Decompensated Heart Failure Clinical Trial
— ACME-AHFOfficial title:
Acetazolamide or Metolazone in Acute Heart Failure
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.
Status | Not yet recruiting |
Enrollment | 1050 |
Est. completion date | May 1, 2027 |
Est. primary completion date | March 1, 2027 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Acute heart failure: Hospitalization due to symptoms of heart failure, congestion signs documented with a congestion score greater than 1, NT-proBNP above 1000 pg/ml. - Randomization within 24 hours of admission. Exclusion Criteria: - Under 18 years of age. - Received more than one dose of intravenous furosemide before randomization. - Cause of heart failure: hypertrophic or restrictive cardiomyopathy, or constrictive pericarditis. - Acute coronary syndrome or severe acute valvulopathy as the cause of decompensation. - Systolic blood pressure < 90mmHg before randomization. - Requirement for vasopressors, inotropes, or invasive mechanical ventilation. Use of intravenous vasodilators or non-invasive mechanical ventilation is allowed. - Glomerular filtration rate < 20ml/min/1.73m2. - Potassium < 2.5 mEQ/L or Sodium < 125 mEQ/L before randomization. - pH < 7.2 or Bicarbonate < 15mEQ/L before randomization. - Use of another diuretic in addition to furosemide before randomization. Dapagliflozin or Empagliflozin can be maintained upon admission or initiated early during hospitalization if desired by the treating physician (variable to be recorded). - Patients who cannot achieve adequate recording of variables (e.g., inability to quantify diuresis or weight). - Pregnant or lactating individuals. If of childbearing age and there is inconsistency with contraceptive use or reasonable doubts about current pregnancy, a pregnancy test must be conducted before study entry. |
Country | Name | City | State |
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n/a |
Lead Sponsor | Collaborator |
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Clinica Alemana de Santiago |
Appiani F. [Monitoring decongestion in acute heart failure]. Rev Med Chil. 2022 Apr;150(4):493-504. doi: 10.4067/S0034-98872022000400493. Spanish. — View Citation
Felker GM, Ellison DH, Mullens W, Cox ZL, Testani JM. Diuretic Therapy for Patients With Heart Failure: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Mar 17;75(10):1178-1195. doi: 10.1016/j.jacc.2019.12.059. — View Citation
Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O'Connor CM; NHLBI Heart Failure Clinical Research Network. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011 Mar 3;364(9):797-805. doi: 10.1056/NEJMoa1005419. — View Citation
Mullens W, Dauw J, Martens P, Verbrugge FH, Nijst P, Meekers E, Tartaglia K, Chenot F, Moubayed S, Dierckx R, Blouard P, Troisfontaines P, Derthoo D, Smolders W, Bruckers L, Droogne W, Ter Maaten JM, Damman K, Lassus J, Mebazaa A, Filippatos G, Ruschitzka F, Dupont M; ADVOR Study Group. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload. N Engl J Med. 2022 Sep 29;387(13):1185-1195. doi: 10.1056/NEJMoa2203094. Epub 2022 Aug 27. — View Citation
Rivas-Lasarte M, Maestro A, Fernandez-Martinez J, Lopez-Lopez L, Sole-Gonzalez E, Vives-Borras M, Montero S, Mesado N, Pirla MJ, Mirabet S, Fluvia P, Brossa V, Sionis A, Roig E, Cinca J, Alvarez-Garcia J. Prevalence and prognostic impact of subclinical pulmonary congestion at discharge in patients with acute heart failure. ESC Heart Fail. 2020 Oct;7(5):2621-2628. doi: 10.1002/ehf2.12842. Epub 2020 Jul 7. — View Citation
Trullas JC, Morales-Rull JL, Casado J, Carrera-Izquierdo M, Sanchez-Marteles M, Conde-Martel A, Davila-Ramos MF, Llacer P, Salamanca-Bautista P, Perez-Silvestre J, Plasin MA, Cerqueiro JM, Gil P, Formiga F, Manzano L; CLOROTIC trial investigators. Combining loop with thiazide diuretics for decompensated heart failure: the CLOROTIC trial. Eur Heart J. 2023 Feb 1;44(5):411-421. doi: 10.1093/eurheartj/ehac689. — View Citation
Urbich M, Globe G, Pantiri K, Heisen M, Bennison C, Wirtz HS, Di Tanna GL. A Systematic Review of Medical Costs Associated with Heart Failure in the USA (2014-2020). Pharmacoeconomics. 2020 Nov;38(11):1219-1236. doi: 10.1007/s40273-020-00952-0. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Any adverse event | Any adverse clinical event related to intervention during the first 3 months after start of the study | 3 months | |
Other | Changes in pH value | Change in pH over the specified time period | 4 days | |
Other | Change in plasma electrolyte values | Change in plasma concentration of sodium, potassium, and chloride | 4 days | |
Primary | Treatment success | Complete decongestion by the third morning without requiring escalation in diuretic therapy (by the second morning). | 4 days | |
Secondary | Mortality | All-cause mortality during the first 3 months after start of the study | 3 months | |
Secondary | Worsening Heart Failure | Readmission for Heart Failure or Urgent visit for Heart Failure during the first 3 months after start of the study | 3 months | |
Secondary | Cumulative 24-hour Natriuresis | Natriuresis measured on the second day | Day 2 | |
Secondary | Cumulative weight loss | Cumulative weight loss by the third morning | 4 days | |
Secondary | Subclinical congestion | Congestion score will be the score used in the study to evaluate the primary outcome. The calculated scores can range from 0 to 12 points, with 0 indicating absence of congestion and 12 representing the highest degree of congestion. The primary outcome will be defined as achieving a score of 0 or 1 and also having absence of B-lines in the lung ultrasound (negative LUS criterion). In this secondary outcome, the presence of subclinical congestion will be evaluated, which is defined as a congestion score of 0 or 1 but with a positive LUS. | 4 days | |
Secondary | Change in Hematocrit value | Change in Hematocrit | 4 days | |
Secondary | Change in NT-proBNP concentration | Change in NT-proBNP | 4 days | |
Secondary | Change in CA125 value | Change in CA125 | 4 days |
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