The Efficacy and Safety of Dapagliflozin in the Treatment of Hereditary Kidney Disease With Proteinuria in Children

Phase 3

Recruiting

• Conditions: Pediatric Hereditary Kidney Diseases
• Interventions: Drug: Dapagliflozin+Standard Treatment for 12 weeks,washout period for 4 weeks，then Standard Treatment alone for12 weeks; Drug: Standard Treatment alone for 12 weeks ,washout period for 4 weeks ,then Dapagliflozin+Standard Treatment for 12 weeks

• Registration Number: NCT06890143
• Lead Sponsor: Children's Hospital of Fudan University

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2025-03-17
• Study First Submitted QC: 2025-03-17
• Study First Posted: 2025-03-21
• Study Start: 2025-03-22
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-12
• Last Update Posted: 2025-06-15
• Primary Completion: 2026-12-31
• Study Completion: 2027-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

• 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.

Exclusion Criteria

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.
• Tumor.
• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Early Dapagliflozin Group	Dapagliflozin+Standard Treatment for 12 weeks,washout period for 4 weeks，then Standard Treatment alone for12 weeks	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.
Delayed Dapagliflozin Group	Standard Treatment alone for 12 weeks ,washout period for 4 weeks ,then Dapagliflozin+Standard Treatment for 12 weeks	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.

Primary Outcome Measures

Name	Time	Method
Changes in 24-hour urinary protein excretion from baseline to week 12	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.

Secondary Outcome Measures

Name	Time	Method
Changes in urinary protein to creatinine ratio (UPCR) levels from baseline to week 12	From baseline to week 12	The change in the urinary protein to creatinine ratio (UPCR) levels from baseline to week 12 of treatment with dapagliflozin combined with RAASi. The pyrogallol red method is used for detecting urinary protein, and the enzymatic method is used for detecting urinary creatinine. UPCR = urinary protein/urinary creatinine (mg/mg).
Changes in urinary albumin to creatinine ratio (UACR) levels from baseline to week 12	From baseline to week 12	The change in urinary albumin to creatinine ratio (UACR) levels from baseline to week 12 of treatment with dapagliflozin combined with RAASi. The immunoturbidimetric method is used for detecting urinary albumin, and the enzymatic method is used for detecting urinary creatinine. UACR = urinary albumin/urinary creatinine (mg/g).
Changes in serum albumin levels from baseline to week 12	From baseline to week 12	The change in the serum albumin level from baseline to week 12 of treatment with dapagliflozin combined with RAASi. Venous blood is collected, and the test is conducted through the routine biochemical examination in the hospital.
Changes in estimated glomerular filtration rate from baseline to week 12	From baseline to week 12	The change in the estimated glomerular filtration rate (eGFR) from baseline to week 12 of treatment with dapagliflozin combined with RAASi. Venous blood is collected, and the serum creatinine level is detected through the routine biochemical examination in the hospital. The eGFR is calculated according to the Schwartz formula (36.5 \* height in cm / serum creatinine in μmol/L).
Changes in blood pressure from baseline to week 12	From baseline to week 12	The change in both systolic and diastolic blood pressure from baseline to week 12 of treatment with dapagliflozin combined with RAASi. The measurement is taken after the pediatric patient sits quietly for 5 minutes.
Changes in weight from baseline to week 12	From baseline to week 12	The change in body weight from baseline to week 12 of treatment with dapagliflozin combined with RAASi. The measurement is taken using a calibrated weighing scale.

Trial Locations

Locations (1)

Children's Hospital of Fudan University; 🇨🇳 Shanghai, Shanghai, China