Effects of Aliskiren, Ramipril, and the Combination on Levels of Angiotensin II in Patients With Decompensated Systolic Heart Failure (ESCAPE-SHF)

Novartis

Status and phase: Completed; Phase 2

Conditions: Heart Failure

Treatments: Drug: Placebo to aliskiren; Drug: Placebo to ramipril; Drug: aliskiren; Drug: ramipril

Study type: Interventional

Funder types: Industry

Identifiers

NCT00923156

EudraCT 2008-001035-35

CSPP100A2252

Details and patient eligibility

About

In addition to the blood pressure lowering effects of aliskiren, it may have beneficial effects on blocking the so called RAAS (renin-angiotensin-aldosterone system) at the tissue level. An increase of angiotensin II is associated with progression of heart failure. Although the use of ACE-inhibitors in heart failure shows clinical benefit, an increase in angiotensin II due to an angiotensin II "escape" phenomenon is not desirable. It is not yet known if a direct renin inhibitor can reduce or even prevent the angiotensin II escape phenomenon associated with the use of an ACE-inhibitor. Therefore the study tested the effects of ramipril, aliskiren and the combination of both on levels of angiotensin II in the blood in patients with systolic heart failure

Enrollment: 123 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Decompensated systolic heart failure, left ventricular ejection fraction ≤40%
• Brain natriuretic peptide (BNP) level ≥ 100 pg/mL

Exclusion criteria

• Use of Angiotensin Converting Enzyme(ACE) or Angiotensin Receptor Blocker (ARB) inhibitor treatment following the run-in period or requirement of both treatments
• Acute heart failure secondary to acute myocardial infarction, acute coronary syndrome or new tachyarrhythmia
• Occurrence of unstable angina or myocardial infarction within 12 weeks prior to screening
• History of cardiomyopathy such as postpartum, restrictive, infective, hypertrophic obstructive
• History of right heart failure due to pulmonary disease
• History of untreated second or third degree atrioventricular heart block

Other protocol-defined inclusion/exclusion criteria applied

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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123 participants in 3 patient groups

Aliskiren

Experimental group

Description:

In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received aliskiren (150 mg once daily) up titrated to 300 mg once daily after 1 week of treatment following a clinical safety patient assessment at the study site and matching placebo of ramipril capsules.

Treatment:

Drug: Placebo to ramipril

Drug: ramipril

Drug: aliskiren

Ramipril

Experimental group

Description:

In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (Period 2), patients received ramipril 10 mg capsule o.d and matching placebo of aliskiren tablet.

Treatment:

Drug: Placebo to aliskiren

Drug: ramipril

Aliskiren plus Ramipril

Experimental group

Description:

In open label run-in phase (period 1), patients started with ramipril 2.5 mg or 5.0 mg capsule once daily (o.d) depending on previous treatment with RAAS blockers and up-titrated to ramipril 10 mg capsule o.d by end of period 1. In double blind phase (period 2), patients received ramipril (10 mg once daily capsule) and aliskiren (150 mg once daily tablet) up titrated to 300 mg once daily after 1 week of treatment following a clinical safety patient assessment at the study site

Treatment:

Drug: ramipril

Drug: aliskiren