Safety and Efficacy of Early, seQUential Oral dIuretic Nephron blockAde In Acute Heart Failure (SEEQUOIA-AHF)
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 206
- 试验地点
- 1
- 主要终点
- Body weight change at 96 hours since randomization
研究概览
简要总结
The SEEQUOIA-AHF (Safety and Efficacy of Early, seQUential oral dIuretic nephron blockAde in Acute Heart Failure) trial is a multicenter, randomized, open-label, parallel-arm trial assessing the impact of early sequential nephron blockade (i.e. a regimen based on the combination of four oral diuretics with different sites of action along the nephron at low doses) compared to a conventional approach with a high-dose loop diuretic in the treatment of congestion in patients hospitalized with acute heart failure (AHF).
In this study, after 24-72 hours of high-dose intravenous furosemide started at the time of hospital admission, patients admitted with AHF will be randomized to open-label oral treatment with either low-dose sequential nephron blockade or high-dose furosemide for 96 hours.
The primary end-point will be the bivariate change in body weight and serum creatinine value at 96 hours since randomization. Secondary endpoints will include clinical (e.g., total change in body weight during hospitalization, change in dyspnea score at 96 hours since randomization, 30-day readmission rate) and laboratory (e.g., change in BNP or NT-proBNP at discharge vs randomization) parameters, and safety (e.g., change in serum creatinine value at discharge versus randomization and up to 30 days from discharge) issues.
详细描述
The SEEQUOIA-AHF trial is aimed at ascertaining if the early, oral administration of a combination of four diuretics with different sites of action along sequential nephron segments (i.e., sequential nephron blockade: proximal tubule, loop of Henle, distal tubule, cortical collecting duct) may achieve greater decrease in body weight and lower increase in serum creatinine values as compared with standard of care, i.e. a conventional diuretic therapy regimen based on high-dose oral furosemide. To assess the efficacy and safety of an early sequential nephron blockade, the study intervention will be initiated 24-72 hours after an algorithm-based treatment with high-dose intravenous furosemide started at the time of hospital admission to achieve patient stabilization.
After 24-72 hours of algorithm-based treatment with high-dose intravenous furosemide, eligible patients will be randomized to either control (furosemide-only) or intervention (early sequential nephron blockade) arm.
All patients will be put on a low sodium diet (< 70 mEq/24 hours), and will be allowed a fluid intake of < 1 L/day.
Following randomization patients will be started on oral diuretic therapy according to two different approaches, namely:
- High-dose oral furosemide-only arm A furosemide oral dose equivalent to twice the intravenous dose of the last 24 hours will be given in two daily divided doses.
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
- •Male or non-pregnant female patient, 18 years or older
- •Patients admitted to Cardiology or Internal Medicine units with a diagnosis of acute decompensated heart failure and congestion: NT-proBNP > 1,000 pg/ml or BNP >250 pg/ml, dyspnea and at least two of the following clinical signs: 2+ pitting edema, pulmonary edema/pleural effusions at chest x-ray or US body weight increase above usual > 5% over the last 4 weeks
- •Clinically stable patients that can be switched to oral diuretic therapy after 24-72 hours of an algorithm-based treatment with high-dose intravenous furosemide started at the time of hospital admission
- •Patients capable to provide written informed consent
排除标准
- •Serum creatinine levels > 3.5 mg per deciliter at admission to the hospital or usual estimated glomerular filtration rate (eGFR) < 20 ml/min/1.73 m2 by the MDRD or CKD-EPI formula
- •Systolic blood pressure < 90 mmHg at time of enrollment and/or hemodynamic instability severe enough to require intravenous inotropes, intravenous vasodilators, or both
- •Severe arrhythmias with hemodynamic instability or DC shock occurred prior to randomization
- •Ascertained acute coronary syndrome (ACS), or ACS occurred within the last 4 weeks
- •Hematocrit > 45%
- •Use of iodinated radio contrast material occurred in the last 72 hours
- •Current mechanical ventilator support
