Efficacy and Mechanisms of Dapagliflozin in Promoting Kidney Function and Cardiovascular Health in Kidney Transplant Recipients
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Albuminuria
研究概览
简要总结
Long-term allograft function in kidney transplant recipients (KTRs) remain suboptimal, and graft failure causes significant morbidity and mortality, with cardiovascular disease being the leading cause of death in KTRs and the most common cause of death with a functioning graft. Sodium-glucose cotransporter 2 (SGLT2) inhibitors safely lower cardiovascular and kidney disease risk in the non-transplant population, yet data in KTRs are lacking. This clinical trial seeks to establish the efficacy and safety of dapagliflozin, a SGLT2 inhibitor, for improving cardiovascular and kidney graft function in adult KTRs with type 2 diabetes and post-transplant diabetes, and to leverage innovate translational methods to define the underlying mechanisms of action.
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)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-80 years
- •Kidney transplant received 1 year prior to randomization
- •estimated glomerular filtration rate 30-90 ml/min/1.73m2
- •Urine albumin to creatinine ratio (ACR) 30-5000 mg/g
- •Pre-existing type 2 diabetes or post-transplant diabetes mellitus
- •Blood pressure <130/80 mm Hg prior to randomization
- •Able to provide informed consent
- •Stable immunosuppression for at least 3 months prior to baseline consisting of tacrolimus, mycophenolate mofetil/mycophenolic acid and prednisone
- •Stable anti-hypertensive regimen for at least 1month prior to baseline
- •Stable diabetes management for at least 3 months prior to baseline
- •Stable angiotensin converting enzyme inhibitor/angiotensin receptor blocker use for at least 3 months prior to baseline (if applicable)
- •Glucagon-like peptide-1 receptor agonist (GLP-1RA) for at least 3 months prior to baseline (if applicable)
排除标准
- •Type 1 diabetes
- •Anticipated life expectancy <1 year
- •Uncontrolled hypertension
- •Hemoglobin A1c >9%
- •Body mass index >40 kg/m2
- •New York Heart Association Class 3 or 4 heart failure symptoms, an EF ≤30%, or hospitalization for heart failure in the past 3 months
- •Pregnancy, plans to become pregnant, or breastfeeding
- •Current use of sodium glucose cotransporter-2 (SGLT2) inhibitors
- •Current urinary or urogenital infection
- •Use of anticoagulants (contraindication to kidney biopsy)
- •Magnetic resonance imaging (MRI) contraindications
- •History of lower-limb amputation irrespective of etiology
- •Known hypersensitivity to dapagliflozin
研究组 & 干预措施
Dapagliflozin
Participants will receive dapagliflozin 10mg daily
干预措施: Dapagliflozin 10mg Tab (Drug)
Placebo
Participants will receive one placebo tablet daily
干预措施: Placebo (Drug)
结局指标
主要结局
Albuminuria
时间窗: Change from baseline to 12 months
Measured by urine albumin to creatinine ratio
次要结局
- Kidney morphometry, metabolomics from paired kidney biopsies(Change from baseline to 12 months)
- Left ventricular mass(Change from baseline to 12 months)
- estimated glomerular filtration rate(Change from baseline to 12 months)
- safety and tolerability(baseline, 6 and 12 months)
- Kidney fibrosis(Change from baseline to 12 months)
- Kidney oxygenation(Change from baseline to 12 months)
- Arterial stiffness(Change from baseline to 12 months)