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

Primary Purpose

Hypertension

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Aliskiren
Ramipril
Placebo to Ramipril
Placebo to Aliskiren
Sponsored by
Novartis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypertension focused on measuring Hypertension, aliskiren, ramipril, colonoscopy

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site
  • Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Aliskiren

Ramipril

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Percentage of Participants With Colonic Pathology
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
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
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
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
The mean sitting blood pressure control target is defined as less than 140/90 mmHg (or 130/80 mmHg for diabetic patients)

Full Information

First Posted
March 3, 2008
Last Updated
June 30, 2011
Sponsor
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT00631917
Brief Title
A Study Evaluating the Gastrointestinal (GI) Safety and Tolerability of Aliskiren Compared to Ramipril in Essential Hypertension
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2011
Overall Recruitment Status
Completed
Study Start Date
February 2008 (undefined)
Primary Completion Date
September 2009 (Actual)
Study Completion Date
September 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Novartis

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension
Keywords
Hypertension, aliskiren, ramipril, colonoscopy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
774 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Aliskiren
Arm Type
Experimental
Arm Description
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.
Arm Title
Ramipril
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Aliskiren
Intervention Description
Aliskiren 300 mg once a day
Intervention Type
Drug
Intervention Name(s)
Ramipril
Intervention Description
Ramipril 10 mg once a day
Intervention Type
Other
Intervention Name(s)
Placebo to Ramipril
Intervention Description
Placebo capsules to match ramipril.
Intervention Type
Other
Intervention Name(s)
Placebo to Aliskiren
Intervention Description
Placebo tablets to match aliskiren.
Primary Outcome Measure Information:
Title
Percentage of Participants With Colonic Pathology
Description
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.
Time Frame
54 weeks
Title
Summary of the End of Study Colonoscopy Results
Description
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.
Time Frame
54 weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants With Each of the Individual Components of Colonic Pathology
Description
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.
Time Frame
54 weeks
Title
Mucosal Hyperplasia Score in Rectal and Cecal Mucosal Biopsy Specimens After One Year of Treatment
Description
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.
Time Frame
54 weeks
Title
Percentage of Participants Achieving the Mean Sitting Blood Pressure Control Target
Description
The mean sitting blood pressure control target is defined as less than 140/90 mmHg (or 130/80 mmHg for diabetic patients)
Time Frame
Weeks 8, 30 and End of Study (54 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis
Organizational Affiliation
862-778-8300
Official's Role
Study Chair
Facility Information:
Facility Name
Investigative Site
City
Kansas City
State/Province
Missouri
Country
United States
Facility Name
Investigative Site
City
Investigative Site
Country
Argentina
Facility Name
Investigative Site
City
Investigative Site
Country
Colombia
Facility Name
Investigative Site
City
Investigative Site
Country
France
Facility Name
Investigative Site
City
Investigative Site
Country
Germany
Facility Name
Investigative Site
City
investigative Site
Country
India
Facility Name
Investigative Site
City
Investigative Site
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
33089502
Citation
Wang GM, Li LJ, Tang WL, Wright JM. Renin inhibitors versus angiotensin converting enzyme (ACE) inhibitors for primary hypertension. Cochrane Database Syst Rev. 2020 Oct 22;10(10):CD012569. doi: 10.1002/14651858.CD012569.pub2.
Results Reference
derived

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

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