Clinical trial NCT00881439: Safety and Efficacy Study of Add On Aliskiren in Patients With Heart Failure and Renal Impairment
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Heart Failure
Kidney Failure
Keywords: Heart failure
Renal Failure
Cardiorenal Syndrome
Renin inhibition
Aliskiren
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2009-04-15
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in renal blood flow as assessed by 131I-Hippuran clearance
timeFrame: 6 months
Secondary outcomes:
measure: change in glomerular filtration rate (GFR) as assessed by 125I-Iothalamate
timeFrame: 6 months
measure: Change in systolic and diastolic blood pressure
timeFrame: 6 months
measure: change in N-terminal pro brain natriuretic peptide levels (NT-proBNP)
timeFrame: 6 months
measure: Change in left ventricular ejection fraction
timeFrame: 6 months
measure: change in NYHA class, change in filtration fraction, change in albumin excretion, change in tubular function parameters, change in neurohormonal activation
timeFrame: 6 months
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
References:
citation: McMurray JJ, Pitt B, Latini R, Maggioni AP, Solomon SD, Keefe DL, Ford J, Verma A, Lewsey J; Aliskiren Observation of Heart Failure Treatment (ALOFT) Investigators. Effects of the oral direct renin inhibitor aliskiren in patients with symptomatic heart failure. Circ Heart Fail. 2008 May;1(1):17-24. doi: 10.1161/CIRCHEARTFAILURE.107.740704.
citation: Schroten NF, Damman K, Hemmelder MH, Voors AA, Navis G, Gaillard CA, van Veldhuisen DJ, Van Gilst WH, Hillege HL. Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction). Am Heart J. 2015 May;169(5):693-701.e3. doi: 10.1016/j.ahj.2014.12.016. Epub 2015 Jan 7.