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

Novartis

Status and phase: Terminated; Phase 4

Conditions: Hypertension With Metabolic Syndrome

Treatments: Drug: Amlodipine; Drug: Aliskiren; Drug: Ramipril

Study type: Interventional

Funder types: Industry

Identifiers

NCT00542269

CSPP100AGB01

Details and patient eligibility

About

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.

Enrollment: 178 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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).

Exclusion criteria

• 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.

Other protocol-defined inclusion/exclusion criteria applied to the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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178 participants in 3 patient groups

Aliskiren / ramipril / amlodipine

Experimental group

Description:

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.

Treatment:

Drug: Amlodipine

Drug: Ramipril

Drug: Aliskiren

Aliskiren / amlodipine

Experimental group

Description:

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.

Treatment:

Drug: Amlodipine

Drug: Aliskiren

Ramipril / amlodipine

Active Comparator group

Description:

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.

Treatment:

Drug: Amlodipine

Drug: Ramipril