Acetazolamide or Metolazone in Acute Heart Failure
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 1,050
- 主要终点
- Treatment success
研究概览
简要总结
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.
详细描述
After inclusion in the study and signing the informed consent, the patient will be randomized into one of the following three intervention groups:
- Group A: Intravenous furosemide alone.
- Group B: Intravenous furosemide with oral metolazone 2.5mg.
- Group C: Intravenous furosemide with oral acetazolamide 250mg.
Metolazone or acetazolamide will be administered in fixed doses for a total of 3 doses (D0, D1, and D2) - at admission (D0), on the morning of the second day (D1), and on the morning of the third day (D2).
The use of intravenous furosemide will follow a protocol for dose and frequency of administration. Its dose should not be modified before D2. On D2, modification is allowed according to the protocol (details later).
In cases of major adverse events only, the local practitioner may suspend these therapies (as indicated later).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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/1.73m
- •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.
研究组 & 干预措施
Furosemide alone
Active comparator arm with intravenous furosemide dosing based on glomerular filtration rate (protocol).
干预措施: Furosemide Injection (Drug)
Acetazolamide plus Furosemide
Experimental arm number 1 corresponds to oral acetazolamide 250mg (once daily) in combination with furosemide according to the protocol.
干预措施: Acetazolamide 250 MG (Drug)
Acetazolamide plus Furosemide
Experimental arm number 1 corresponds to oral acetazolamide 250mg (once daily) in combination with furosemide according to the protocol.
干预措施: Furosemide Injection (Drug)
Metolazone plus Furosemide
Experimental arm number 2 corresponds to oral metolazone 2.5mg (once daily) in combination with furosemide according to the protocol.
干预措施: Metolazone 2.5 MG (Drug)
Metolazone plus Furosemide
Experimental arm number 2 corresponds to oral metolazone 2.5mg (once daily) in combination with furosemide according to the protocol.
干预措施: Furosemide Injection (Drug)
结局指标
主要结局
Treatment success
时间窗: 4 days
Complete decongestion by the third morning without requiring escalation in diuretic therapy (by the second morning).
次要结局
- Change in CA125 value(4 days)
- Mortality(3 months)
- Worsening Heart Failure(3 months)
- Cumulative 24-hour Natriuresis(Day 2)
- Cumulative weight loss(4 days)
- Subclinical congestion(4 days)
- Change in Hematocrit value(4 days)
- Change in NT-proBNP concentration(4 days)