Safety and Efficacy Study of Add On Aliskiren in Patients With Heart Failure and Renal Impairment

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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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

Conditions
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Heart Failure, Kidney Failure

Intervention / Treatment
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* Drug: Aliskiren
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching Placebo once daily, 6 months<br>|
| Active Comparator: Aliskiren<br> | Drug: Aliskiren<br>* Oral, 300 mg, once daily, 6 months<br>* Other names: SPP100;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in renal blood flow as assessed by 131I-Hippuran clearance |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure, Renal Failure, Cardiorenal Syndrome, Renin inhibition, Aliskiren