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

Heart Failure Clinical Trial

— ARIANA-CHF-RD  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00881439
• Other study ID #: ARIANA
• Status: Terminated
• Phase: Phase 2
• First received: April 14, 2009
• Last updated: May 16, 2013
• Start date: April 2009
• Est. completion date: December 2012

Study information

• Verified date: May 2013
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)Netherlands: Medicines Evaluation Board (MEB)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 41
• Est. completion date: December 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Failure
• Kidney Failure
• Renal Insufficiency

Intervention

Drug:
• Aliskiren
Oral, 300 mg, once daily, 6 months
• Placebo
Matching Placebo once daily, 6 months

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in renal blood flow as assessed by 131I-Hippuran clearance		6 months	No
Secondary	change in glomerular filtration rate (GFR) as assessed by 125I-Iothalamate		6 months	No
Secondary	Change in systolic and diastolic blood pressure		6 months	Yes
Secondary	change in N-terminal pro brain natriuretic peptide levels (NT-proBNP)		6 months	No
Secondary	Change in left ventricular ejection fraction		6 months	No
Secondary	change in NYHA class, change in filtration fraction, change in albumin excretion, change in tubular function parameters, change in neurohormonal activation		6 months	No