Empagliflozin on Residual Kidney Function in Incident Peritoneal Dialysis Patients: a Pilot Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Medication adherence
研究概览
简要总结
Empagliflozin, a new class of diabetes medication, has demonstrated a reduction in renal function decline among patients with chronic kidney disease, regardless of their diabetes status. However, all previous studies excluded dialysis patients. Patients starting dialysis may still produce a certain amount of urine. Importantly, patients with better preserved residual kidney function tend to have better control of blood pressure and volume status, improved nutrition status, higher quality of life and reduced mortality rate.
The purpose of this study is to learn about the safety of empagliflozin in patients on peritoneal dialysis, in preparation for a future large clinical trial. Participants who newly initiate peritoneal dialysis will be randomly allocated to either empagliflozin on top of standard of care, or standard of care alone. Over a follow-up period of six months, the investigators will collect information on urine volume, blood pressure and glucose control. Safety, tolerability and drug compliance of empagliflozin will also be evaluated. If empagliflozin is found to be safe and well tolerated in patients on peritoneal dialysis, further large-scale randomized controlled trial may be conducted to evaluate its impact on residual kidney function and other relevant clinical outcomes.
详细描述
Diabetes is the leading cause of end stage kidney disease in developed countries. Peritoneal dialysis (PD) is a home-based and cost-effective modality of kidney placement therapy. Maintenance of residual kidney function (RKF) is one of the most crucial objectives to improve outcomes of PD patients. Observational studies showed that residual urine volume or residual glomerular filtration rate (GFR), but not peritoneal creatinine clearance, independently predicted patient survival. This benefit is likely attributed to better volume control, improved nutritional status, preserved endocrine function and enhanced clearance of uremic toxins in the presence of RKF. However, current therapeutic strategies to preserve RKF were most limited to the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and biocompatible PD solutions.
Hong Kong adopted the 'PD-first' policy since 1985, and has the highest proportion of PD patients in the world. Inadequate dialysis, which is directly related to the loss of RKF, is the second most common reason for a permanent transfer to hemodialysis among PD patients. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been shown to reduce albuminuria and delay progression of chronic kidney disease even in patients with advanced stages of kidney disease. It is postulated that the renoprotective effect of SGLT-2 inhibitors may be extended to dialysis population since a considerable proportion of patients still have urine output. SGLT2 inhibitors may potentially attenuate GFR decline in PD patients because heavy proteinuria independently predicted decline in residual GFR and onset of anuria. Moreover, preclinical studies suggested that empagliflozin reduced inflammation and oxidative stress by decreasing proinflammatory cytokines, inducing expression of anti-inflammatory M2 phenotype of macrophages, and antagonizing the effect of advanced glycation products. This beneficial effect may be particularly relevant to PD patients, where subclinical inflammation is common and inversely correlated with RKF.
Despite the potential promising effect of SGLT2-inhibitors in RKF in PD patients, dialysis patients were excluded in previous randomized controlled trials. In the present study, the investigators hypothesize that oral empagliflozin in addition to RAAS inhibitor, compared to RAAS inhibitor alone, better preserves RKF in patients newly started on PD. After a run-in period of 6 to 8 weeks where the dose of RAAS inhibitors are uptitrated to maximally tolerated dose, 48 incident PD patients will be randomized to empagliflozin or control (no empagliflozin) for a total of 6 months. This study aims to explore the feasibility of conducting a full-scale, adequately powered randomized controlled trial that investigates the effect of empagliflozin on RKF in incident PD patients.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Incident PD patients within 90 days of Tenckhoff catheter insertion
- •Age 18-75 years old
- •Patient with or without history of Type 2 diabetes
- •Residual GFR (defined as the average of 24-hour urinary urea and creatinine clearances) > 2ml/min/1.73m2 AND urine volume > 400ml per day
- •Patients who are willing to provide written informed consent
排除标准
- •Patients with history of hemodialysis (≥ 3 months) or renal transplant
- •Life expectancy <6 months
- •Prior use of any type of SGLT2 inhibitors within 1 month before screening visit
- •Poorly controlled diabetes with HBA1c >11%
- •Type 1 diabetes
- •History of any active malignancy within 5 years (except curatively resected basal cell or squamous cell skin cancers)
- •Peritonitis within 4 weeks
- •Ketoacidosis within 5 years
- •Known hypersensitivity to empagliflozin or other SGLT2 inhibitors
- •Any active acute or chronic physical or mental conditions that, in the opinion of the investigator, might interfere with the compliance of participants to or the performance of this study
- •Participation in any clinical trial or use of any investigational medicinal product 1 month before screening visit
研究组 & 干预措施
Intervention group
Patients randomized to intervention group will receive oral empagliflozin 10mg daily on top of optimized dose of RAAS inhibitor for 6 months
干预措施: Empagliflozin 10 MG (Drug)
结局指标
主要结局
Medication adherence
时间窗: 6 months
Proportion of prescribed empagliflozin that are taken by the patients (pill counting will be done by investigators at each follow up)
Recruitment rate
时间窗: During randomization
Number of patients who are randomized each month following the run-in period
Retention rate
时间窗: 6 months
Proportion of patients who have completed the whole study among patients that are randomized
次要结局
- Slope of residual GFR(6 months)
- Time to anuria(6 months)
- Difference in volume of overhydration(Month 0, 2, 4, 6)
- Incidence of lower limb amputation(6 months)
- Difference in systolic blood pressure(Month 0, 2, 4, 6)
- Incidence of ketoacidosis(6 months)
- Difference in residual urine volume(Month 0, 2, 4, 6)
- Difference in plasma N-terminal pro-brain type natriuretic peptide(Month 0, 2, 4, 6)
- Difference in volume of ultrafiltration per day(Month 0, 1, 2, 4, 6)
- Incidence of urinary tract infection(6 months)
- Incidence of genital tract infection(6 months)
- Incidence of severe hypoglycemia(6 months)
研究者
Cheuk-Chun SZETO
Professor
Chinese University of Hong Kong