Safety and Efficacy of Aliskiren on the Progression of Atherosclerosis in Coronary Artery Disease Patients (AQUARIUS)

A 104 Week, Randomized, Double Blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy of Aliskiren on the Progression of Atherosclerosis in Patients With Coronary Artery Disease When Added to Optimal Background Therapy

The study will assess the change in coronary atherosclerotic disease as determined by intravascular ultrasound (IVUS) for aliskiren compared to placebo when given in addition to standard therapy in patients with coronary artery disease (CAD) and a blood pressure in the pre-hypertensive range.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease (CAD); Coronary Atherosclerosis
• Intervention / Treatment: Drug: Placebo; Drug: Aliskiren

• Study Type: Interventional
• Enrollment (Actual): 613
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1428DCO
    • Novartis Investigative Site
  • Buenos Aires, Argentina, C1039AAP
    • Novartis Investigative Site
  • Buenos Aires, Argentina, C1280AEB
    • Novartis Investigative Site
  • Buenos Aires, Argentina, C1426ANZ
    • Novartis Investigative Site
  • Buenos aires, Argentina, C1210AAP
    • Novartis Investigative Site
  • Corrientes, Argentina, 3400
    • Novartis Investigative Site
  • Capital Federal
    • Buenos Aires, Capital Federal, Argentina, C1180AAX
      • Novartis Investigative Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina, C2000DSR
      • Novartis Investigative Site
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Novartis Investigative Site
    • Liverpool, New South Wales, Australia, 2170
      • Novartis Investigative Site
    • New Lambton Heights, New South Wales, Australia, 2305
      • Novartis Investigative Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Novartis Investigative Site
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Novartis Investigative Site
• Belgium
  • Aalst, Belgium, 9300
    • Novartis Investigative Site
  • Anderlecht, Belgium, 1070
    • Novartis Investigative Site
  • Brussel, Belgium, 1000
    • Novartis Investigative Site
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
  • Charleroi, Belgium, 6000
    • Novartis Investigative Site
  • Genk, Belgium, 3600
    • Novartis Investigative Site
  • Ottignies, Belgium, 1340
    • Novartis Investigative Site
• Canada
  • Quebec, Canada, G1V 4G5
    • Novartis Investigative Site
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Novartis Investigative Site
    • Edmonton, Alberta, Canada, T5H 3V9
      • Novartis Investigative Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 3C3
      • Novartis Investigative Site
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Novartis Investigative Site
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 5H6
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H1T 2M4
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H1T 1C8
      • Novartis Investigative Site
• France
  • Creteil, France, 94010
    • Novartis Investigative Site
  • Le Plessis Robinson, France, 92350
    • Novartis Investigative Site
  • Pessac Cedex, France, 33604
    • Novartis Investigative Site
  • Toulouse Cedex, France, 31059
    • Novartis Investigative Site
• Germany
  • Coburg, Germany, 96450
    • Novartis Investigative Site
  • Essen, Germany, 45122
    • Novartis Investigative Site
  • Frankfurt, Germany, 60316
    • Novartis Investigative Site
  • Hamburg, Germany, 20246
    • Novartis Investigative Site
  • Hamburg, Germany, 20099
    • Novartis Investigative Site
  • Leipzig, Germany, 04289
    • Novartis Investigative Site
  • Ludwigshafen, Germany, 67063
    • Novartis Investigative Site
  • Muenchen, Germany, 81737
    • Novartis Investigative Site
  • Neuss, Germany, 41464
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1134
    • Novartis Investigative Site
  • Budapest, Hungary, 1122
    • Novartis Investigative Site
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
  • Szeged, Hungary, 6720
    • Novartis Investigative Site
  • Baranya
    • Pecs, Baranya, Hungary, 7621
      • Novartis Investigative Site
• Italy
  • Novara, Italy, 28100
    • Novartis Investigative Site
  • AR
    • Arezzo, AR, Italy, 52100
      • Novartis Investigative Site
  • BG
    • Bergamo, BG, Italy, 24128
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20132
      • Novartis Investigative Site
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
    • Sesto San Giovanni, MI, Italy, 20099
      • Novartis Investigative Site
  • MS
    • Massa, MS, Italy, 54100
      • Novartis Investigative Site
  • PR
    • Parma, PR, Italy, 43100
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00185
      • Novartis Investigative Site
  • SI
    • Siena, SI, Italy, 53100
      • Novartis Investigative Site
• Poland
  • Bialystok, Poland, 15-276
    • Novartis Investigative Site
  • Kraków, Poland, 31-531
    • Novartis Investigative Site
  • Lódz, Poland, 90-549
    • Novartis Investigative Site
  • Warszawa, Poland, 04-628
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08025
    • Novartis Investigative Site
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Andalucia
    • Malaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
  • Asturias
    • Oviedo, Asturias, Spain, 33006
      • Novartis Investigative Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Novartis Investigative Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Cataluña, Spain, 08003
