Aldosterone Targeted Neurohormonal Combined With Natriuresis Therapy - HF (ATHENA-HF)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 360
- 试验地点
- 22
- 主要终点
- 96 Hour Change in NT-proBNP
研究概览
简要总结
The primary objective of this study is to test the hypothesis that high-dose spironolactone will lead to greater proportional reduction in NT-proBNP levels from randomization to 96 hours over standard of care.
详细描述
Mineralocorticoid receptor antagonist (MRA) therapy is recommended in stable chronic systolic heart failure (HF) and post-infarction HF patients for improving morbidity and mortality. MRA therapy in AHF and in high doses is less well studied. The effectiveness and safety of early high dose MRA therapy in AHF is supported by a single-blind study showing lower risk of worsening renal function and need for loop diuretics, and improved congestion. MRA therapy in AHF may improve outcomes by relieving congestion at higher doses through their natriuretic property, in addition to preventing the deleterious effects of exacerbation of neuro-hormonal activation by loop diuretics.
This randomized, double blind, placebo-controlled study of high-dose spironolactone vs. placebo (for patients not receiving MRA at home) or low-dose spironolactone (for patients already receiving low-dose spironolactone) in AHF, will enroll 360 participants at approximately 30 clinical centers. After obtaining informed consent, subjects who fulfill all the inclusion criteria and none of the exclusion criteria will be randomized. Randomization will be performed by using procedures determined by the Coordinating Center (CC).
- Patients receiving no MRA therapy at baseline will be randomized to receive either spironolactone 100 mg or placebo daily for 96 hours.
- Patients already receiving low-dose spironolactone at baseline (12.5 mg or 25 mg daily) will be randomized to 100 mg or 25 mg spironolactone daily for 96 hours.
Within 24 hours prior to randomization, all study participants will undergo:
- Medical History
- Review of medications including pre-hospital loop diuretics, MRA, and potassium doses
- Physical examination, vital signs and body weight
- Measurement of creatinine, blood urea nitrogen (BUN), and electrolytes
- Dyspnea Relief Assessments (7-point Likert and Visual Analog Scale)
- Serum pregnancy test for all women of childbearing potential
- Collection of samples for measurement of NT-proBNP levels (Core Lab)
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patient ≥21 years old
- •Admitted to hospital for AHF with at least 1 symptom (dyspnea, orthopnea, or fatigue) and 1 sign (rales on auscultation, peripheral edema, ascites, pulmonary vascular congestion on chest radiography) of congestion
- •Patient must be randomized within 24 hours of first IV diuretic dose administered for the current episode of decompensation (regardless of where the diuretic was given e.g. office, ED, ambulance, hospital etc.)
- •Estimated GFR of ≥30 mL/min/1.73m2 determined by the MDRD equation
- •Serum K+ ≤5.0 mmol/L at enrollment
- •NT-proBNP ≥1000 pg/mL or BNP ≥250 pg/mL, measured within 24h from randomization
- •Not on MRA or on low-dose spironolactone (12.5 mg or 25 mg daily) at baseline
排除标准
- •Taking eplerenone or >25 mg spironolactone at baseline
- •eGFR < 30 ml/min/1.73m2
- •Serum K+ >5.0 mmol/L. If a repeat measurement within the enrollment window is <5.0, the patient can be considered for inclusion.
- •Systolic blood pressure <90 mmHg
- •Hemodynamically significant arrhythmias or defibrillator shock within 1 week
- •Acute coronary syndrome currently suspected or within the past 4 weeks
- •Severe liver disease (ALT or AST >3 x normal, alkaline phosphatase or bilirubin >2x normal)
- •Active infection (current use of oral or IV antimicrobial agents)
- •Active gastrointestinal bleeding
- •Active malignancy other than non-melanoma skin cancers
- •Current or planned mechanical circulatory support within 30 days
- •Post cardiac transplant or listed for transplant and expected to receive one within 30 days
- •Current inotrope use
- •Complex congenital heart disease
- •Primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy, acute myocarditis, constrictive pericarditis or tamponade
- •Previous adverse reaction to MRAs
- •Enrollment in another randomized clinical trial during index hospitalization
研究组 & 干预措施
Spironolactone
Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours
干预措施: Spironolactone (Drug)
Placebo
Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours
干预措施: Placebo (Drug)
结局指标
主要结局
96 Hour Change in NT-proBNP
时间窗: Randomization to 96 hours
The Core Laboratory at Vermont will determine NT-proBNP levels for calculation of the endpoint from samples obtained at randomization and 96 hours respectively. NT-proBNP was converted to log scale.
次要结局
- 96 Hour Change in Serum Creatinine(Randomization through 96 hours)
- 96 Hour Net Fluid Output(Randomization through 96 hours)
- 96 Hour Change in Body Weight(Randomization through 96 hours or earlier discharge)
- 96 Hour Change in Dyspnea Likert Score(Randomization through 96 hours)
- 96 Hour Change in Clinical Congestion Score(Randomization through 96 hours)
- 96 Hour Change in Serum Potassium Levels(Baseline, 96 hours)
- Change in Loop Diuretics Requirements From Baseline to 30 Days(Randomization through Day 30)
- Presence of Outpatient Worsening Heart Failure Symptoms Through Day 30(Hospital discharge through Day 30)
- 96 Hour Change in Dyspnea Visual Analog Scale(Randomization to 96 hours)