Randomized Trial of Sodium-glucose Cotransporter 2 Inhibition in Heart Transplant Recipients
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 6
- 主要终点
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
研究概览
简要总结
Heart transplant (HTx) is an established therapy for advanced heart disease that restores quality of life and improves survival. However, due to preexisting comorbidities combined with the immunosuppressive therapies required after transplantation, HTx recipients remain at high risk for kidney, cardiovascular (CV), and metabolic disease. Large randomized clinical trials have recently shown that sodium-glucose cotransporter 2 inhibitors (SGLT2i) have potent kidney protective and CV benefits in many populations of patients with chronic kidney disease (CKD), CV disease and/or diabetes. SGLT2i have not been studied prospectively in HTx recipients, which represents a barrier to their use in this population.
In this multicenter randomized controlled trial in Veterans with HTx, investigators will evaluate the potential benefits of empagliflozin on kidney function, cardiometabolic risk, erythropoiesis, and functional status. A total of 200 Veterans will be randomly assigned to receive either empagliflozin 10 mg daily or a matching placebo for 12 months.
详细描述
Heart transplant (HTx) markedly improves patient health-related quality of life (hrQoL) and survival in advanced heart failure (HF). However, HTx recipients remain at elevated risk for kidney and cardiovascular (CV) morbidity and mortality. Mitigating the negative effects of these morbidities on long-term survival and on patient hrQoL after HTx is a critical unmet need. Large clinical trials have recently shown that sodium glucose cotransporter 2 inhibitors (SGLT2i) have potent kidney protective and CV benefits. By preventing glucose reabsorption in the renal proximal tubule and promoting glycosuria, SGLT2i trigger multiple downstream effects, including improvement in insulin sensitivity and in mitochondrial efficiency in kidney and heart. SGLT2i also modulate sympathetic activity, improve endothelial function and reduce inflammation, with resultant improvement in myocardial and vascular function. SGLT2i increase erythropoietin levels and improve iron utilization. HTx is often complicated by development of chronic kidney disease (CKD), diabetes mellitus (T2D), anemia, and CV events, especially cardiac allograft vasculopathy (CAV). Although SGLT2i may significantly reduce development of these complications, prospective studies of SGLT2i did not include transplant recipients, leaving an important knowledge gap. HTx recipients could derive particularly significant benefits from SGLT2i therapy. The investigators hypothesize that SGLT2i with empagliflozin in HTx recipients will result in beneficial effects on kidney function, cardiometabolic risk, erythropoiesis and functional status, and that SGLT2i use in this population will be safe and well tolerated. The specific aims of this study are:
Specific Aim 1. Investigate the effects of SGLT2i with empagliflozin on kidney function in HTx recipients.
Kidney disease after HTx is a potent predictor of mortality. Investigators hypothesize that treatment with empagliflozin will preserve kidney function after HTx.
Aim 1a. Assess the effects of SGLT2i on urinary albumin-to-creatinine ratio (UACR). Albuminuria, represented by UACR and an independent predictor of kidney outcomes, was consistently reduced by SGLT2i in the landmark trials of SGLT2i. Approximately 50% of Veterans after HTx have at least moderate albuminuria. Investigators hypothesize that empagliflozin therapy will decrease albuminuria in HTx recipients.
Aim 1b. Assess the effect of SGLT2i on estimated glomerular filtration rate (eGFR).
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
All subjects will be randomized to either empagliflozin 10 mg daily for 12 months or matching placebo. The subjects and the investigators will not know whether subjects are randomized to active arm (empagliflozin) or to control arm (placebo).
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
- •Age 18 years or older
- •Heart transplant recipient, 3 months after transplant
排除标准
- •eGFR <20 mL/min/1.73m2
- •Type 1 diabetes mellitus
- •HbA1C >10%
- •Baseline UACR <30 mg/g in patients without T2D
- •Known allergy or intolerance to SGLT2i
- •Active uncontrolled infection
- •Multiorgan transplant
- •SGLT2i treatment in the last 30 days
- •Pregnancy, breast-feeding or woman of child-bearing age not on birth control
研究组 & 干预措施
Placebo
A starting dose of empagliflozin 10 mg or matching placebo will be initiated after randomization and completion of the baseline testing. Participating subjects will remain at this dose for the whole study duration of 12 months.
干预措施: Placebo (Drug)
Empagliflozin
A starting dose of empagliflozin 10 mg or matching placebo will be initiated after randomization and completion of the baseline testing. Participating subjects will remain at this dose for the whole study duration of 12 months.
干预措施: Empagliflozin (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
时间窗: 12 months
Adverse and serious adverse events difference in active arm vs control arm
Urinary albumin-to-creatinine ratio (UACR)
时间窗: 12 months
UACR difference (mg/g) in subjects in active arm vs control arm
次要结局
- Hematocrit(12 months)
- Estimated Glomerular Filtration Rate (eGFR)(12 months)
- Hemoglobin A1c (HbA1c)(12 months)
- Serum interleukin 1b(IL-1b)(12 months)
- Serum tumor necrosis factor -a (TNF-a)(12 months)
- Serum interleukin 6 (IL-6)(12 months)
- Fasting blood glucose(12 months)
- Body weight(12 months)
- Systolic and diastolic blood pressure(12 months)
- Serum high sensitivity C-reactive protein (hsCRP)(12 months)
- Serum N-Terminal Pro-B-Type Natriuretic Peptide (NTproBNP)(12 months)
- Hemoglobin(12 months)
- Serum erythropoietin(12 months)
- Serum transferrin saturation(12 months)
- Six Minute Walk Test(12 months)
- Serum high sensitivity Troponin(12 months)
- Kansas City Cardiomyopathy Questionnaire-12(12 months)