Efficacy and Safety of Aliskiren in Patients With Mild to Moderate Hypertension During Exercise

An Eight-week, Randomized, Double-blind, Parallel-group, Pilot Study to Evaluate the Efficacy and Safety of Aliskiren 300 mg in Comparison With Valsartan 320 mg in Patients With Mild to Moderate Hypertension During Exercise After a Missed Dose

This study compared the blunting effect of aliskiren and valsartan monotherapies on exercise-induced rises in systolic blood pressure in patients with mild to moderate essential hypertension.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Aliskiren; Drug: Placebo to aliskiren; Drug: Placebo to valsartan; Drug: Valsartan

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czech Republic
  • Pardubice, Czech Republic
    • Investigative Site
  • Prague, Czech Republic
    • Investigative Site
• Hungary
  • Budapest, Hungary
    • Investigative Site
  • Nyiregyhaza, Hungary
    • Investigative Site
  • Pilisvörösvár, Hungary
    • Investigative Site
  • Szentendre, Hungary
    • Investigative Site
• Singapore
  • Singapore, Singapore
    • Investigative Site
• United Kingdom
  • Leicester, United Kingdom
    • Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 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 measured at rest
• Patients able to exercise and to reach 85% of their predicted heart rate during a standard exercise test on a treadmill according to the Bruce Protocol

Exclusion criteria:

• Patients not confident in exercising or not able to exercise
• Absolute contraindication to exercise
• Mean sitting systolic blood pressure ≥ 180 mmHg and/or mean sitting diastolic blood pressure ≥ 110 mmHg measured at rest

Other protocol-defined inclusion/exclusion criteria applied to the study.

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; For the first week of the 8 week treatment period, patients received aliskiren 150 mg, placebo to aliskiren, and 2 capsules of placebo to valsartan. For the remaining 7 weeks of the study, patients received aliskiren 300 mg (two 150 mg tablets) and 2 capsules of placebo to valsartan. The tablets and capsules (2 of each) were taken orally once daily each morning. To evaluate a missed dose, the last dose of medication was administered at the clinic, and the patient was scheduled to return 2 days later for exercise testing (8 weeks + 2 days).	Drug: Aliskiren; Aliskiren was supplied in 150 mg tablets.; Drug: Placebo to aliskiren; Placebo to aliskiren was supplied in tablets matching aliskiren 150 mg.; Drug: Placebo to valsartan; Placebo to valsartan was supplied in capsules matching valsartan 160 mg.
Active Comparator: Valsartan; For the first week of the 8 week treatment period, patients received valsartan 160 mg, placebo to valsartan, and 2 tablets of placebo to aliskiren. For the remaining 7 weeks of the study, patients received valsartan 320 mg (two 160 mg capsules) and 2 tablets of placebo to aliskiren. The tablets and capsules (2 of each) were taken orally once daily each morning. To evaluate a missed dose, the last dose of medication was administered at the clinic, and the patient was scheduled to return 2 days later for exercise testing (8 weeks + 2 days).	Drug: Placebo to aliskiren; Placebo to aliskiren was supplied in tablets matching aliskiren 150 mg.; Drug: Placebo to valsartan; Placebo to valsartan was supplied in capsules matching valsartan 160 mg.; Drug: Valsartan; Valsartan was supplied in 160 mg capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Resting vs. Peak Heart Rate Systolic Blood Pressure (SBP) From Baseline to Week 8 After a Missed Dose	The difference in resting vs. peak (85% of maximal predicted) heart rate (HR) SBP was calculated by measuring SBP before and during exercise on a standardized treadmill test, conducted according to the Bruce Protocol. Treadmill speed and incline were increased every 3 minutes until the patient was exhausted or peak HR was reached. The SBP at rest vs peak HR was recorded at Baseline and at Week 8 + 2 days (24-hrs after a missed dose); the change in rest vs. peak SBP between these timepoints is reported. The analysis included the rest to peak increase in SBP at baseline as a covariate.	Baseline and Week 8 + 2 days (48-hours after the last dose; 24 hours after a missed dose). Blood Pressure measurements were taken at rest and at peak heart rate at both timepoints.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Resting vs. Peak Heart Rate Systolic Blood Pressure (SBP) From Baseline to Week 8	The difference in resting vs. peak (85% of the maximal predicted) heart rate (HR) SBP was calculated by measuring SBP before and during exercise on a standardized treadmill test, conducted according to the Bruce Protocol. Treadmill speed and incline were increased every 3 minutes until the patient was exhausted or peak HR was reached. The SBP at rest vs peak HR was recorded at Baseline and at Week 8 (end of active treatment); the change in SBP between these timepoints is reported. The analysis included the rest to peak increase in SBP at baseline as a covariate.	Baseline and Week 8 (end of active treatment). Blood Pressure measurements were taken at rest and at peak heart rate at both timepoints.
Change in Resting vs. Peak Heart Rate Systolic Blood Pressure (SBP) From Week 8 (End of Active Treatment) to 24-hours After a Missed Dose	The difference in resting vs. peak (85% of maximal predicted) heart rate (HR) SBP was calculated by measuring SBP before and during exercise on a standardized treadmill test, conducted according to the Bruce Protocol. The SBP at rest vs peak HR was recorded at Week 8 (end of active treatment) and Week 8 + 2 days (48-hrs after last dose; 24-hrs after missed dose); the change in rest vs. peak SBP between these timepoints is reported. The analysis included the rest to peak increase in SBP at baseline as a covariate.	Week 8 (Last dose; end of active treatment) and Week 8 + 2 days (48-hours after the last dose; 24 hours after a missed dose). Blood Pressure measurements were taken at rest and at peak heart rate at both timepoints.

Collaborators and Investigators

• Sponsor: Novartis

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: January 7, 2009
• First Submitted That Met QC Criteria: January 8, 2009
• First Posted (Estimate): January 9, 2009

Study Record Updates

• Last Update Posted (Estimate): June 28, 2011
• Last Update Submitted That Met QC Criteria: June 2, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: hypertension; cardiovascular disease; exercise test; systolic blood pressure; aliskiren; valsartan
• 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; Valsartan
• Other Study ID Numbers: CSPP100A2406