Short-term Effects of Dapagliflozin on Peak VO2 in Patients With Heart Failure With Reduced Ejection Fraction
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 74
- 试验地点
- 1
- 主要终点
- Functional capacity
研究概览
简要总结
This study will be a double-blind multicenter randomized study (1:1) to evaluate the effect of dapagliflozin 10 mg per day or placebo on short-term functional capacity evaluated through changes in peak oxygen consumption.
详细描述
This study will be a double-blind multicenter randomized study (1:1) to evaluate the effect of dapagliflozin 10 mg per day or placebo on short-term functional capacity evaluated through changes in peak oxygen consumption. This trial will include patients with stable symptomatic heart failure with reduced ejection fraction (HFrEF). Efficacy endpoints will be evaluated at 3 time points: 1) baseline (before dapagliflozin/placebo administration), 2) 30 days after randomization, and, 3) 90 days after randomization. An intermediate clinical visit will be performed one week after study initiation.
Pre-and post-treatment evaluations (at baseline, 30 and 90 days) will include clinical assessment, cardiopulmonary exercise stress test, echocardiography, 6-minute walk test (6MWT), and quality of life indicators (Minnesota Living with Heart Failure Questionnaire -MLHFQ).
The investigators postulate that dapagliflozin 10 mg/day improves short-term functional capacity of patients with symptomatic HFrEF through multifactorial mechanisms, such as diuretic effect and improvement in myocardial energetic efficiency.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
After providing informed consent, patients will be randomly assigned, with a remote, web-based computer-generated block randomization procedure in an allocation 1:1 ratio, to either receive dapagliflozin 10 mg per day or placebo (one tablet a day orally). This system will allow the maintenance of the randomization codes and the opening of them if necessary. Investigators and patients will be blinded to treatment allocations.
Knowing that no treatment crossings between both groups are expected, there is no need of planning washing periods.
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The participant or his legal representative is willing and able to give informed consent for participation in the study.
- •Male or female, aged ≥18 years.
- •Established documented diagnosis of symptomatic HF (NYHA functional class II-III), which has been present for at least 2 months.
- •LVEF ≤40% documented in the last 3 months by echocardiography or cardiac magnetic resonance.
- •NT-proBNP ≥600 pg/ml.
- •Patients should receive background standard of care for HFrEF at judgment of the investigator.
- •Estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73m2 (DMRD formula) at enrolment.
排除标准
- •Inability to perform a valid (respiratory exchange ratio -RER- ≥1.05) baseline cardiopulmonary exercise test (CPET)
- •Patients receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrolment, or previous intolerance of an SGLT2 inhibitor
- •Type 1 diabetes
- •Symptomatic hypotension or systolic blood pressure <95 mmHg
- •Current acute decompensated HF or hospitalization due to decompensated HF <4 weeks prior to enrolment
- •Myocardial infarction, unstable angina, stroke, or transient ischemic attack within 12 weeks prior to enrolment
- •Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) or cardiac valve repair/replacement within 12 weeks prior to enrolment, or planned to undergo any of these operations after randomization
- •Implantation of a cardiac resynchronization therapy (CRT) device within 12 weeks prior to enrolment or intent to implant a CRT device
- •Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or implantation expected after randomization
- •HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy, or uncorrected severe primary cardiac valve disease
- •Symptomatic bradycardia or second or third-degree heart block without a pacemaker
- •Severe renal dysfunction (eGFR<30 ml/min/1.73m2) or prior admission for acute renal failure in the last 4 weeks.
- •Pregnant or lactating women
- •Woman of childbearing age, unless they are using highly effective contraceptive methods.
- •Patients with severe hepatic impairment (Child-Pugh class C).
研究组 & 干预措施
Dapagliflozin 10 mg
After providing informed consent, patients will be randomly assigned to receive dapagliflozin 10 mg per day.
干预措施: Maximal functional capacity by cardiopulmonary exercise testing (Diagnostic Test)
Dapagliflozin 10 mg
After providing informed consent, patients will be randomly assigned to receive dapagliflozin 10 mg per day.
干预措施: Echocardiography (Diagnostic Test)
Dapagliflozin 10 mg
After providing informed consent, patients will be randomly assigned to receive dapagliflozin 10 mg per day.
干预措施: Evaluation of health related quality of life (Behavioral)
Dapagliflozin 10 mg
After providing informed consent, patients will be randomly assigned to receive dapagliflozin 10 mg per day.
干预措施: Submáximal functional capacity assesment by 6 minutes walk test (Diagnostic Test)
Dapagliflozin 10 mg
After providing informed consent, patients will be randomly assigned to receive dapagliflozin 10 mg per day.
干预措施: Clinical evaluation (Other)
Placebo identical to dapagliflozin 10 mg
After providing informed consent, patients will be randomly assigned to receive placebo (one tablet a day orally).
干预措施: Maximal functional capacity by cardiopulmonary exercise testing (Diagnostic Test)
Placebo identical to dapagliflozin 10 mg
After providing informed consent, patients will be randomly assigned to receive placebo (one tablet a day orally).
干预措施: Echocardiography (Diagnostic Test)
Placebo identical to dapagliflozin 10 mg
After providing informed consent, patients will be randomly assigned to receive placebo (one tablet a day orally).
干预措施: Evaluation of health related quality of life (Behavioral)
Placebo identical to dapagliflozin 10 mg
After providing informed consent, patients will be randomly assigned to receive placebo (one tablet a day orally).
干预措施: Submáximal functional capacity assesment by 6 minutes walk test (Diagnostic Test)
Placebo identical to dapagliflozin 10 mg
After providing informed consent, patients will be randomly assigned to receive placebo (one tablet a day orally).
干预措施: Clinical evaluation (Other)
结局指标
主要结局
Functional capacity
时间窗: At baseline, 30 and 90 days after starting treatment with dapagliflozin or placebo.
Changes in peak oxygen consumption (VO2) at baseline, 30 and 90 days after starting treatment with dapagliflozin or placebo. VO2 is only one measure and is expressed as milliliters of oxygen per kilogram of body weight per minute (oxygen in milliliters, weight in kilograms, and time in minutes and expressed in ml/kg/min).
次要结局
- Left atrial volume(At baseline, 30 and 90 days after starting treatment with dapagliflozin or placebo.)
- Evaluation of health related quality of life by Minnesota Living with Heart Failure Questionnaire (MLHFQ)(At 30 and 90 days after starting treatment with dapagliflozin or placebo.)
- Left ventricular volumes(At baseline, 30 and 90 days after starting treatment with dapagliflozin or placebo.)
- Left ventricular ejection fraction(At baseline, 30 and 90 days after starting treatment with dapagliflozin or placebo.)
- Submáximal functional capacity assesment by 6 minutes walk test(at 30 and 90 days after starting treatment with dapagliflozin or placebo.)
- Echocardiographic parameters of diastolic function(At baseline, 30 and 90 days after starting treatment with dapagliflozin or placebo.)
研究者
Julio Nuñez
Principal Investigator, Clinical Professor
Fundación para la Investigación del Hospital Clínico de Valencia