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Efficacy of Aliskiren Compared to Ramipril in the Treatment of Moderate Systolic Hypertensive Patients (ALIAS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT01042392
First received: January 1, 2010
Last updated: March 6, 2012
Last verified: March 2012
History of Changes
  Purpose

This prospective multicenter, double blind study will evaluate the efficacy and safety of aliskiren versus ramipril in patients with moderate systolic essential hypertension.


Condition Intervention Phase
Essential Hypertension
 Drug: Aliskiren
Drug: Ramipril
Drug: Matching placebo to Aliskiren
Drug: Matching placebo to Ramipril
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy of Aliskiren Compared to Ramipril in the Treatment of Moderate Systolic Hypertensive Patients

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) [ Time Frame: Baseline to 8 weeks ] [ Designated as safety issue: No ]
    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:
  • Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) [ Time Frame: Baseline to 8 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: At 4 and 8 weeks ] [ Designated as safety issue: No ]

    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 [ Time Frame: After 8 weeks ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to 4 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: At week 8 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to 8 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: From 8 weeks to 48 hours after week 8 ] [ Designated as safety issue: No ]
    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) [ Time Frame: 8 weeks + 1 day ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 506
Study Start Date: November 2009
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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).

 Drug: Ramipril
Ramipril 5 mg was given in capsule form.
Other Name: Ramipril
Drug: Matching placebo to Aliskiren
The tablet of matching placebo to aliskiren 150 mg for period I and III. In period II, matching placebo to Aliskiren was given to Ramipril active treatment arm.
Experimental: 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).

 Drug: Aliskiren
150 mg Aliskiren as film-coated tablet
Other Name: Aliskiren
Drug: Matching placebo to Ramipril
The placebo capsule to ramipril 5 mg for period I and III. In period II, matching placebo to Ramipril was given to Aliskiren active treatment arm.
Placebo Comparator: 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).
 Drug: Matching placebo to Ramipril
The placebo capsule to ramipril 5 mg for period I and III. In period II, matching placebo to Ramipril was given to Aliskiren active treatment arm.
Placebo Comparator: 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).
 Drug: Matching placebo to Aliskiren
The tablet of matching placebo to aliskiren 150 mg for period I and III. In period II, matching placebo to Aliskiren was given to Ramipril active treatment arm.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01042392

  Show 99 Study Locations
Sponsors and Collaborators
Novartis
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT01042392     History of Changes
Other Study ID Numbers: CSPP100AFR01, 2009-011296-80
Study First Received: January 1, 2010
Results First Received: January 12, 2012
Last Updated: March 6, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Novartis:
Moderate systolic hypertension - adults - aliskiren -ramipril

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Ramipril
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
 Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 16, 2013