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

Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00631917
• Other study ID #: CSPP100A2404
• Status: Completed
• Phase: Phase 4
• First received: March 3, 2008
• Last updated: June 30, 2011
• Start date: February 2008
• Est. completion date: September 2009

Study information

• Verified date: June 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 774
• Est. completion date: September 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Aliskiren
Aliskiren 300 mg once a day
• Ramipril
Ramipril 10 mg once a day

Other:
• Placebo to Ramipril
Placebo capsules to match ramipril.
• Placebo to Aliskiren
Placebo tablets to match aliskiren.

Locations

Country	Name	City	State
Argentina	Investigative Site	Investigative Site
Colombia	Investigative Site	Investigative Site
France	Investigative Site	Investigative Site
Germany	Investigative Site	Investigative Site
India	Investigative Site	investigative Site
Spain	Investigative Site	Investigative Site
United States	Investigative Site	Kansas City	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

United States,  Argentina,  Colombia,  France,  Germany,  India,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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)	No