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

NCT00631917 | Completed Phase 4 Results

• 1 other identifier: CSPP100A2404
• Study Type: interventional
• Target: 774
• Locations: 7 countries
• Sites: 7

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.

Conditions

Hypertension

Keywords

Hypertension, aliskiren, ramipril, colonoscopy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Percentage of Participants With Each of the Individual Components of Colonic Pathology

  54 weeks

• Mucosal Hyperplasia Score in Rectal and Cecal Mucosal Biopsy Specimens After One Year of Treatment

  54 weeks

• Percentage of Participants Achieving the Mean Sitting Blood Pressure Control Target

  Weeks 8, 30 and End of Study (54 weeks)

Study Arms (2)

Aliskiren

EXPERIMENTAL

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; Other: Placebo to Ramipril

Ramipril

ACTIVE COMPARATOR

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; Other: Placebo to Aliskiren

Interventions

Aliskiren DRUG

Aliskiren 300 mg once a day

Aliskiren

Ramipril DRUG

Ramipril 10 mg once a day

Ramipril

Placebo to Ramipril OTHER

Placebo capsules to match ramipril.

Aliskiren

Placebo to Aliskiren OTHER

Placebo tablets to match aliskiren.

Ramipril

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis: lead

Study Sites (7)

Investigative Site

Kansas City, Missouri, United States

Location

Investigative Site

Investigative Site, Argentina

Location

Investigative Site

Investigative Site, Colombia, Colombia

Location

Investigative Site

Investigative Site, France

Location

Investigative Site

Investigative Site, Germany

Location

Investigative Site

Investigative Site, India

Location

Investigative Site

Investigative Site, Spain

Location

Related Publications (1)

• 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.

  PMID: 33089502 DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

aliskiren; Ramipril

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis

  862-778-8300

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 3, 2008
• First Posted: March 10, 2008
• Study Start: February 1, 2008
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: July 12, 2011
• Results First Posted: June 21, 2011

Record last verified: 2011-06

Locations

DE (1); IN (1); FR (1); US (1); AR (1); ES (1); CO (1)