Clinical Outcomes of Dapagliflozin in Acute Heart Failure With Reduced Ejection Fraction, a Randomized Controlled Trial (CODA-HFrEF)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 117
- 试验地点
- 2
- 主要终点
- Length of hospital stay
研究概览
简要总结
The goal of this clinical trial is to evaluate the short-term clinical outcomes of starting Dapagliflozin on the same day of hospital admission in patients with acute decompensated heart failure (ADHF) with reduced ejection fraction.
The main questions it aims to answer are:
- Does early initiation of Dapagliflozin improve the length of hospital stay and in-hospital mortality in patients with ADHF?
- Does early initiation of Dapagliflozin enhance the diuretic response, weight reduction and pro-BNP reduction in the acute stage of HF?
- Does early initiation of Dapagliflozin adversely affect the hemodynamic stability and kidney functions in the acute stage of HF?
Participants will be randomized with the ratio of 1:1 within 24 hours of admission to receive Dapagliflozin 10 mg/day versus standard of care. Follow up will continue for 2 months after hospital discharge.
Researchers will compare the in-hospital and 60-day clinical outcomes in the Dapagliflozin group versus the standard treatment group.
详细描述
Background and Rationale:
With growing interest in studying the pharmacodynamics of SGLT-2 inhibitors, several cardio-protective mechanisms were defined beyond their diuretic effect. Those included anti-inflammatory effect and attenuation of oxidative stress in myocardial cells, renin-angiotensin aldosterone system blocking via activating AT-2 receptors, inhibition of Na+-H+ exchanger within myocardial cells , improving cardiac metabolomics via supplying more ketones , and weight reduction through lowering insulin secretion.
These findings invited more research to evaluate their benefit in patients having heart failure with reduced ejection fraction (HFrEF) regardless of diabetes mellitus (DM) status. Two large trials (DAPA-HF and EMPEROR-Reduced) have shown a consistent mortality benefit for SGLT-2 inhibitors in HFrEF patients in absence of DM.
Having a wide safety margin and low risk of complications, the use of SGLT-2 inhibitors was recently extended beyond the scope of cardiovascular disease to include patients with chronic kidney disease after their renal protective role was validated in CREDENCE and DAPA-CKD trials with significantly lower risk of albuminuria and disease progression.
Since most of the forementioned studies included patients with chronic HF who are stable on oral therapy, it has become urging to study the efficacy and safety of starting SGLT-2 inhibitors in patients with acute HF during the hospital phase. Ongoing trials have been investigating this issue recently, with pending outcomes. However, patients with de-novo AHF secondary to acute coronary syndrome have been excluded from these studies. Also, some of those studies started SGLT2 inhibitors only after stabilization of acute heart failure patients in-hospital.
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
- •Adult patients above 18 years presenting with acute heart failure defined as rapid development of dyspnea NYHA class III-IV associated with clinical signs of HF (e.g. congested neck veins, pulmonary rales, lower limb swelling, radiological evidence of pulmonary congestion) with LVEF ≤ 40%.
排除标准
- •Cardiogenic shock on admission, defined as SBP < 90 mmHg plus signs of peripheral hypoperfusion or the need of vasopressor or inotropic support.
- •Estimated GFR < 30 mL/min/1.73 m
- •Pregnancy or lactation.
- •Type I DM or history of DKA.
- •Treatment with any SGLT2 inhibitor in the last month.
- •Known intolerance to any SGLT2 inhibitor.
- •Severe anemia (Hemoglobin < 7 g/dl).
研究组 & 干预措施
Dapagliflozin group
This group will receive oral Dapagliflozin 10 mg once daily within 24 hours from hospital admission, in addition to the standard treatment for acute heart failure.
干预措施: Dapagliflozin 10mg Tab (Drug)
结局指标
主要结局
Length of hospital stay
时间窗: From the date of admission until the date of discharge, average of 7 days
The number of days from hospital admission to discharge.
Change in NT-proBNP at day 4 (or at discharge if earlier).
时间窗: First 4 days of hospital admission
The percentage change between baseline NT-proBNP on admission and NT-proBNP at day 4.
All-cause mortality during hospitalization.
时间窗: From the date of admission until the date of discharge, average of 7 days
Death from any cause during the period of hospital stay.
Diuretic response during the hospital phase.
时间窗: First 4 days of hospital admission
Defined as adjusted urine output and weight change per 40 mg of IV Furosemide or equivalent dose
次要结局
- Worsening renal functions(During hospital stay and up to 60 days after hospital discharge)
- Composite endpoint of cardiovascular death, re-admission for HF, or urgent clinic visit for decompensation at 2 months after hospital discharge.(60 days after hospital discharge)
- Change in serum NT-proBNP after 2 months.(60 days after hospital discharge)
- Composite endpoint of urogenital infections, hypoglycemic events, hypotension events or diabetic ketoacidosis.(During hospital stay and up to 60 days after hospital discharge)
研究者
Hossameldin Elsayed Khalifa Hussein
Assistant Lecturer of Cardiology
Cairo University