Phase II Trial of Metformin for Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 2
- 主要终点
- The primary endpoint of the trial will be mean pulmonary artery pressure (mPAP) during submaximal exercise as compared between placebo and metformin at 12 weeks (i.e. the week 12 RHC of placebo vs week 12 RHC of metformin).
研究概览
简要总结
The main objective of this study is to determine the clinical efficacy of metformin versus placebo and the therapeutic response with regards to functional capacity and hemodynamics in PH-HFpEF.
详细描述
This is a 12-week blinded cross over trial of metformin in PH-HFpEF to improve exercise hemodynamics, functional capacity, and glucose metabolism. This phase II clinical trial will provide detailed phenotyping, physiological and mechanistic data on PH-HFpEF.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •2. PH-HFpEF Confirmed diagnosis by RHC within the past 6 months:
- •Mean Pulmonary Arterial Pressure (mPAP) ≥ 25 mm Hg AND Pulmonary artery wedge pressure (PAWP) ≥ 15 mm Hg AND Transpulmonary Gradient (TPG) ≥ 12 mm Hg
- •OR Exercise measurements
- •Mean Pulmonary Arterial Pressure (mPAP) ≥ 30 mm Hg AND Pulmonary artery wedge pressure (PAWP) ≥ 20 mm Hg AND PA calculation (change in mPAP/change in cardiac output) = ≥3 mmHg/L/min
- •3. Three or more features of metabolic syndrome defined as:
- •Body Mass Index (BMI) ≥ 30 kg/m² Systolic blood pressure (BP) ≥ 130 mm Hg and/or diastolic BP ≥ 85 mm Hg Elevated waist circumference > 102 cm in men and > 88 cm in women Fasting triglyceride (TG) level over 150 mg/dl High-density lipoprotein <40 mg/dL in men or < 50 mg/dL in women
排除标准
- •Age less than 18 years;
- •Uncontrolled systemic hypertension based on repeated measurement of sitting systolic blood pressure >170 mm Hg or sitting diastolic blood pressure >95 mm Hg at Screening;
- •Systemic sitting blood pressure < 110 mmHg systolic or < 60 mm Hg diastolic at Screening;
- •Hemoglobin A1C > 10;
- •Currently taking metformin or history of intolerance to metformin or contraindication to taking metformin;
- •Known type 1 diabetes
- •Positive urine pregnancy test or breastfeeding
- •Ejection Fraction < 50%
- •11. End-stage malignancy;
- •Major cardiovascular event or procedure within 6 weeks prior to enrollment;
- •Severe valvular disease;
- •Other severe acute or chronic medical, psychiatric or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study or would prevent completion of the study;
- •Current Smoker;
- •Hemoglobin <9 g/dL;
- •Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2;
- •Receipt of an investigational product or device, or participation in a drug research study within a period of 15 days
- •<3 months of stable dose of PDE5i
研究组 & 干预措施
Placebo Oral Capsule
Placebo capsule that is of identical size, shape, and color to experimental drug capsule PO (by mouth) BID (two times each day) for 12 weeks
干预措施: Placebo oral capsule (Drug)
Drug: Metformin
500mg PO (by mouth) BID (two times daily) x 1 week then increase to 1000mg PO BID x 11 weeks
干预措施: Metformin (Drug)
结局指标
主要结局
The primary endpoint of the trial will be mean pulmonary artery pressure (mPAP) during submaximal exercise as compared between placebo and metformin at 12 weeks (i.e. the week 12 RHC of placebo vs week 12 RHC of metformin).
时间窗: 12 weeks (i.e. the 12th week of placebo vs 12th week of metformin)
次要结局
未报告次要终点