A Study Evaluating the Gastrointestinal (GI) Safety and Tolerability of Aliskiren Compared to Ramipril in Essential Hypertension
- Conditions
- Hypertension
- Interventions
- Registration Number
- NCT00631917
- Lead Sponsor
- Novartis
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 774
- 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).
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ramipril Placebo to Aliskiren 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. Aliskiren 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. Aliskiren Placebo to Ramipril 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. Ramipril 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Colonic Pathology 54 weeks 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 54 weeks 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
Name Time Method Percentage of Participants With Each of the Individual Components of Colonic Pathology 54 weeks 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 54 weeks 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 Weeks 8, 30 and End of Study (54 weeks) The mean sitting blood pressure control target is defined as less than 140/90 mmHg (or 130/80 mmHg for diabetic patients)
Trial Locations
- Locations (1)
Investigative Site
🇪🇸Investigative Site, Spain