NCT04956809已完成2 期
Effect of Dapagliflozin on Submaximal Exercise Tolerance in Heart Failure
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- The primary endpoint will be the change in submaximal exercise endurance (time to exhaustion at 75% of peak workload) between Dapa and placebo.
研究概览
简要总结
This study will examine whether and how the FDA-approved drug dapagliflozin (Dapa) improves submaximal exercise endurance and skeletal muscle oxidative phosphorylation capacity (SkM OxPhos) in patients with heart failure and reduced left ventricular ejection fraction (HFrEF).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Diagnosis of HFrEF with NYHA Class II-III functional class, which has been present for at least two months
- •Left ventricular ejection fraction ≤ 40%
- •Stable medical therapy for at least 1 month
- •Plasma NT-proBNP level of: ≥ 200pg/mL; OR ≥ 125pg/mL if they were hospitalized for HF within the past 12 months; or ≥ 250 pg/mL if patient had atrial fibrillation/flutter on baseline ECG
排除标准
- •Receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrollment or previous intolerance of an SGLT2 inhibitor
- •Type 1 diabetes mellitus
- •Age <18 years old
- •Pregnancy: Women of childbearing potential will undergo a urine pregnancy test during the screening visit.
- •Uncontrolled atrial fibrillation, as defined by a resting heart rate > 100 beats per minute at the time of the baseline assessment
- •Paroxysmal atrial fibrillation (Afib) or flutter with >1 hour of continuous Afib documented within the previous 6 months (prior to screening or randomization), direct-current (DC) cardioversion or ablation procedure for Afib within 6 months, or plan to attempt to restore sinus rhythm (with drug therapy, ablation, or DC cardioversion) within 6 months of randomization. Subjects with persistent Afib and no sinus rhythm documented in the prior 6 months are permitted.
- •Hemoglobin < 10 g/dL
- •eGFR < 25 mL/min/1.73m^2, or unstable or rapidly progressing renal disease at the time of randomization
- •Subject inability/unwillingness to exercise
- •Greater than moderate left sided valvular disease (mitral regurgitation, aortic stenosis, aortic regurgitation), moderate or greater mitral stenosis, severe right-sided valvular disease
- •Known hypertrophic, infiltrative, restrictive or inflammatory cardiomyopathy
- •Clinically significant pericardial disease, as per investigator judgment
- •Current angina due to clinically significant epicardial coronary disease, as per investigator judgment
- •Acute coronary syndrome or coronary intervention within the past 2 months
- •Primary pulmonary artery hypertension (WHO Group 1 Pulmonary Arterial Hypertension)
- •Clinically significant lung disease as defined by: Chronic Obstructive Pulmonary Disease meeting Stage III or greater GOLD criteria (FEV1<50% predicted), treatment with oral steroids within the past 6 months for an exacerbation of obstructive lung disease, current use of supplemental oxygen aside from nocturnal oxygen for the treatment of obstructive sleep apnea.
- •Desaturation to <90% on the baseline maximal effort cardiopulmonary exercise test will also be grounds for exclusion
- •Clinically-significant ischemia, as per investigator's judgement, on stress testing without either (1) subsequent revascularization, (2) an angiogram demonstrating the absence of clinically significant epicardial coronary artery disease, as per investigator judgment; (3) a follow-up 'negative' stress test, particularly when using a more specific technique (i.e., a negative perfusion imaging test following a 'positive' ECG stress test)
- •Exercise induced regional wall motion abnormalities suggestive of ongoing ischemia during the baseline maximal effort cardiopulmonary exercise test will be exclusionary
- •Implantation of a CRT device within 12 weeks prior to enrollment or intent to implant a CRT device during the study period
- •Previous cardiac transplantation or implantation of a ventricular assist device, or implantation expected after randomization
- •Symptomatic bradycardia or second- or third-degree heart block, in the absence of a pacemaker
- •Significant liver disease impacting synthetic function or volume control (ALT/AST > 3x ULN, Albumin < 3.0 g/dL)
- •Severe right ventricular dysfunction
- •Baseline resting seated systolic blood pressure > 180 mmHg or <90 mmHg
- •Orthostatic blood pressure response to the transition from supine to standing (>20 mmHg reduction in systolic blood pressure 2-3 minutes after standing)
- •Active participation in another study that utilizes an investigational agent (observational studies/registries allowed)
- •Any condition that, in the opinion of the investigator, will interfere with the completion of the study. This may include comorbid or psychiatric conditions that may impede successful completion of the protocol, or logistical concerns (e.g. inability to travel to the exercise unit).
研究组 & 干预措施
Dapagliflozin 10mg
Active Comparator
Active arm will be 6 weeks in duration, separated by a 2-week wash-out period.
干预措施: Dapagliflozin 10Mg Tab (Drug)
Placebo
Placebo Comparator
Placebo arm will be 6 weeks in duration, separated by a 2-week wash-out period.
干预措施: Placebo (Drug)
结局指标
主要结局
The primary endpoint will be the change in submaximal exercise endurance (time to exhaustion at 75% of peak workload) between Dapa and placebo.
时间窗: 24 Months
次要结局
未报告次要终点
研究者
Kenneth B Margulies
Principal Investigator
University of Pennsylvania
研究点 (1)
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