The Efficacy and Safety of Dapagliflozin in the Treatment of Hereditary Kidney Disease With Proteinuria in Children: a Prospective, Randomized Crossover Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Changes in 24-hour urinary protein excretion from baseline to week 12
研究概览
简要总结
This study is a multicenter, randomized controlled crossover trial aimed to evaluate the efficacy and safety of dapagliflozin in the treatment of hereditary kidney disease with proteinuria in children
详细描述
Chronic kidney disease (CKD) poses a significant public health threat to children, with hereditary kidney diseases exhibiting limited therapeutic efficacy in reducing proteinuria. Global studies have demonstrated that dapagliflozin significantly reduces proteinuria in adults with CKD; however, its role in pediatric hereditary kidney diseases lacks strong evidence .This study aims to investigate the efficacy and safety of dapagliflozin in children with proteinuric hereditary kidney diseases.
This is a multicenter, open-label, block-randomized, crossover clinical trial with 1:1 allocation. A total of 44 participants will be enrolled to compare the efficacy and safety of dapagliflozin combined with standard renin-angiotensin-aldosterone system inhibitor (RAASi) therapy versus RAASi therapy alone.
The primary endpoint is the change in 24-hour urinary protein levels from baseline to 12 weeks of treatment. Secondary endpoints include: urinary protein-to-creatinine ratio (UPCR), urinary albumin-to-creatinine ratio (UACR), serum albumin levels, estimated glomerular filtration rate (eGFR), blood pressure changes, and body weight changes.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of hereditary kidney disease (identification of pathogenic genes through molecular genetic testing; for Alport syndrome, molecular diagnosis is not necessarily required if diagnosed based on clinical and pathological findings; for those with a clear family history and a high clinical suspicion of hereditary kidney disease).
- •24 - hour urinary protein level > 0.2 g or urinary protein to creatinine ratio (UPCR) > 0.2 mg/mg.
- •Calculate the estimated glomerular filtration rate (eGFR) using the Schwartz formula (36.5 * height in cm / serum creatinine in μmol/L), with eGFR ≥ 60 ml/min/1.73 m².
- •Stable use of the basic treatment drug RAASi (including ACEI/ARB) for more than 4 weeks, and no dosage adjustment during the treatment period.
- •Willingness to sign the informed consent form.
排除标准
- •Exclusion applies if any of the following criteria are met:
- •Treatment with hormones/immunosuppressive agents within the previous 4 weeks.
- •Treatment with SGLT2 inhibitors within the previous 4 weeks.
- •Comorbid diabetes.
- •Uncontrolled urinary tract infection.
- •Evidence of urinary tract obstruction such as dysuria.
- •Blood pressure below the 5th percentile for the same gender, age, and height.
- •Organ transplantation.
- •Presence of any of the following definite evidence of liver disease: ALT/AST reaching 2 times the normal value, hepatic encephalopathy, esophageal varices, or portal shunt surgery.
- •Comorbid medical conditions that may affect drug absorption, distribution, metabolism, and excretion, including but not limited to any of the following: active inflammatory bowel disease within the past 6 months, history of major gastrointestinal surgery (such as gastrectomy, gastroenterostomy, intestinal resection), gastrointestinal ulcer, gastrointestinal or rectal bleeding within the past 6 months, pancreatic injury or pancreatitis within the past 6 months.
- •Subjects at risk of dehydration or volume depletion, which may affect drug efficacy or safety.
- •Participation in other drug trials within the previous 4 weeks.
- •Blood loss exceeding 400 ml within the previous 8 weeks.
- •Poor past medication compliance or unwillingness to complete the trial.
- •Any other medical conditions that may place the patient at a higher risk due to participation in this study.
研究组 & 干预措施
Early Dapagliflozin Group
①Dapagliflozin+Standard Treatment for 12 weeks. Dapagliflozin therapy (Farxiga®, 10 mg tablets) is administered orally once daily,with dose adjustment based on body weight.Standard Treatment:standard renin-angiotensin-aldosterone system inhibitor (RAASi) therapy(The dosage will be maintained at the pre-enrollment level throughout the entire treatment period, with no adjustments made during therapy.),This combined therapy will be administered for 12 weeks.
② Washout period for 4 weeks Participants should maintain RAASi therapy while discontinuing dapagliflozin.
③RAASi monotherapy alone for an additional 12 weeks.
干预措施: Dapagliflozin+Standard Treatment for 12 weeks,washout period for 4 weeks，then Standard Treatment alone for12 weeks (Drug)
Delayed Dapagliflozin Group
① Standard Treatment for 12 weeks Standard Treatment:Standard renin-angiotensin-aldosterone system inhibitor (RAASi) therapy alone for 12 weeks.(The dosage will be maintained at the pre-enrollment level throughout the entire treatment period, with no adjustments made during therapy.)
② Washout period for 4 weeks Participants should maintain RAASi therapy without additional interventions.
③ Dapagliflozin+Standard Treatment for 12 weeks Dapagliflozin therapy is administered orally once daily,with dose adjustment based on body weight.This combined therapy will be administered for 12 weeks.
干预措施: Standard Treatment alone for 12 weeks ,washout period for 4 weeks ,then Dapagliflozin+Standard Treatment for 12 weeks (Drug)
结局指标
主要结局
Changes in 24-hour urinary protein excretion from baseline to week 12
时间窗: From baseline to week 12
The change in 24-hour urinary protein excretion from baseline to week 12 of treatment with dapagliflozin combined with RAASi . According to the research protocol, the 24-hour urine of the pediatric patients is collected during the planned follow-up period, and the pyrogallol red method is used for the quantitative test of the protein in the urine.
次要结局
- Changes in urinary protein to creatinine ratio (UPCR) levels from baseline to week 12(From baseline to week 12)
- Changes in urinary albumin to creatinine ratio (UACR) levels from baseline to week 12(From baseline to week 12)
- Changes in serum albumin levels from baseline to week 12(From baseline to week 12)
- Changes in estimated glomerular filtration rate from baseline to week 12(From baseline to week 12)
- Changes in weight from baseline to week 12(From baseline to week 12)
- Changes in blood pressure from baseline to week 12(From baseline to week 12)