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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Aliskiren; Drug: Placebo to Aliskiren; Drug: Telmisartan; Drug: Placebo to Telmisartan

• Study Type: Interventional
• Enrollment (Actual): 822
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Sorocaba, Brazil
    • Investigative Site
• Canada
  • Gatineau, Canada
    • Investigative Site
• Ecuador
  • Guayaquil, Ecuador
    • Investigative Site
• Germany
  • Erfurt, Germany
    • Investigative Site
• Hungary
  • Budapest, Hungary
    • Invesitagtive Site
• Korea, Republic of
  • Cheongju, Korea, Republic of
    • Investigative Site
• Malaysia
  • Kuala Lumpur, Malaysia
    • Investigative Site
• Mexico
  • Mexico City, Mexico
    • Investigative Site
• Panama
  • Panama City, Panama
    • Investigative Site
• Philippines
  • Manila, Philippines
    • Investigative Site
• Singapore
  • Singapore, Singapore
    • Investigative Site
• Slovakia
  • Bratislava, Slovakia
    • Investigative Site
• Spain
  • Sevilla, Spain
    • Investigative Site
• Turkey
  • Istanbul, Turkey
    • Investigative Site
• United Kingdom
  • Westbury, United Kingdom
    • Investigative Site
• Venezuela
  • Caracas, Venezuela
    • Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aliskiren 300 mg; 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; Aliskiren 150 mg tablets taken orally daily. 1 tablet for the first two weeks followed by 2 tablets for 10 weeks.; Drug: Placebo to Aliskiren; Placebo to Aliskiren tablets taken orally daily. 1 Tablet for the first 2 weeks and 2 tablets during the no treatment (withdrawal) week.
Active Comparator: Telmisartan 80 mg; 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; Telmisartan 40 mg capsules taken orally daily. 1 capsule the first 2 weeks followed by 2 capsules for 10 weeks.; Drug: Placebo to Telmisartan; Placebo to Telmisartan capsule taken orally daily. 1 capsule for the first 2 weeks and 2 capsules during the no treatment (withdrawal) week.

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

Collaborators and Investigators

• Sponsor: Novartis

Publications and helpful links

General Publications

• Williams B, Lacy PS, Baschiera F, Brunel P, Dusing R. Novel description of the 24-hour circadian rhythms of brachial versus central aortic blood pressure and the impact of blood pressure treatment in a randomized controlled clinical trial: The Ambulatory Central Aortic Pressure (AmCAP) Study. Hypertension. 2013 Jun;61(6):1168-76. doi: 10.1161/HYPERTENSIONAHA.111.00763. Epub 2013 Apr 29.
• Dusing R, Brunel P, Baek I, Baschiera F. Sustained blood pressure-lowering effect of aliskiren compared with telmisartan after a single missed dose. J Clin Hypertens (Greenwich). 2013 Jan;15(1):41-7. doi: 10.1111/jch.12018. Epub 2012 Oct 9.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: March 17, 2009
• First Submitted That Met QC Criteria: March 18, 2009
• First Posted (Estimate): March 19, 2009

Study Record Updates

• Last Update Posted (Estimate): July 22, 2011
• Last Update Submitted That Met QC Criteria: June 22, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: ABPM; Hypertension; cardiovascular disease; systolic blood pressure; diastolic blood pressure; aliskiren; telmisartan
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Telmisartan
• Other Study ID Numbers: CSPP100A2408