Efficacy of Aliskiren Compared to Ramipril in the Treatment of Moderate Systolic Hypertensive Patients
- Conditions
- Essential Hypertension
- Interventions
- Registration Number
- NCT01042392
- Lead Sponsor
- Novartis
- Brief Summary
This prospective multicenter, double blind study will evaluate the efficacy and safety of aliskiren versus ramipril in patients with moderate systolic essential hypertension.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 506
-
Outpatients > 18 years
-
Male or female patients. Female patients must have been either post-menopausal for one year, surgically sterile, or using effective contraceptive methods
-
Patients with essential hypertension, previously treated with an antihypertensive single-drug therapy, either uncontrolled or intolerant.
-
BP thresholds at visit 1:
- For patients previously treated and uncontrolled: 140≤ office SBP<180 mmHg
- For patients previously treated, controlled but intolerant: office SBP≥130 mmHg
-
BP thresholds at visit 2 (for all patients):
- 160≤office SBP<180 mmHg AND
- 155≤home SBP<175 mmHg (3-day period of home blood pressure monitoring just before randomization)
- Women of child-bearing potential not using any effective methods of contraception
- Severe hypertension (office BP ≥ 180/110 mmHg)
- Impossibility to stop abruptly previous antihypertensive treatments at visit 1
- Patients previously untreated or patients treated with two or three antihypertensive medications
- History or evidence of a secondary form of hypertension
- History of hypersensitivity to ACEi or renin inhibitors
- History of heart failure, stroke or coronary heart disease
- Serum potassium ≥ 5.2 mmol/l
Other protocol-defined inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ramipril Matching placebo to Aliskiren In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal): At visit 4, part of patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4). Aliskiren Matching placebo to Ramipril In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal ): At visit 4, part of the patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4). Placebo to Ramipril Matching placebo to Ramipril In period III (double-blind withdrawal ): At visit 4, part of patients from Ramipril arm received placebo to Ramipril for 1 day. The study ended at visit 5 (48 hours later than visit 4). Placebo to Aliskiren Matching placebo to Aliskiren In period III (double-blind withdrawal ): At visit 4, part of the patients from Aliskiren arm received placebo to Aliskiren for 1 day. The study ended at visit 5 (48 hours later than visit 4). Ramipril Ramipril In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Ramipril 5 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to Ramipril 10 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal): At visit 4, part of patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4). Aliskiren Aliskiren In period I (washout and single-blind): from visit 1 to visit 2, 2 weeks placebo run-in. In period II (double-blind treatment, randomized): Aliskiren 150 mg for 4 weeks (visit 2 - visit 3). At visit 3, medications had to be titrated to aliskiren 300 mg only if BP remained ≥ 140/90 mmHg. Double blind treatment had to be continued for another 4-week period until visit 4. In period III (double-blind withdrawal ): At visit 4, part of the patients received the active treatment for 1 day. The study ended at visit 5 (48 hours later than visit 4).
- Primary Outcome Measures
Name Time Method Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) Baseline to 8 weeks The arm in which the highest sitting systolic blood pressure (SBP) was found at study entry was used for all subsequent readings. At each study visit, after leaving the patient to rest 5 minutes in a sitting position, the blood pressure (BP) was measured three times with an oscillometric device. The measurements were performed at 1-2 minute intervals. The mean BP was calculated from the 3 readings. The analysis of covariance included treatment factor and baseline mean sitting SBP as covariable.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) Baseline to 8 weeks The arm in which the highest sitting systolic blood pressure (SBP) was found at study entry was used for all subsequent readings. At each study visit, after leaving the patient to rest 5 minutes in a sitting position, the blood pressure (BP) was measured three times with an oscillometric device. The measurements were performed at 1-2 minute intervals. The mean BP was calculated from the 3 readings. The analysis of variance included treatment factor and baseline value of mean sitting DBP as covariable.
Percentage of Patients With Controlled Blood Pressure At 4 and 8 weeks The arm in which the highest sitting systolic blood pressure (SBP) was found at study entry was used for all subsequent readings. At each study visit, after leaving the patient to rest 5 minutes in a sitting position, the blood pressure (BP) was measured three times with an oscillometric device. The measurements were performed at 1-2 minute intervals. The mean BP was calculated from the 3 readings.
Controlled blood pressure (BP) is defined as mean office systolic BP/ diastolic BP \< 140/90 mmHg.Number of the Participants With More Than 55 mmHg Difference Between the Mean SBP Measured at the Morning Surge and the Mean Minimal SBP Measured During the Night After 8 weeks Ambulatory blood pressure measurement (ABPM) over 24 hours was performed for all patients on the day before visit 4, the device attached to the ambulatory blood pressure non-dominant arm of the patient. The BP morning surge was defined as the average of the measurements taken during the first 2 hours after waking the patient. The minimal night blood pressure was defined as the average of the two lowest BP measures (the lowest hourly average) recorded during night time.
Change in msSBP and msDBP From Visit 2 (Baseline) to Visit 3 (at 4 Weeks) Baseline to 4 weeks The arm in which the highest sitting systolic blood pressure (SBP) was found at study entry was used for all subsequent readings. At each study visit, after leaving the patient to rest 5 minutes in a sitting position, the blood pressure (BP) was measured three times with an oscillometric device. The measurements were performed at 1-2 minute intervals. The mean BP was calculated from the 3 readings. The analysis of covariance included treatment factor and baseline mean sitting SBP and mean sitting DBP as covariables.
Difference Between the Maximal and the Minimal Mean-hour SPB Measured Between 1 and 8 am at Week 8 At week 8 Ambulatory blood pressure measurement (ABPM) over 24 hours was performed for all patients on the eve of visit 4 (week 8), the device attached to the ambulatory blood pressure non-dominant arm of the patient. The difference between mean-hour maximum SBP mean-hour minimum SBP between 1 am and 8 am was measured.
Change in Mean Sitting DBP and SBP in Specified Sub-groups From Visit 2 (Baseline) to Visit 4 (at 8 Weeks) Baseline to 8 weeks The sub-groups were: "Riser" = patients with \>= 55 mmHg difference between the mean SPB measured at the morning surge and the mean minimal SBP measured during the night. The "Non-risers" in whom the difference is \<55 mmHg. Patients called "dippers" in whom there was a decrease in average nocturnal SBP ≥ 10% compared with average daytime SBP, in contrast to patients "non-dippers " in whom this difference was \<10%.
Change in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) From Last Active Dose Taken to After a One-day Missed-dose From 8 weeks to 48 hours after week 8 The change in blood pressure was measured between visit 4 (end of the period of double-blind active treatment which was at week 8) and visit 5 (48 hours after the last active dose taken) in the group of patients who received aliskiren or placebo and those who received ramipril or placebo. The analysis of covariance included treatment factor and baseline mean sitting SBP and mean sitting DBP as covariables.
Number Patients Reported With Adverse Events (AEs), Serious Adverse Events (SAE) and Death (Period II and Period III) 8 weeks + 1 day Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Trial Locations
- Locations (3)
Novartis Investigative Site
🇫🇷Witry-Les-Reims, France
Novartis Investigator Site
🇫🇷Marsilly, France
Investigative Site
🇫🇷Toulon, France