 4 Hour MASBP and MADBP was calculated by taking the mean of all Ambulatory Blood Pressure readings during the 24 hour period. The difference of the 24 hour measurements from baseline to day 7 of the withdrawal period were calculated using a two way analysis of variance with treatment and region as factors and baseline as a covariate. | Baseline, 13 weeks | 
| Change in the Mean Sitting Systolic Blood Pressure (msSBP) as Measured at All Study Visits During the Double-blind Treatment Period and During the Treatment Withdrawal Period | Blood Pressure was measured in the office after the patient was sitting for 5 minutes. The average of 3 readings 1-2 minutes apart were used in the analysis. The change in the double-blind period was calculated from the end of active treatment at week 12 to the Baseline (Randomization) using Analysis of Covariance with treatment and region as factors and baseline msSBP as a covariate. The change in the treatment interruption period was calculated from day 7 of the withdrawal period at week 13 to the end of the active treatment using Analysis of Variance with treatment and region as factors. | Baseline, 12 weeks, 13 weeks | 
| Change in the Mean Diastolic Sitting Blood Pressure (msDBP) as Measured at All Study Visits During the Double-blind Treatment Period and During the Treatment Withdrawal Period | Blood Pressure was measured in the office after the patient was sitting for 5 minutes. The average of 3 readings 1-2 min. apart were used in the analysis. The change in the double-blind period was calculated from the end of active treatment at week 12 to the Baseline (Randomization) using Analysis of Covariance with treatment and region as factors and baseline msDBP as a covariate. The change in the treatment interruption period was calculated from day 7 of the withdrawal period at week 13 to the end of the active treatment using Analysis of Variance with treatment and region as factors. | Baseline, 12 weeks, 13 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hypertension, ABPM, systolic blood pressure, diastolic blood pressure, cardiovascular disease, aliskiren, telmisartan