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 - ARIANA-CHF-RD
- Conditions
- Patients with chronic heart failure and reduced glomerular filtration rate.MedDRA version: 9.1Level: HLTClassification code 10038443Term: Renal failure and impairmentMedDRA version: 9.1Level: LLTClassification code 10008908Term: Chronic heart failure
- Registration Number
- EUCTR2008-007881-45-NL
- Lead Sponsor
- niversity Medical Center Groningen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- Not specified
•Out patients = 18 years of age, male or female.
•Patients with a diagnosis of chronic heart failure (NYHA Class II – IV)
•LVEF = 45% at visit 1 (local measurement, measured within the past 6 months assessed by echocardiogram, MUGA or ventricular angiography)
•Estimated GFR between 30 and 60 ml/min/1.73m2 as measured by the MDRD formula
•Patients must be treated with an ACE inhibitor at a stable dose (enalapril 10 mg daily at least or any other ACE inhibitor, e.g. ramipril, quinapril, lisinopril, fosinopril, perindopril, trandolapril; on equivalent doses, or maximum tolerated dose) or if intolerant to ACE inhibitors with ARB therapy (Candesartan 32 mg daily or any other ARB in equivalent dose, or maximum tolerated dose) for at least 4 weeks prior to visit 1.
•Patients must be treated with a beta blocker unless contraindicated or not tolerated at a stable dose for at least 4 weeks prior to visit 1 (for patients not on target dose or in absence of that medication, the reason should be documented).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
•History of hypersensitivity to any of the study drugs including history or allergy to ACEi’s as well as known or suspected contraindications to the study drugs or previous history of intolerance to high doses of ACEi’s during up titration process.
•Patients treated concomitantly with both ARB and aldosterone antagonist.
•Current acute decompensated heart failure (HF).
•Symptomatic hypotension and/ or less than 90 mmHg SBP at randomisation
•Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or major vascular surgery, percutaneous coronary intervention (PCI) or carotid angioplasty, within the past 3 months.
•Coronary or carotid artery disease likely to require surgical or PCI.
•Right heart failure due to severe pulmonary disease.
•Diagnosis of peripartum or chemotherapy induced cardiomyopathy within the last year.
•Patients with a history of heart transplant or who are on a transplant list or with LVAD device (left ventricular assistance device).
•Documented ventricular arrhythmia with syncopal episodes within past 3 months that is untreated.
•Documented history of ventricular tachycardia or ventricular fibrillation without ICD.
•Symptomatic bradycardia, or second or third degree heart block without a pacemaker.
•Implantation of a CRT (cardiac resynchronization therapy) device within prior 3 months.
•Presence of hemodynamically significant mitral and /or aortic valve disease, except mitral regurgitation secondary to left ventricular dilatation.
•Presence of hemodynamically significant obstructive lesions of left ventricular outflow tract, including aortic stenosis.
•Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs including, but not limited to, any of the following:
•Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury as indicated by abnormal lipase or amylase.
•Primary liver disease considered to be life threatening.
•Currently active gastritis, duodenal or gastric ulcers, or gastrointestinal/rectal bleeding during the 3 months prior to Visit 1.
•Serum potassium = 5.2 mEq/L at randomisation visit.
•History or presence of any other diseases (i.e. including malignancies) with a life expectancy of < 5 years.
•Current double-blind treatment in HF trials.
•Participation in an investigational drug study at the time of enrollment or within the past 30 days or 5 half lives of enrollment whichever is longer.
•Any surgical or medical condition that in the opinion of the investigator or medical monitor would jeopardize the evaluation of efficacy or safety.
•History of noncompliance to medical regimens and patients who are considered potentially unreliable.
•Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive Human Chorionic Gonadotropin (hCG) laboratory test (> 5 mIU/ml).
•Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum Follicle Stimulating Hormone (
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method