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A Study Evaluating the Gastrointestinal (GI) Safety and Tolerability of Aliskiren Compared to Ramipril in Essential Hypertension

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00631917
First received: March 3, 2008
Last updated: June 30, 2011
Last verified: June 2011
  Purpose

This study will evaluate the long-term gastrointestinal (GI) safety and efficacy of aliskiren (300 mg) compared to ramipril (10mg) in patients ≥ 50 years with essential hypertension.


Condition Intervention Phase
Hypertension
Drug: Aliskiren
Drug: Ramipril
Other: Placebo to Ramipril
Other: Placebo to Aliskiren
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 54 Week, Randomized, Double-blind, Parallel-group, Multicenter Study Evaluating the Long-term Gastrointestinal (GI) Safety and Tolerability of Aliskiren (300 mg) Compared to Ramipril (10 mg) in Patients With Essential Hypertension

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percentage of Participants With Colonic Pathology [ Time Frame: 54 weeks ] [ Designated as safety issue: Yes ]
    The primary analysis variable was the occurrence of an abnormal colonoscopy finding (defined as hyper-plastic polyps, inflammatory polyps, adenomatous polyps or carcinoma) at or prior to the planned one year visit. The occurrence of colonic pathology was identified during colonoscopy and histopathologic examination of biopsy. The composite endpoint was evaluated after one year of treatment with an aliskiren-based regimen compared to a ramipril-based regimen.

  • Summary of the End of Study Colonoscopy Results [ Time Frame: 54 weeks ] [ Designated as safety issue: Yes ]
    During each colonoscopy procedure, random biopsy samples were taken from normal appearing mucosa in both the cecum and rectum in addition to obvious endoscopically atypical areas. The mucosal biopsy samples were evaluated for mucosal hyperplasia, dysplasia, and inflammation. Anything noted as a distinct visual abnormality from cecum to rectum such as ulcers, erythematous mucosa, or polyps, was photographed and biopsied for histopathology evaluation. Colonic lesions were categorized according to location in the colon, size, number, and morphology.


Secondary Outcome Measures:
  • Percentage of Participants With Each of the Individual Components of Colonic Pathology [ Time Frame: 54 weeks ] [ Designated as safety issue: Yes ]
    Assessment of the occurrence of the individual components (hyperplastic polyps, inflammatory polyps, adenomatous polyps or carcinomas) of the composite endpoint (colonic pathology) following one-year of treatment with an aliskiren-based regimen compared to a ramipril-based regimen.

  • Mucosal Hyperplasia Score in Rectal and Cecal Mucosal Biopsy Specimens After One Year of Treatment [ Time Frame: 54 weeks ] [ Designated as safety issue: Yes ]
    Maximum hyperplasia score at end of study across rectal and cecal mucosa biopsy specimens. Score of 0 is no change from baseline, the minimum possible score. Score > 0 is worsening from baseline in which the maximum possible score is 3.

  • Percentage of Participants Achieving the Mean Sitting Blood Pressure Control Target [ Time Frame: Weeks 8, 30 and End of Study (54 weeks) ] [ Designated as safety issue: No ]
    The mean sitting blood pressure control target is defined as less than 140/90 mmHg (or 130/80 mmHg for diabetic patients)


Enrollment: 774
Study Start Date: February 2008
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aliskiren
For the first 2 weeks of the study, participants received aliskiren 150 mg once a day and were then forced titrated to aliskiren 300 mg once a day for 52 weeks. Participants also received a placebo capsule to match ramipril once a day for the study duration.
Drug: Aliskiren
Aliskiren 300 mg once a day
Other: Placebo to Ramipril
Placebo capsules to match ramipril.
Active Comparator: Ramipril
For the first 2 weeks of the study participants received 5 mg ramipril orally once a day and were then forced titrated to ramipril 10 mg once a day for 52 weeks. Participants also received placebo to aliskiren for the duration of the study.
Drug: Ramipril
Ramipril 10 mg once a day
Other: Placebo to Aliskiren
Placebo tablets to match aliskiren.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female outpatients, 50 years of age and older with a diagnosis of essential hypertension
  • Successful high quality colonoscopy at baseline including visualization of the entire colon and the cecum as confirmed by a photograph and collection of the rectal and cecal mucosal biopsy samples
  • All rectal, colon or cecal polyps found at baseline colonoscopy must be completely resected endoscopically at the time of the procedure.
  • Patients who are eligible and able to participate in the study, and who consent to do so after the purpose and nature of the investigation have been clearly explained to them (written informed consent).

Exclusion Criteria:

  • Previously treated in an aliskiren study.
  • Current evidence of inflammatory bowel disease, the presence of colonic ulcerations (or other indices of colitis of any type) or colorectal carcinoma including carcinoma in situ found at baseline colonoscopy.
  • History of gastrointestinal carcinoma, Crohn's disease, ulcerative colitis, microscopic colitis.
  • History of familial polyposis or hereditary nonpolyposis colorectal cancer.
  • History of confirmed diverticulitis within 12 months of Visit 1.
  • History of celiac disease (gluten intolerance).
  • History of or current evidence on the baseline colonoscopy of melanosis coli.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00631917

Locations
United States, Missouri
Investigative Site
Kansas City, Missouri, United States
Argentina
Investigative Site
Investigative Site, Argentina
Colombia
Investigative Site
Investigative Site, Colombia
France
Investigative Site
Investigative Site, France
Germany
Investigative Site
Investigative Site, Germany
India
Investigative Site
investigative Site, India
Spain
Investigative Site
Investigative Site, Spain
Sponsors and Collaborators
Novartis
Investigators
Study Chair: Novartis 862-778-8300
  More Information

No publications provided

Responsible Party: Study Director, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00631917     History of Changes
Other Study ID Numbers: CSPP100A2404
Study First Received: March 3, 2008
Results First Received: January 5, 2011
Last Updated: June 30, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Hypertension, aliskiren, ramipril, colonoscopy

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

ClinicalTrials.gov processed this record on November 25, 2014