- •Previous solid organ transplant
- •Primary hypertrophic or infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis or cardiac tamponade, severe valvular stenosis
- •Complex congenital heart disease
- •Liver disease (serum ALT or AST > 4, and/or total serum bilirubin > 3)
- •Known bilateral renal artery stenosis
- •Active sepsis or ongoing systemic infection
- •Active gastrointestinal tract bleeding
- •Enrollment in another clinical trial
- •Locally advanced or metastatic cancer
研究组 & 干预措施
Standard diuretic therapy (SDT)
Furosemide +/- spironolactone or potassium canrenoate
干预措施: Standard diuretic therapy (Drug)
Early sequential nephron blockade (ESNB)
Furosemide + metolazone + acetazolamide +/- spironolactone or potassium canrenoate
干预措施: Early sequential nephron blockade (Drug)
结局指标
主要结局
Body weight change at 96 hours since randomization
时间窗: 96 hours since randomization
Difference between body weight (in Kg) at 96 hours since randomization and the value at randomization
Serum creatinine change at 96 hours since randomization
时间窗: 96 hours since randomization
Difference between the concentration of serum creatinine (in mg/dL) at 96 hours since randomization and the value at randomization
次要结局
- Efficacy: Change in dyspnea score at 96 hours since randomization(96 hours since patient randomization)
- Safety: Change in serum creatinine value at discharge versus at randomization(Up to 30 days)
- Efficacy: Total weight change during hospitalization(Up to 30 days)
- Efficacy: Percent change in body weight at discharge versus at randomization(Up to 30 days)
- Efficacy: Total equivalent furosemide dose at 96 hours since randomization(96 hours since patient randomization)
- Efficacy: Proportion of patients requiring an increase in furosemide dose or switching to intravenous infusion within the first 96 hours since randomization(96 hours since patient randomization)
- Efficacy: Change in BNP or NT-pro BNP serum concentrations at discharge versus at randomization(Up to 30 days)
- Efficacy: Percentage of patients with BNP or NT-pro BNP decrease > 30% at discharge versus at randomization(Up to 30 days)
- Efficacy: Length-of-hospital stay(Up to 30 days)
- Safety: Change in serum creatinine concentration at 30 days since discharge versus at randomization(Since patient randomization to 30 days after discharge)
- Safety: Change in BUN/creatinine ratio at discharge versus at randomization(Up to 30 days)
- Safety: Change in BUN/creatinine ratio at 30 days since discharge versus at randomization(Since patient randomization to 30 days after discharge)
- Safety: Percentage of patients with WKF at 96 hours since randomization(96 hours since randomization)
- Safety: Percentage of patients with WKF at discharge versus at randomization(Up to 30 days)
- Safety: Percentage of patients with hyponatremia at 96 hours since randomization(96 hours since randomization)
- Efficacy: 30-day readmission rate(30 days since patient discharge)
- Safety: Change in BUN/creatinine ratio at 96 hours since randomization(96 hours since randomization)
- Safety: Percentage of patients with hypokalemia at 96 hours since randomization(96 hours since randomization)
- Safety: Percentage of patients with metabolic alkalosis at 96 hours since randomization(96 hours since randomization)
- Safety: Days with hypernatremia since randomization to discharge(Up to 30 days)
- Safety: Percentage of patients with severe hyponatremia at 96 hours since randomization(96 hours since randomization)
- Safety: Percentage of patients with hyperkalemia at 96 hours since randomization(96 hours since randomization)
- Safety: Percentage of patients with hypomagnesemia at 96 hours since randomization(96 hours since randomization)
- Safety: Days with severe hyponatremia since randomization to discharge(Up to 30 days)
- Safety: Days with hypokalemia since randomization to discharge(Up to 30 days)
- Safety: Days with metabolic alkalosis since randomization to discharge(Up to 30 days)
- Safety: Days with hypomagnesemia since randomization to discharge(Up to 30 days)
- Safety: Percentage of patients with hypernatremia at 96 hours since randomization(96 hours since randomization)
- Safety: Days with hyponatremia since randomization to discharge(Up to 30 days)
- Safety: Days with hyperkalemia since randomization to discharge(Up to 30 days)
研究者
Enrico Fiaccadori
Associate Professor of Nephrology
University of Parma