      • Novartis Investigative Site
    • Hospitalet de Llobregat, Cataluña, Spain, 08907
      • Novartis Investigative Site
  • Galicia
    • Santiago de Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
    • Vigo, Galicia, Spain, 36200
      • Novartis Investigative Site
  • Madrid
    • Majadanonda, Madrid, Spain, 28220
      • Novartis Investigative Site
  • Pais Vasco
    • Galdakano, Pais Vasco, Spain, 48960
      • Novartis Investigative Site
• United States
  • Alabama
    • Mobile, Alabama, United States, 36693
      • Novartis Investigative Site
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Novartis Investigative Site
    • Tucson, Arizona, United States, 85723-0001
      • Novartis Investigative Site
    • Tucson, Arizona, United States, 85745
      • Novartis Investigative Site
  • California
    • Los Angeles, California, United States, 90033
      • Novartis Investigative Site
    • Los Angeles, California, United States, 90095
      • Novartis Investigative Site
    • San Diego, California, United States, 92161
      • Novartis Investigative Site
    • Stockton, California, United States, 95204
      • Novartis Investigative Site
    • Torrance, California, United States, 90502
      • Novartis Investigative Site
  • Colorado
    • Boulder, Colorado, United States, 80304
      • Novartis Investigative Site
  • Connecticut
    • Farmington, Connecticut, United States, 06030-3100
      • Novartis Investigative Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Novartis Investigative Site
    • Washington, District of Columbia, United States, 20037
      • Novartis Investigative Site
  • Florida
    • Gainesville, Florida, United States, 32610
      • Novartis Investigative Site
    • Hudson, Florida, United States, 34667
      • Novartis Investigative Site
    • Miami, Florida, United States, 33137-3732
      • Novartis Investigative Site
    • Port Charlotte, Florida, United States, 33952
      • Novartis Investigative Site
    • Safety Harbor, Florida, United States, 34695
      • Novartis Investigative Site
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Novartis Investigative Site
  • Indiana
    • Elkhart, Indiana, United States, 46514
      • Novartis Investigative Site
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Novartis Investigative Site
    • Louisville, Kentucky, United States, 40202
      • Novartis Investigative Site
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Novartis Investigative Site
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Novartis Investigative Site
  • Massachusetts
    • Boston, Massachusetts, United States
      • Novartis Investigative Site
  • Michigan
    • Flint, Michigan, United States, 48532
      • Novartis Investigative Site
    • Kalamazoo, Michigan, United States, 49048
      • Novartis Investigative Site
    • Midland, Michigan, United States, 48640
      • Novartis Investigative Site
    • Petoskey, Michigan, United States, 49770
      • Novartis Investigative Site
    • Saginaw, Michigan, United States, 48601
      • Novartis Investigative Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Novartis Investigative Site
    • St. Paul, Minnesota, United States, 55102
      • Novartis Investigative Site
  • Missouri
    • Columbia, Missouri, United States, 65212
      • Novartis Investigative Site
  • New Jersey
    • Ridgewood, New Jersey, United States, 07450
      • Novartis Investigative Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-5271
      • Novartis Investigative Site
  • New York
    • Buffalo, New York, United States, 14215
      • Novartis Investigative Site
    • New York, New York, United States, 10011
      • Novartis Investigative Site
    • Syracuse, New York, United States, 13210-1640
      • Novartis Investigative Site
    • Williamsville, New York, United States, 14221
      • Novartis Investigative Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27610
      • Novartis Investigative Site
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Novartis Investigative Site
  • Ohio
    • Cleveland, Ohio, United States, 44109-1998
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73109
      • Novartis Investigative Site
    • Tulsa, Oklahoma, United States, 74104-4243
      • Novartis Investigative Site
  • Oregon
    • Bend, Oregon, United States, 97701
      • Novartis Investigative Site
    • Hillsboro, Oregon, United States, 97123
      • Novartis Investigative Site
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822-2001
      • Novartis Investigative Site
    • Pittsburgh, Pennsylvania, United States, 15213
      • Novartis Investigative Site
  • Tennessee
    • Johnson City, Tennessee, United States, 37604
      • Novartis Investigative Site
    • Memphis, Tennessee, United States, 38104
      • Novartis Investigative Site
    • Oak Ridge, Tennessee, United States, 37830
      • Novartis Investigative Site
  • Texas
    • Dallas, Texas, United States, 75226
      • Novartis Investigative Site
    • Katy, Texas, United States, 77493
      • Novartis Investigative Site
    • San Antonio, Texas, United States, 78229-3900
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with CAD who have blood pressure in the pre-hypertensive range defined as a msSBP ≥ 125 and ≤ 139mmHg and a msDBP < 90mmHg.
• Patients with or without current treatment for hypertension
• Angiographic evidence of coronary artery disease
• At least 2 qualifying Cardiovascular risk factors at Visit 1

