Acetazolamide and Spironolactone to Increase Natriuresis in Congestive Heart Failure

Condition(s) targeted: Heart Failure

Intervention: Combination therapy with acetazolamide and low-dose loop diuretics (Drug); High-dose loop diuretics (Drug); Upfront therapy with oral spironolactone (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Hasselt University

Official(s) and/or principal investigator(s):
Wilfried Mullens, M.D. Ph.D., Principal Investigator, Affiliation: Ziekenhuis Oost-Limburg
Frederik H. Verbrugge, M.D. Ph.D., Principal Investigator, Affiliation: Ziekenhuis Oost-Limburg

Overall contact:
Frederik H. Verbrugge, M.D. Ph.D., Phone: +32473924199, Email: frederik.verbrugge@zol.be

This study has two primary objectives: 1. To compare combination therapy with acetazolamide and low-dose loop diuretics versus high-dose loop diuretics (standard of care) in patients with acute decompensated heart failure at high risk for diuretic resistance. 2. To demonstrate the safety and efficacy of upfront therapy with spironolactone in addition to loop diuretic therapy in patients with acute decompensated heart failure at high risk for diuretic resistance.

Official title: Diamox/Aldactone to Increase the URinary Excretion of Sodium: an Investigational Study in Congestive Heart Failure

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Acetazolamide arm: natriuresis 24 h

Spironolactone arm: incidence of hypo- (serum potassium <3.5 mmol/L) or hyperkalemia (serum potassium >5.0 mmol/L)

Secondary outcome:

NT-proBNP change after 72 h

Worsening renal function

Persistent renal impairment

Peak plasma aldosterone concentration after 72 h

Peak plasma renin activity after 72 h

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Older than 18 years and able to give informed consent

- Clinical diagnosis of acute decompensated heart failure within the previous 8 h

- At least two clinical signs of congestion (edema, ascites, jugular venous distension,

or pulmonary vascular congestion on chest radiography)

- Maintenance therapy with oral loop diuretics at a dose of at least 1 mg bumetanide (1

mg bumetanide = 40 mg furosemide = 20 mg torsemide) for at least 1 month before hospital admission

- NT-proBNP >1000 ng/L

- Left ventricular ejection fraction <50%

- At least one out of three of the following criteria:

- Serum sodium <136 mmol/L

- Serum urea/creatinine ratio >50 (comparable to a BUN/creatinine ratio >25)

- Admission serum creatinine increased with >0. 3 mg/dL compared to previous value

within 3 months before admission Exclusion Criteria:

- History of cardiac transplantation and/or ventricular assist device

- Concurrent diagnosis of an acute coronary syndrome defined as typical chest pain

and/or electrocardiographic changes in addition to a troponin rise >99th percentile

- Mean arterial blood pressure <65 mmHg, or systolic blood pressure <90 mmHg at the

moment of admission

- Use of intravenous inotropes, vasopressors or nitroprusside at any time point during

the study

- A baseline estimated glomerular filtration rate <15 mL/min/1. 73m² according to the

Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula at the moment of inclusion

- Use of renal replacement therapy or ultrafiltration before study inclusion

- Treatment with acetazolamide within the previous month

- Treatment with ≥2 mg bumetanide or an equivalent dose during the index

hospitalization before randomization

- Use of diuretics, vasopressin antagonists or mineralocorticoid receptor antagonist

not specified by the protocol

- Exposure to nephrotoxic agents (i. e. contrast dye) anticipated within 3 days

Frederik H. Verbrugge, M.D. Ph.D., Phone: +32473924199, Email: frederik.verbrugge@zol.be

Ziekenhuis Oost-Limburg, Genk, Limburg 3600, Belgium; Recruiting
Pieter Martens, M.D., Phone: +3289321516, Email: pieter_martens@icloud.com
Petra Nijst, M.D., Phone: +3289321525, Email: petra.nijst@zol.be
Frederik H. Verbrugge, M.D. Ph.D., Principal Investigator
Wilfried Mullens, M.D. Ph.D., Principal Investigator
Petra Nijst, M.D., Sub-Investigator
Philippe B. Bertrand, M.D. M.Sc., Sub-Investigator
Lars Grieten, Ph.D. M.Sc., Sub-Investigator
Matthias Dupont, M.D., Sub-Investigator
Joris Penders, M.D. Ph.D., Sub-Investigator
Pieter Martens, M.D., Sub-Investigator

University Hospital Leuven, Leuven, Vlaams-Brabant 3000, Belgium; Not yet recruiting
Walter Droogné, M.D., Phone: +3216343487, Email: walter.droogne@uzleuven.be
Anne Strijckmans, R.N., Phone: +3216343487, Email: anne.strijckmans@uzleuven.be

Starting date: November 2013
Last updated: August 2, 2015