SGL-TX-PTDM: SGLT2i Effect on PTDM Development and Kidney Allograft Function in Kidney Transplant Recipients: A Randomized, Doubleblind, Placebo Controlled, National Multicenter Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 184
- 试验地点
- 3
- 主要终点
- Incidence of post-transplant diabetes mellitus (PTDM)
研究概览
简要总结
The goal of this clinical trial is to find out whether 12 months of treatment with the SGLT2 inhibitor Forxiga® (dapagliflozin 10 mg once daily), compared with placebo, can reduce the risk of developing post-transplant diabetes in kidney transplant recipients who do not have diabetes at the time of transplantation.
The main questions it aims to answer are:
- Does Forxiga reduce the risk of developing post-transplant diabetes and prediabetes compared with placebo?
- Does Forxiga help preserve the function of the transplanted kidney compared with placebo?
- Is Forxiga safe for kidney transplant recipients who do not have diabetes?
- Does Forxiga affect the occurrence of urinary tract infections, the amount of protein in the urine, and other kidney- and heart-related health measures compared with placebo?
Researchers will compare Forxiga with a placebo (a look-alike tablet containing no active medicine) to see whether it can reduce the risk of post-transplant diabetes while maintaining kidney function and remaining safe to use.
Adults who have recently received a kidney transplant and do not have diabetes may take part if they meet the study requirements.
Participants will be randomly assigned to receive either Forxiga or placebo once daily for 12 months. They will attend study visits 3, 6, and 12 months after joining the study. These visits will include health checks, blood tests, and urine tests. Neither the participants nor the study doctors will know which treatment each participant is receiving.
详细描述
Background Kidney transplantation is the best treatment of end-stage renal disease (ESRD), although median allograft survival is only 15 years. In non-transplant patients with chronic kidney disease (CKD) sodium-glucose co-transporter type 2 inhibitors (SGLT2i) protects kidney function and reduces decline in estimated glomerular filtration (eGFR) and in KTR with PTDM, SGLT2i improve glucose regulation.
Perspective With the current kidney transplant survival of average 15 years, app. one out of ten adult[1] kidney transplant recipients (KTR) outlive their donated kidneys. This poses a significant burden to the patients and society and increases the demand for new transplantations. WHO reported a 9% increase in the number of kidney transplant recipients from 2022 to 2023[2]. The growing population of kidney transplant recipients underscores the importance of research aimed at prolonging graft survival and preventing post-transplant diabetes mellitus (PTDM). The efficacy of SGLT2i on reducing PTDM incidence remain untested in KTR.
The SGL-TX-PTDM study aim to investigate the effect of SGLT2i on the incidence of PTDM. PTDM is associated with a 63% increased risk for graft failure and an 87% increased risk for death[8]. PTDM is therefore known to be a threat to graft and patient survival throughout many years [9]. In the long-term perspective, we hope to contribute with knowledge to preserve kidney transplant function, benefit society, and improve patients' quality of life.
Hypothesis We hypothesize that SGLT2i will reduce the incidence of PTDM in non-diabetic KTR as an add-on to standard-of-care.
Research Objective In this superior randomized controlled clinical trial we will determine the effect of oral SGLT2i compared with placebo as add-on to standard-of-care on incidence of PTDM in non-diabetic KTR.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Obtained written informed consent
- •Male or female patients, age ≥ 18 years.
- •Non-diabetic KTR
- •Immunosuppressive must include Tacrolimus
排除标准
- •Patients who is treated (diet or antidiabetics) for diabetes type 1 or 2 before randomization
- •eGFR< 25 ml/min/1.73m2 (before randomization)
- •Alanine aminotransferase (ALAT) > 3 x upper normal limit
- •Bilirubin > 2 x upper normal limit
- •Pregnancy
- •Positive plasma hCG
- •Breastfeeding
- •Known allergy towards SGLT2i or the content substance
- •Patients with chronic intestinal diseases, including inflammatory bowel diseases (e.g., Crohn's disease and ulcerative colitis) and structural conditions such as short bowel syndrome.
结局指标
主要结局
Incidence of post-transplant diabetes mellitus (PTDM)
时间窗: Follow up at 3,6 and 12 months after randomization
Domain: Post-transplant diabetes mellitus Specific measurement: Diagnosis of PTDM according to the American Diabetes Association (ADA) diagnostic criteria. Specific metric: Number of participants with PTDM Method of aggregation: Proportion of participants with PTDM in each treatment group (dapagliflozin versus placebo) Time point: 3, 6 and 12 months after randomization
次要结局
- Prediabetes status(Follow up at 3,6 and 12 months after randomization)
- Change in kidney allograft function(Follow up at 3,6 and 12 months after randomization)
- Change in proteinuria(Follow up at 3,6 and 12 months after randomization)
- Change in biochemical parameters(Follow up at 3,6 and 12 months after randomization)
- Urinary tract infections(Follow up at 3,6 and 12 months after randomization)
- Kidney transplant rejection(Follow up at 3,6 and 12 months after randomization)
- Renal composite outcome(Follow up at 3,6 and 12 months after randomization)
- Change in blood pressure(Follow up at 3,6 and 12 months after randomization)
- Out-of-target tacrolimus trough concentrations(Follow up at 3,6 and 12 months after randomization)
- Change in urinary biomarkers indicative of podocyte and tubular function(Baseline and 6 months follow up)
- Incidence of adverse events, serious adverse events, serious adverse reactions, all-cause mortality, and major adverse cardiovascular events (MACE)(Follow up at 12 months after randomization)