ARIANA-CHF-RD: Safety and Efficacy Study of Add On Aliskiren in Patients With Heart Failure and Renal Impairment

Sponsor

University Medical Center Groningen (Other)

Overall Status

Terminated

CT.gov ID

NCT00881439

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purpose of this study is to examine the effect of add-on therapy with the direct renin inhibitor Aliskiren in comparison to placebo on renal blood flow in patients with heart failure and reduced renal function.

Primary outcome measure: change in renal blood flow at 6 months
Secondary outcome measures: changes in renal function, N-terminal pro Brain natriuretic peptide, left ventricular function, blood pressure and neurohormones

Condition or Disease	Intervention/Treatment	Phase
Heart Failure Kidney Failure	Drug: Aliskiren Drug: Placebo	Phase 2

Detailed Description

This study is a randomized, double-blind, placebo controlled, parallel group comparison trial, enrolling 100 patients (67 vs. 33) with stable CHF. Patients will be randomized to Aliskiren 300 mg once daily or corresponding Placebo for a period of 6 months. Efficacy measures will be performed at baseline and at the end of the study. Primary efficacy outcome is change in renal blood flow as measured by 131I-Hippuran clearance. Secondary outcome include change in renal function, neurohormones, left ventricular function and blood pressure. Safety assessments include renal function, changes in electrolytes, and blood pressure. Patients will be uptitrated to maximum tolerated doses of Aliskiren, and safety visits are planned 1 week after initiation and on a 2 month interval afterwards. A total of 8 visits are planned during the entire study period.

Study Design

Study Type:

Interventional

Actual Enrollment :

41 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Double-blind, Placebo-controlled, Randomized Trial Investigating the Safety and Efficacy of Additive Renin Inhibition With Aliskiren on Renal Blood Flow and Neurohormonal Activation in Patients With Chronic Heart Failure and Renal Dysfunction

Study Start Date :

Apr 1, 2009

Actual Primary Completion Date :

Jul 1, 2012

Actual Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo Matching Placebo once daily, 6 months
Active Comparator: Aliskiren	Drug: Aliskiren Oral, 300 mg, once daily, 6 months Other Names: Rasilez SPP100

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Drug: Placebo

Matching Placebo once daily, 6 months

Active Comparator: Aliskiren

Drug: Aliskiren

Oral, 300 mg, once daily, 6 months

Other Names:

Rasilez

SPP100

Outcome Measures

Primary Outcome Measures

Change in renal blood flow as assessed by 131I-Hippuran clearance [6 months]

Secondary Outcome Measures

change in glomerular filtration rate (GFR) as assessed by 125I-Iothalamate [6 months]
Change in systolic and diastolic blood pressure [6 months]
change in N-terminal pro brain natriuretic peptide levels (NT-proBNP) [6 months]
Change in left ventricular ejection fraction [6 months]
change in NYHA class, change in filtration fraction, change in albumin excretion, change in tubular function parameters, change in neurohormonal activation [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

NYHA II-IV Heart Failure
Left ventricular ejection fraction < 45%
Stable heart failure medication
eGFR by sMDRD formula between 30 and 60 mL/min/1.73m2

Exclusion Criteria:

Known hypersensitivity to study drug or ACEi
Concomitant treatment with both ARB and Aldosterone Receptor Antagonist
Symptomatic Hypotension
Acute Heart Failure
History of stroke, acute coronary syndrome, PCI or angioplasty within past 3 months
Serum potassium > 5.2 mmol/L
Right heart failure due to severe pulmonary disease
Other protocol-defined inclusion/exclusion criteria may apply