2024-517612-29-00已完成4 期
A Multicenter, Randomized, Double-Blind, Parallel Group, Placebo-Controlled Trial to Evaluate the Effect of In-Hospital Initiation of Dapagliflozin on Clinical Outcomes in Patients Who Have Been Stabilized During Hospitalization for Acute Heart Failure
The Brigham And Women’s Hospital Inc.49 个研究点 分布在 3 个国家目标入组 1,000 人开始时间: 2024年11月15日最近更新:
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,000
- 试验地点
- 49
- 主要终点
- Time to first occurrence of cardiovascular death or worsening heart failure defined as: 1. Worsening HF during the index admission requiring at least one of the following: a) initiation or re-initiation of inotropic therapy for ≥24 hours b) mechanical circulatory support c) invasive ventilatory support for heart failure d) heart transplantation
研究概览
简要总结
To assess the effect of in-hospital initiation of dapagliflozin, as compared with placebo, on the clinical outcome of cardiovascular death or worsening heart failure in patients who have been stabilized during hospitalization for acute heart failure.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •To evaluate the safety and tolerability of in-hospital initiation of dapagliflozin in this patient population.
- •Currently hospitalized for AHF defined as meeting all the following criteria: a) Presentation with worsening symptoms of heart failure (e.g., worsening dyspnea or dyspnea at rest, progressive fatigue, rapid weight gain, worsening edema/abdominal distention/anasarca) b) Objective signs or diagnostic testing consistent with volume overload (e.g., jugular venous distension, pulmonary basilar crackles, S3 gallop, ascites, hepatomegaly, peripheral edema, radiological evidence of pulmonary congestion, noninvasive or invasive hemodynamic evidence of elevated filling pressures) c) Intensification of AHF therapy during admission defined as at least one of the following: i. Augmentation of oral diuretic therapy [e.g., ≥2x outpatient regimen dose, addition of a second diuretic agent, or new initiation of diuretic therapy in a previously naïve patient] ii. Initiation of intravenous diuretic therapy iii. Initiation of intravenous vasoactive agent (e.g., inotrope or vasodilator) The majority of enrolled patients should have an established history of heart failure (defined as present for ≥2 months and for which the patient is on treatment). Trial leadership will monitor this proportion and may cap enrollment of patients without an established history of heart failure (i.e., patients presenting with de novo heart failure).
- •Left ventricular ejection fraction (LVEF) measured within the past 12 months (including during the current hospitalization)
- •Elevated NT-proBNP or BNP during current hospitalization: a) For patients with LVEF ≤40%: NT-proBNP ≥1600 pg/mL or BNP ≥400 pg/mL (NT-proBNP ≥2400 pg/mL or BNP ≥600 pg/mL if patient in atrial fibrillation or atrial flutter) b) For patients with LVEF >40%: NT-proBNP ≥1200 pg/mL or BNP ≥300 pg/mL (NT-proBNP ≥1800 pg/mL or BNP ≥450 pg/mL if patient in atrial fibrillation or atrial flutter)
- •Eligible patients will be randomized no earlier than 24 hours and up to 14 days after presentation while still hospitalized once they have been stabilized, as defined by: a) No increase (i.e., intensification) in the dose of intravenous diuretics during the 12 hours prior to randomization b) No use of intravenous vasodilators or inotropes during the 24 hours prior to randomization Patients across the spectrum of LVEF are eligible for participation in the trial. Trial leadership will monitor the proportion of patients with various LVEFs and may cap enrollment of certain subgroups to ensure a broad population. In addition, patients with and without type 2 diabetes are eligible for participation in the trial. Trial leadership will monitor the proportion of patients with and without type 2 diabetes and may cap enrollment of one subgroup to ensure adequate representation of the other.
排除标准
- •Symptomatic hypotension in the past 24 hours
- •Untreated sustained ventricular arrhythmias or Mobitz type II or third-degree heart block (i.e., without an ICD or pacemaker, respectively)
- •History of heart transplantation or current transplant listing; mechanical circulatory support use (either durable or temporary) during the index hospitalization
- •History of heart failure due to restrictive or infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy, uncorrected primary valvular disease, complex congenital heart disease, or heart failure felt to be due to a transient process (e.g., stress [takotsubo] cardiomyopathy, tachycardia-induced cardiomyopathy) expected to resolve within 2 months.
