EFFECT OF LOOP DIURETIC COMBINATION THERAPY WITH CARBONIC ANHYDRASE INHIBITOR IN PATIENTS WITH ACUTELY DECOMPENSATED HEART FAILURE AND ACUTE KIDNEY INJURY: A CONTROLLED CLINICAL TRIAL AND RANDOMIZED

• Grant number: 25/01828-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: March 31, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Caroline Ferreira da Silva Mazeto Pupo da Silveira
• Grantee: Diego Henrique de Sousa
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Introduction: Acutely decompensated heart failure (CDI) is the main cause ofhospitalization among patients aged 65 and over, with acute kidney injury (AKI)being a frequent complication in these individuals. Treatment of CDI often involvesthe use of loop diuretics, but chronic administration of these agents can lead to thedevelopment of resistance, presenting a significant clinical challenge. In this context,the addition of diuretics from other classes, such as thiazides or acetazolamide, is astrategy used to promote a sequential blockade in the nephron. However, evaluationof the efficacy of this combined approach in decompensated heart failure associatedwith acute kidney injury is still limited. The aim of this study is to investigate theimpact of adding acetazolamide to intravenous diuretic therapy in patients with CDIwho present clinical signs of volume overload and AKI. Objective: To analyze theeffect of adding acetazolamide to intravenous loop diuretic therapy in CDI patientswith clinical signs of volume overload and AKI. Method: This is a clinical trial,controlled, randomized, non-blind, and single-center study. Patients with acutedecompensated heart failure, clinical signs of volume overload (such as edema,ascites, pleural effusion or pulmonary congestion) and KDIGO 1 and 2 ARF will beincluded in the study. Non-inclusion criteria will be: use of vasoactive drugs, systolicblood pressure <90 mmHg, chronic kidney disease stage 5 or AKI KDIGO 3 onadmission, presence of hemodynamically significant arrhythmias, hypokalemia andhyponatremia on admission with values equal to or less than 2, 5 or 125 mmoL/L,respectively (or any symptomatic sodium value), inability to comply with plannedstudy procedures, or refusal to participate. Patients will be randomized into threegroups to receive one of the following interventions: bolus intravenous loop diuretics,bolus intravenous loop diuretics associated with acetazolamide and bolusintravenous loop diuretics together with hydrochlorothiazide. The primary outcomewill be clinical improvement in signs of congestion, changes in body weight andchanges in patient-reported dyspnea at 72 hours after randomization. Secondaryoutcomes will be: length of hospital stay, rehospitalization for heart failure,assessment of AKI progression to KDIGO 3 and all-cause mortality during 3 monthsof follow-up.