Efficacy and Safety of Aliskiren/Ramipril/Amlodipine Compared With Ramipril/Amlodipine and Aliskiren/Amlodipine in Patients With Metabolic Syndrome

NCT00542269 | Terminated Phase 4 Results

• 1 other identifier: CSPP100AGB01
• Study Type: interventional
• Target: 178
• Locations: 1 country
• Sites: 1

Brief Summary

This proof of concept study is designed to evaluate the efficacy and safety of the combination therapy of aliskiren and ramipril as add-on to amlodipine in the treatment of patients with essential hypertension and metabolic syndrome who do not respond adequately to amlodipine monotherapy.

Conditions

Hypertension With Metabolic Syndrome

Keywords

Hypertension; Metabolic Syndrome; Dual combination therapy; Triple combination therapy; Aliskiren; Direct Renin inhibitor

Outcome Measures

Primary Outcomes (2)

• Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study - Aliskiren/Ramipril/Amlodipine vs Ramipril/Amlodipine)

  Automated blood pressure determinations were made with the Omron HEM-705CP blood pressure monitor at trough (24 hours ± 3 hours post-dose) and recorded at all study visits following detailed directions specified in the study protocol. Three readings were made and msSBP was calculated as the average of the 3 readings. In the event of aberrant readings, ie, the lowest reading was ≥ 10 mmHg systolic or ≥ 5 mmHg diastolic lower than the highest of the 3 readings, 3 additional readings were obtained. A negative change indicates improvement.

  Baseline to Week 12

• Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study - Aliskiren/Amlodipine vs Ramipril/Amlodipine

  Automated blood pressure determinations were made with the Omron HEM-705CP blood pressure monitor at trough (24 hours ± 3 hours post-dose) and recorded at all study visits following detailed directions specified in the study protocol. Three readings were made and msSBP was calculated as the average of the 3 readings. In the event of aberrant readings, ie, the lowest reading was ≥ 10 mmHg systolic or ≥ 5 mmHg diastolic lower than the highest of the 3 readings, 3 additional readings were obtained. A negative change indicates improvement.

  Baseline to Week 12

Secondary Outcomes (8)

• Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study - Aliskiren/Ramipril/Amlodipine vs Ramipril/Amlodipine

  Baseline to Week 12

• Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study - Aliskiren/Amlodipine vs Ramipril/Amlodipine

  Baseline to Week 12

• Percentage of Patients Who Achieved Normalized Blood Pressure at End of Study

  Week 12

• Change in HOMA-IR From Baseline to End of Study

  Baseline to Week 12

• Change in HOMA-β From Baseline to End of Study

  Baseline to Week 12

Study Arms (3)

Aliskiren / ramipril / amlodipine

EXPERIMENTAL

6 weeks treatment with aliskiren 150 mg tablets, ramipril 5 mg capsules, and amlodipine 5-10 mg tablets followed by an additional 6 weeks treatment with aliskiren 300 mg tablets, ramipril 10 mg capsules, and amlodipine 5-10 mg tablets. Patients received amlodipine 5 mg (or 10 mg if they were receiving 10 mg prior to study start). Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed.

Drug: Amlodipine; Drug: Aliskiren; Drug: Ramipril

Aliskiren / amlodipine

EXPERIMENTAL

6 weeks treatment with aliskiren 150 mg tablets, ramipril 5 mg placebo capsules, and amlodipine 5-10 mg tablets followed by an additional 6 weeks treatment with aliskiren 300 mg tablets, ramipril 10 mg placebo capsules, and amlodipine 5-10 mg tablets. Patients received amlodipine 5 mg (or 10 mg if they were receiving 10 mg prior to study start). Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed.

Drug: Amlodipine; Drug: Aliskiren

Ramipril / amlodipine

ACTIVE COMPARATOR

6 weeks treatment with aliskiren 150 mg placebo tablets, ramipril 5 mg capsules, and amlodipine 5-10 mg tablets followed by an additional 6 weeks treatment with aliskiren 300 mg placebo tablets, ramipril 10 mg capsules, and amlodipine 5-10 mg tablets. Patients received amlodipine 5 mg (or 10 mg if they were receiving 10 mg prior to study start). Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed.

Drug: Amlodipine; Drug: Ramipril

Interventions

Amlodipine DRUG

amlodipine 5-10 mg tablets. Patients received amlodipine 5 mg (or 10 mg if they were receiving 10 mg prior to study start). Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed.

Aliskiren / amlodipine; Aliskiren / ramipril / amlodipine; Ramipril / amlodipine

Aliskiren DRUG

aliskiren 150-300 mg tablets. Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed.

Aliskiren / amlodipine; Aliskiren / ramipril / amlodipine

Ramipril DRUG

ramipril 5-10 mg capsules. Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed.

Aliskiren / ramipril / amlodipine; Ramipril / amlodipine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Outpatients 18-75 years of age.
• Male or female patients are eligible.
• Patients with a diagnosis of hypertension:
• Newly diagnosed patients or patients who have not been treated for hypertension within the 4 weeks prior to Visit 1 must have a mean sitting systolic blood pressure (MSSBP) \> 150 mmHg and \< 180 mmHg at Visit 1.
• Patients treated with antihypertensive monotherapy must have a MSSBP ≥ 140 mmHg and \<180 mmHg at Visit 1.
• Patients taking amlodipine monotherapy MSSBP \> 140 mmHg and \< 180 mmHg at visit 1.
• All patients must have a MSSBP ≥ 140 mmHg and \< 180 mmHg at Visit 3, the end of the amlodipine run-in period.
• Metabolic syndrome.
• 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 has been clearly explained to them (written inform consent form).

You may not qualify if:

• Severe hypertension (office cuff MSDBP ≥ 115 mmHg and/or MSSBP ≥ 180 mmHg).
• History or evidence of a secondary form of hypertension.
• History of hypertensive encephalopathy or cerebrovascular accident, transient ischemic cerebral attack (TIA), myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI).
• Serum sodium \< 135 mmol/L at Visit 1 if confirmed on repeat sample.
• Serum potassium \< 3.5 mmol/L or ≥ 5.3 mmol/L at Visit 1, if confirmed on repeat sample.
• Type 1 diabetes mellitus.
• Type 2 diabetes if oral hypoglycaemic therapy changed (dose change or medication change) in previous 3 months.
• Pregnant or nursing (lactating) women.

Sponsors & Collaborators

• Novartis: lead

Study Sites (1)

Addenbrookes Hospital

Cambridge, United Kingdom

Location

MeSH Terms

Conditions

Hypertension; Metabolic Syndrome

Interventions

Amlodipine; aliskiren; Ramipril

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 778-8300

Study Officials

• Novartis

  Novartis Great Britian

  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: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 9, 2007
• First Posted: October 11, 2007
• Study Start: March 1, 2008
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: May 24, 2011
• Results First Posted: May 24, 2011

Record last verified: 2011-04

Locations

GB (1)