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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Aliskiren
* Drug: Ramipril
* Other: Placebo to Ramipril
* Other: Placebo to Aliskiren


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aliskiren<br>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<br>* Aliskiren 300 mg once a day<br>Other: Placebo to Ramipril<br>* Placebo capsules to match ramipril.<br>|
| Active Comparator: Ramipril<br>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<br>* Ramipril 10 mg once a day<br>Other: Placebo to Aliskiren<br>* Placebo tablets to match aliskiren.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 54 weeks | 
| 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. | 54 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 54 weeks | 
| 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. | 54 weeks | 
| 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) | Weeks 8, 30 and End of Study (54 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, aliskiren, ramipril, colonoscopy