- •History of end-stage liver disease
- •Women of child-bearing potential (unless using highly effective contraception method) or currently breastfeeding
- •Current participation in a clinical trial with an unlicensed drug or device
- •Study staff or their family members
- •Any condition that, in the opinion of the investigator, would make trial participation not in the best interest of the subject, or would compromise compliance with the trial protocol (e.g., active severe infection, active malignancy)
- •Concurrent use of two or more intravenous inotropic agents during the index hospitalization
- •eGFR <25 ml/min/1.73 m2 as measured by the CKD-EPI equation at screening or rapidly progressive renal disease
- •Current use of an SGLT2 inhibitor
- •Prior intolerance of SGLT2 inhibitors, including hypersensitivity to dapagliflozin, or to any excipient (inactive substance) in the study drug
- •Type 1 diabetes mellitus or history of diabetic ketoacidosis
- •(Only applies to patients with T2DM who are on insulin and/or a sulfonylurea) History of recurrent major hypoglycemia (i.e., resulting in severe impairment in consciousness or behavior, or requiring emergency external assistance)
- •Implantation of a cardiac resynchronization therapy (CRT) device or valve repair or replacement within 30 days prior to randomization or intent to do so during the trial
- •ST-segment elevation myocardial infarction or coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) within 30 days prior to randomization or intent to undergo coronary revascularization during the trial
结局指标
主要结局
Time to first occurrence of cardiovascular death or worsening heart failure defined as: 1. Worsening HF during the index admission requiring at least one of the following: a) initiation or re-initiation of inotropic therapy for ≥24 hours b) mechanical circulatory support c) invasive ventilatory support for heart failure d) heart transplantation
Time to first occurrence of cardiovascular death or worsening heart failure defined as: 1. Worsening HF during the index admission requiring at least one of the following: a) initiation or re-initiation of inotropic therapy for ≥24 hours b) mechanical circulatory support c) invasive ventilatory support for heart failure d) heart transplantation
Time to first occurrence of cardiovascular death or worsening heart failure defined as: 2. Readmission for worsening heart failure
Time to first occurrence of cardiovascular death or worsening heart failure defined as: 2. Readmission for worsening heart failure
Time to first occurrence of cardiovascular death or worsening heart failure defined as: 3. Worsening heart failure leading to an urgent visit with administration of intravenous diuretic therapy (e.g., outpatient setting, emergency department) without associated hospital admission
Time to first occurrence of cardiovascular death or worsening heart failure defined as: 3. Worsening heart failure leading to an urgent visit with administration of intravenous diuretic therapy (e.g., outpatient setting, emergency department) without associated hospital admission
次要结局
- Symptomatic hypotension leading to hospitalization or study drug discontinuation
- Worsening renal function that results in at least a doubling of serum creatinine, hospitalization, study drug discontinuation, dialysis, or renal death
研究者
Wiviott Stephen
Scientific
The Brigham And Women’s Hospital Inc.
研究点 (49)
Loading locations...
相似试验
已完成
3 期
Ertugliflozin Pediatric StudyType 2 Diabetes Mellitus2022-501085-21-00Merck Sharp & Dohme LLC20
招募中
3 期
A trial to learn how well baxdrostat with dapagliflozin works compared to dapagliflozin on clinical outcomes alone and how safe it is in adults with chronic kidney disease (CKD) and high blood pressure2023-506460-14-00Astrazeneca AB1,310
招募中
3 期
Effects of continued administration of empagliflozin in patients with heart failure on active SGLT2 inhibitor treatment admitted for acute decompensated heart failureacute decompensated heart failure2024-517977-26-00Friedrich-Schiller-Universitaet Jena556
招募中
3 期
A Phase 3 program evaluating the effect of filgotinib in subjects with active axial spondyloarthritis2022-501354-10-01Alfasigma S.p.A.487
招募中
4 期
Early use of dapagliflozin in patients with acute myocardial infarction and reduced ejection fraction: the randomized ARMYDA-9 Dapagliflozin trialAcute Myocardial Infarction2025-521481-10-00Azienda Ospedaliero-Universitaria Maggiore Della Carita140