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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Aliskiren
* Drug: Valsartan
* Drug: Placebo to aliskiren
* Drug: Placebo to valsartan


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aliskiren<br>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<br>* Aliskiren was supplied in 150 mg tablets.<br>Drug: Placebo to aliskiren<br>* Placebo to aliskiren was supplied in tablets matching aliskiren 150 mg.<br>Drug: Placebo to valsartan<br>* Placebo to valsartan was supplied in capsules matching valsartan 160 mg.<br>|
| Active Comparator: Valsartan<br>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: Valsartan<br>* Valsartan was supplied in 160 mg capsules.<br>Drug: Placebo to aliskiren<br>* Placebo to aliskiren was supplied in tablets matching aliskiren 150 mg.<br>Drug: Placebo to valsartan<br>* Placebo to valsartan was supplied in capsules matching valsartan 160 mg.<br>|

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aliskiren, hypertension, systolic blood pressure, exercise test, cardiovascular disease, valsartan