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

Essential Hypertension Clinical Trial

— ALIAS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01042392
• Other study ID #: CSPP100AFR01
• Secondary ID: 2009-011296-80
• Status: Completed
• Phase: Phase 4
• First received: January 1, 2010
• Last updated: March 6, 2012
• Start date: November 2009
• Est. completion date: January 2011

Study information

• Verified date: March 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 506
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Essential Hypertension
• Hypertension

Intervention

Drug:
• Aliskiren
150 mg Aliskiren as film-coated tablet
• Ramipril
Ramipril 5 mg was given in capsule form.
• 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.
• 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.

Locations

Country	Name	City	State
France	Novartis Investigative Site	Aire Sur Adour
France	Novartis Investigative Site	Amboise
France	Novartis Investigative Site	Angers
France	Novartis Investigative Site	Anzin
France	Novartis Investigative Site	Bachant
France	Novartis Investigative Site	Bandol
France	Novartis Investigative Site	Becon-les-granits
France	Novartis Investigative Site	Bersee
France	Novartis Investigative Site	Bordeaux
France	Novartis Investigative Site	Bouliac
France	Novartis Investigative Site	Bourges
France	Novartis Investigative Site	Briollay
France	Novartis Investigative Site	Bruges
France	Novartis Investigative Site	Caen
France	Novartis Investigative Site	Carbonne
France	Novartis Investigative Site	Château Gontier
France	Novartis Investigative Site	Château-gontier
France	Novartis Investigative Site	Chatellerault
France	Novartis Investigative Site	Chatillon Sur Colmon
France	Novartis Investigative Site	Cherbourg
France	Novartis Investigative Site	Cournonterral
France	Novartis Investigative Site	Croix
France	Novartis Investigative Site	Cugnaux
France	Novartis Investigative Site	Ecouflant
France	Novartis Investigative Site	Equeurdreville
France	Novartis Investigative Site	Falaise
France	Novartis Investigative Site	Fondettes
France	Novartis Investigative Site	Guerigny
France	Novartis Investigative Site	Hautmont
France	Novartis Investigative Site	L'aigle
France	Novartis Investigative Site	La Farlede
France	Novartis Investigative Site	La Riche
France	Novartis Investigative Site	La Rochelle
France	Novartis Investigative Site	Labarthe Sur Leze
France	Novartis Investigative Site	Lambersart
France	Novartis Investigative Site	Laval
France	Novartis Investigative Site	Le Bouscat
France	Novartis Investigative Site	Le Cailar
France	Novartis Investigative Site	Le Fousseret
France	Novartis Investigative Site	Le Pradet
France	Novartis Investigative Site	Les Maguelone
France	Novartis Investigative Site	Luynes
France	Novartis Investigative Site	Marcheprime
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Marsilly
France	Novartis Investigator Site	Marsilly
France	Novartis Investigative Site	Mayenne
France	Novartis Investigative Site	Medis
France	Novartis Investigative Site	Mont-de-marsan
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Montrevault
France	Novartis Investigative Site	Monts sur guesnes
France	Novartis Investigative Site	Mortagne-sur-sevre
France	Novartis Investigative Site	Mourmelon-le-petit
France	Novartis Investigative Site	Nantes
France	Novartis Investigative Site	Nevers
France	Novartis Investigative Site	Nieul sur mer
France	Novartis Investigative Site	Orchies
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Perigny
France	Novartis Investigative Site	Potigny
France	Novartis Investigative Site	Reims
France	Novartis Investigative Site	Roquevaire
France	Novartis Investigative Site	Rouen
France	Novartis Investigative Site	Saint Avertin
France	Novartis Investigative Site	Saint Benoit
France	Novartis Investigative Site	Saint Germain de marencennes
France	Novartis Investigative Site	Saint loubes
France	Novartis Investigative Site	Saint Rogatien
France	Novartis Investigative Site	Saint Xandre
France	Novartis Investigative Site	Saint-CYR-SUR-MER
France	Investigative Site	Saint-orens-de-gameville
France	Novartis Investigative Site	Saint-orens-de-gameville
France	Novartis Investigative Site	Sainte marie de re
France	Novartis Investigative Site	Sanary sur mer
France	Novartis Investigative Site	Savonnieres
France	Novartis Investigative Site	Scorbe clairvaux
France	Investigative Site	Scorbe-clairvaux
France	Novartis Investigative Site	Segre
France	Novartis Investigative Site	Seysses
France	Novartis Investigative Site	Sotteville les rouen
France	Novartis Investigative Site	ST Cyr Sur Loire
France	Novartis Investigative Site	St Georges D'Orques
France	Novartis Investigative Site	St Martin D'Oney
France	Novartis Investigative Site	St Seurin De Cursac
France	Novartis Investigative Site	Strasbourg
France	Novartis Investigative Site	Thun St Amand
France	Novartis Investigative Site	Tierce
France	Investigative Site	Toulon
France	Novartis Investigative Site	Toulon
France	Novartis Investigative Site	Toulouse
France	Novartis Investigative Site	Tours
France	Novartis Investigative Site	Trelaze
France	Novartis Investigative Site	Vendome
France	Novartis Investigative Site	Vereneque
France	Novartis Investigative Site	Verzy
France	Novartis Investigative Site	Vierzon
France	Novartis Investigative Site	Vieux Conde
France	Novartis Investigative Site	Witry-Les-Reims

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)	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.	Baseline to 8 weeks	No
Secondary	Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)	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.	Baseline to 8 weeks	No
Secondary	Percentage of Patients With Controlled Blood Pressure	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.	At 4 and 8 weeks	No
Secondary	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	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.	After 8 weeks	No
Secondary	Change in msSBP and msDBP From Visit 2 (Baseline) to Visit 3 (at 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.	Baseline to 4 weeks	No
Secondary	Difference Between the Maximal and the Minimal Mean-hour SPB Measured Between 1 and 8 am 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.	At week 8	No
Secondary	Change in Mean Sitting DBP and SBP in Specified Sub-groups From Visit 2 (Baseline) to Visit 4 (at 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%.	Baseline to 8 weeks	No
Secondary	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	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.	From 8 weeks to 48 hours after week 8	No
Secondary	Number Patients Reported With Adverse Events (AEs), Serious Adverse Events (SAE) and Death (Period II and Period III)	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.	8 weeks + 1 day	Yes