Diuretic Strategies in Acute Heart Failure Patients At High Risk for Diuretic Resistance (P-Value-AHF): a Multicentre, Randomized, Parallel-group, Open-label Trial
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Diuretic efficacy after 6h
研究概览
简要总结
The P-VALUE-AHF trial is a multicenter, randomized, open-label, parallel-group trial on the diuretic and decongestive effects of different diuretic escalation strategies in patients with acute heart failure and diuretic resistance.
The main aims are
- to compare the diuretic efficacy of three therapeutic strategies in patients with acute heart failure and diuretic resistance.
- to assess the improvement in clinical congestion and to compare the symptom-relief among the different treatment regimens
详细描述
The P-VALUE-AHF trial is a multicenter, randomized, open-label, parallel-group trial on the diuretic and decongestive effects of different diuretic escalation strategies in patients with acute heart failure (AHF) and diuretic resistance (DR).
Consenting patients with AHF and DR will be will be randomized towards 3 diuretic regimens. Two to five hours after the initial standard dose Furosemide i.v,
- the first group will receive a doubled dose Furosemide (group FF)
- the second group will receive a combination of standard dose Furosemide and Metolazone (group FM)
- the third group will receive a combination of standard dose Furosemide and Acetazolamide (group FA)
Objectives
- The primary objective is to compare the diuretic efficacy (measured as natriuresis and urine volume) of three therapeutic strategies in patients with acute heart failure and diuretic resistance.
- The secondary objective is to assess the improvement in clinical congestion (EVEREST congestion score) and to compare the symptom-relief (improvement of dyspnoea (VAS)) among the different treatment regimens (FF vs. FM vs. FA).
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Elective or emergency hospital admission with clinical diagnosis of acute heart failure
- •One or more clinical signs of volume overload (i.e., peripheral edema, pleural effusion, jugular venous distension)
- •Low diuretic efficacy in the first 2 hours after the standard screening dose Furosemide i.v. (i.e., urine volume < 300 ml and urine sodium concentration < 70 mmol/L)
- •Plasma N terminal-proBNP level at enrolment > 1000 ng/L
- •Signed Informed Consent form
排除标准
- •Maintenance treatment with Acetazolamide or Metolazone
- •Use of any non-protocol defined diuretic agent that cannot be stopped upon study inclusion except for sodium-glucose co-transporter-2 inhibitors (e.g., dapagliflozin, empagliflozin, canagliflozin) and mineralocorticoid receptor antagonists (e.g., spironolactone, eplerenone)
- •Systolic blood pressure < 90 mmHg
- •Expected use of intravenous vasopressors (e.g., noradrenaline, adrenaline), inotropes (e.g., dobutamine, milrinone, levosimendan) at any time point during the study
- •Severe chronic kidney disease (estimated glomerular filtration rate < 15 ml/min/1.73 m2) or use of renal replacement therapy at any time before study inclusion
- •Severe liver dysfunction or cirrhosis at risk of hepatic encephalopathy
- •Severe electrolyte disturbances or metabolic acidosis requiring specific intravenous treatment
- •Concurrent diagnosis of acute coronary syndrome requiring urgent revascularization
- •History of cardiac transplantation or ventricular assist device
- •Allergy, intolerance or other contraindication against one of the study drugs
- •Pregnancy or breastfeeding
- •Age below 18 years.
研究组 & 干预措施
group FF
Group FF will receive a doubled dose Furosemide i.v.
The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v.
Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection.
干预措施: Furosemide (Drug)
group FM
Group FM will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o.
The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v.
Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection. Metolazone will be administered orally.
干预措施: Furosemide (Drug)
group FM
Group FM will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o.
The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v.
Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection. Metolazone will be administered orally.
干预措施: Metolazone (Drug)
group FA
Group FA will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v.
The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v.
Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection. Acetazolamide (500mg) will be administered intravenously as a short infusion.
干预措施: Furosemide (Drug)
group FA
Group FA will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v.
The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v.
Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection. Acetazolamide (500mg) will be administered intravenously as a short infusion.
干预措施: Acetazolamide (Drug)
结局指标
主要结局
Diuretic efficacy after 6h
时间窗: 6 hours after administration of the study-specific diuretic regimen
urine- natrium concentration (mmol/L)
次要结局
- Change in clinical congestion(0 and 24 hours after administration of the study-specific diuretic regimen)
- Diuretic efficacy after 2h(2 hours after administration of the study-specific diuretic regimen)
- Change in dyspnea severity(0 and 24 hours after administration of the study-specific diuretic regimen.)
- Diuretic efficacy after 24h(24 hours after administration of the study-specific diuretic regimen)