Patients with chronic heart failure and reduced glomerular filtration rate. MedDRA version: 9.1 Level: HLT Classification code 10038443 Term: Renal failure and impairment MedDRA version: 9.1 Level: LLT Classification code 10008908 Term: Chronic heart failure
Conditions
Interventions
Trade Name: Rasilez
Product Name: Aliskiren
Product Code: SPP100
Pharmaceutical Form: Tablet
CAS Number: 173334571
Other descriptive name: ALISKIREN
Concentration unit: mg milligram(s)
Concentration t
Sponsors
University Medical Center Groningen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 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
Exclusion criteria
Exclusion criteria: • 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 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 (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to test if add-on therapy with aliskiren improves RBF in patients with CHF (NYHA Class II - IV) and RD treated with renin-angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II type 1 receptor blockers (ARB).;Secondary Objective: Secondary objectives are to examine the effect of addition of aliskiren on RD expressed as glomerular filtration rate(GFR) as measured by clearance of 125I-Iothalamate, filtration fraction(FF) as measured by GFR/Effective Renal Plasma Flow, circulating plasma values of markers of renin-angiotensin (RAS) system activity, including plasma renin activity, angiotensin II, angiotensin converting enzyme activity and chymase activity, levels of N Terminal-proBrain Natriuretic Peptides, left ventricular ejection fraction as measured by radionucleotide ventriculography, urinary levels of markers of glomerular and tubular damage, including urinary albumin ecretion (UAE), N-acetyl-beta-D-glucosaminidase (NAG), neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1), NYHA Association class, Patient’s and Physician’s global assessment score’s and on heart rate, systolic and diastolic blood pressure.;Primary end point(s): Change in Renal Blood Flow from baseline to 26 weeks with additive renin-inhibition with aliskiren | — |
Countries
Netherlands
Outcome results
None listed