Exclusion Criteria:

• Baseline IVUS determined unacceptable
• Patients requiring treatment with disallowed study medications
• Patients with clinically significant heart disease
• Previous or current diagnosis of heart failure (NYHA Class IV) or a documented left ventricular ejection fraction of < 25%

• Patients requiring treatment with any 2 of the following classes of medication at Visit 1 or Visit 2:

  • Angiotensin converting enzyme inhibitors
  • Angiotensin receptor blockers
  • aldosterone receptor blockers or a direct renin inhibitor.
• Other conditions may apply

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
Placebo Comparator: 1	Drug: Placebo; Placebo
Experimental: 2; Aliskiren 300 mg	Drug: Aliskiren; 300 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Percent Atheroma Volume(PAV) After 104 Weeks of Treatment	Change from baseline in PAV for all matched slices of anatomically comparable segments of the target coronary artery were assessed by intravascular ultrasound (IVUS) evaluation after 104 weeks of treatment . calculation for change is the value at the later time point minus the value at the earlier time point, with positive numbers to represent increases and negative numbers to represent decreases	Baseline, 104 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Normalized Total Atheroma Volume (TAV) as Assessed by IVUS	Change from baseline in normalized total atheroma volume (TAV) (mm^3) for all matched slices of anatomically comparable segments of the target coronary artery were assess by IVUS after 104 weeks of treatment. calculation for change is the value at the later time point minus the value at the earlier time point, with positive numbers to represent increases and negative numbers to represent decreases	Baseline, 104 weeks
Patients That Demonstrated Evidence of Atheroma Regression	Atheroma regression is defined as change from baseline to endpoint in PAV <0 .	Baseline to endpoint (104 weeks)
Number of Patients With Adverse Events, Serious Adverse Events, and Death	overall safety and tolerability of aliskiren 300 mg compared to placebo in patients with CAD and BP in the pre-hypertensive (high normal) range with or without treatment for hypertension following 104 weeks of treatment. Any Adverse Event was defined as occurrence of any symptom regardless of intensity grade, Serious Adverse Event (SAEs) assessed as medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in persistent or significant disability/incapacity.	104 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Collaborators: The Cleveland Clinic

Publications and helpful links

General Publications

• Puri R, Nissen SE, Menon V, Shao M, Hsu A, Bakris GL, Kastelein JJ, Williams B, Armbrecht J, Brunel P, Kataoka Y, Nicholls SJ. Effects of aliskiren in diabetic and non-diabetic patients with coronary artery disease: Insights from AQUARIUS. Atherosclerosis. 2015 Dec;243(2):553-9. doi: 10.1016/j.atherosclerosis.2015.10.019. Epub 2015 Oct 20.
• Nicholls SJ, Bakris GL, Kastelein JJ, Menon V, Williams B, Armbrecht J, Brunel P, Nicolaides M, Hsu A, Hu B, Fang H, Puri R, Uno K, Kataoka Y, Bash D, Nissen SE. Effect of aliskiren on progression of coronary disease in patients with prehypertension: the AQUARIUS randomized clinical trial. JAMA. 2013 Sep 18;310(11):1135-44. doi: 10.1001/jama.2013.277169.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: February 26, 2009
• First Submitted That Met QC Criteria: February 27, 2009
• First Posted (Estimate): March 2, 2009

Study Record Updates

• Last Update Posted (Estimate): June 3, 2014
• Last Update Submitted That Met QC Criteria: May 20, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: coronary artery disease; IVUS; intravascular ultrasound; CAD; coronary angiography; coronary atherosclerosis; plasma renin activity; renin angiotensin aldosterone system,; direct renin inhibitors; coronary atheroma
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Atherosclerosis
• Other Study ID Numbers: CSPP100A2366; 2008-006447-40