protocolSection identificationModule nctId: NCT06273397, orgStudyIdInfo id: ACME-AHF, briefTitle: Acetazolamide or Metolazone in Acute Heart Failure, acronym: ACME-AHF, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-05-01, primaryCompletionDateStruct date: 2027-03-01, completionDateStruct date: 2027-05-01, studyFirstPostDateStruct date: 2024-02-22, lastUpdatePostDateStruct date: 2024-03-18, sponsorCollaboratorsModule leadSponsor name: Clinica Alemana de Santiago, class: OTHER, descriptionModule briefSummary: Impact of Acute Heart Failure:According to the World Health Organization (WHO), approximately 26 million people suffer from Heart Failure (HF), with a mortality rate of up to 50% within five years of diagnosis. Acute Heart Failure (AHF) exacerbations, leading to hospitalization, are common and represent the primary cause of hospital admissions in those over 65. Effective decongestion during hospitalization is crucial, as failure to achieve it doubles the risk of rehospitalization and mortality, incurring significant healthcare costs.Use of Diuretics in Acute Heart Failure:Diuretics, particularly loop diuretics like furosemide, are a cornerstone in managing AHF by inducing natriuresis and achieving decongestion. Clinical experience supports their use, though limited clinical trials exist. Pharmacological concepts guide their administration, emphasizing intravenous delivery in high doses and adjusting subsequent doses based on decongestive efficacy. Additionally, sequential tubular blockade with other diuretics like metolazone and acetazolamide is explored to enhance decongestion.Use of Metolazone and Acetazolamide:Sequential tubular blockade, using metolazone and acetazolamide in conjunction with furosemide, aims to achieve rapid and effective decongestion. While metolazone targets the distal tubule, inhibiting sodium-chloride channels, acetazolamide affects proximal tubular function. Studies like ADVOR (acetazolamide) and CLOROTIC (thiazide-like diuretic) demonstrate the potential benefits of combining these diuretics for quicker decongestion but with potential risks (in the case of Hydrochlorothiazide).Outcomes Measured by Major Studies:Recent studies assessing decongestion in AHF reveal a lack of uniformity in outcome selection. The primary focus should be on reducing rehospitalizations and post-discharge mortality by achieving effective decongestion. The ADVOR study, using a simple congestion score based on clinical and imaging criteria, underscores the importance of reaching a congestion score of 0 or 1 promptly.Congestion Monitoring:Monitoring diuretic treatment solely based on clinical aspects may not capture subclinical congestion, necessitating biochemical and imaging parameters. The ACME-AHF trial proposes a diagnostic score integrating clinical and imaging aspects to evaluate congestion status. Secondary outcomes include cumulative diuresis, weight loss, diuretic efficiency, and natriuresis, with a focus on natriuresis as a reliable physiological parameter for decongestion.Aim of the study:The ACME-AHF trial is designed to compare the efficacy and safety of two diuretic combination strategies: acetazolamide with furosemide and metolazone with furosemide. The primary objective is to relieve congestion, assessed using a congestion score, within the first three days of treatment during an hospitalization for acute heart failure., conditionsModule conditions: Heart Failure Acute, conditions: Decompensated Heart Failure, designModule studyType: INTERVENTIONAL, phases: NA, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, interventionModelDescription: This is an Open, Multicenter, Prospective, and Randomized study with three treatment arms. The outcomes to be assessed in the initial phase will be at 4 days post-randomization, followed by evaluation at 90 days after hospital discharge., primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 1050, type: ESTIMATED, armsInterventionsModule interventions name: Acetazolamide 250 MG, interventions name: Metolazone 2.5 MG, interventions name: Furosemide Injection, outcomesModule primaryOutcomes measure: Treatment success, secondaryOutcomes measure: Mortality, secondaryOutcomes measure: Worsening Heart Failure, secondaryOutcomes measure: Cumulative 24-hour Natriuresis, secondaryOutcomes measure: Cumulative weight loss, secondaryOutcomes measure: Subclinical congestion, secondaryOutcomes measure: Change in Hematocrit value, secondaryOutcomes measure: Change in NT-proBNP concentration, secondaryOutcomes measure: Change in CA125 value, otherOutcomes measure: Any adverse event, otherOutcomes measure: Changes in pH value, otherOutcomes measure: Change in plasma electrolyte values, eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule, hasResults: False