A multi-center, randomized, double-blind, phase IV clinical trial to investigate if therapy with Acetazolamide (Diamox®) improves diuretic efficacy in decompensated heart failure patients to allow for a better/faster decongestion.
- Conditions
- The study population will consist of patients hospitalized with decompensated heart failure and demonstrating at least one clinical sign of volume overload.MedDRA version: 20.0Level: LLTClassification code 10019284Term: Heart failure, congestiveSystem Organ Class: 100000004849Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2018-001345-14-BE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 519
- An elective or emergency hospital admission with clinical diagnosis of ADHF and at least one clinical sign of volume overload (e.g. oedema, ascites or pleural effusion)
- Maintenance therapy with oral loop diuretics at a dose of at least 1 mg bumetanide or 40 mg furosemide or 20 mg torsemide for at least 1 month before hospital admission
- Plasma NT proBNP levels >1000 ng/mL or BNP levels >250 ng/mL at screening
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 129
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 390
- Concurrent diagnosis of an acute coronary syndrome defined as typical chest pain in addition to a troponin rise above the 99th percentile and/or electrocardiographic changes suggestive of cardiac ischemia
- A previous or current diagnosis of hypertrophic, restrictive, or constrictive cardiomyopathy as documented in the medical record
- History of congenital heart disease requiring surgical correction
- History of cardiac transplantation and/or ventricular assist device
- Systolic blood pressure <90 mmHg or mean arterial pressure <65 mmHg at the moment of admission
- Expected use of intravenous inotropes, vasopressors or nitroprusside during the study. Use of nitrates is allowed only if the patient’s systolic blood pressure is >140 mmHg
- Estimated glomerular filtration rate (eGFR) <20 mL/min/1.73m² at screening
- Use of renal replacement therapy or ultrafiltration at any time before study inclusion
- Treatment with intravenous loop diuretics > 2 mg bumetanide during the index hospitalization before randomization
- Treatment with acetazolamide during the index hospitalization before randomization
- Exposure to nephrotoxic agents (i.e. contrast dye) anticipated within the next 3 days
- Use of any non-protocol defined diuretic agent with the exception of mineralocorticoid receptor antagonists. Thiazides, metolazone, indapamide and amiloride should be stopped upon study inclusion. If patient is taking a combination drug including a thiazide-type diuretic, the thiazide-type diuretic should be stopped upon study inclusion.
- Current use of sodium-glucose transporter 2 inhibitors
- Subjects who are pregnant or breastfeeding
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To investigate if combination therapy with acetazolamide improves loop diuretic efficacy to increase diuresis in decompensated heart failure (HF) patients, allowing for a better/faster decongestion and potentially resulting in improved clinical outcome and increased quality of life.;Secondary Objective: - Combined end-point of all-cause mortality and heart failure readmission during 3 months of follow-up<br>- Length of index hospital admission<br>- Longitudinal changes in EuroQoL five dimensions questionnaire (EQ-5D) (baseline, the morning of day 4, any readmission, and 3 months).<br>;Primary end point(s): Treatment success (decongestion achieved) on the morning of day 4 without the need for escalating diuretic strategy (doubling loop diuretic dose, addition of chlorthalidone, or ultrafiltration) on the morning of day 3 ;Timepoint(s) of evaluation of this end point: morning of study day 4
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Combined end-point of all-cause mortality and heart failure readmission during 3 months of follow-up<br>- Length of index hospital admission<br>- Longitudinal changes in EuroQoL five dimensions questionnaire (EQ-5D) (baseline, the morning of day 4, any readmission, and 3 months).<br>;Timepoint(s) of evaluation of this end point: day 4, hospital submission and 3 months after study start