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

June 12, 2025 updated by: Children's Hospital of Fudan University

The Efficacy and Safety of Dapagliflozin in the Treatment of Hereditary Kidney Disease With Proteinuria in Children: a Prospective, Randomized Crossover Trial

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

44

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 201102
        • Recruiting
        • Children's Hospital of Fudan University
        • Contact:
        • Principal Investigator:
          • YIHUI ZHAI
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: 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: 5 mg/day for participants ≤30 kg; 5 mg/day initially (first week), then increased to 10 mg/day for participants >30 kg 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 maintenance RAASi therapy while discontinuing dapagliflozin.

③Standard Treatment alone for an additional 12 weeks. To ensure compliance, all participants are required to complete a daily medication log.If any adverse events (AEs) occur, appropriate clinical interventions will be promptly implemented
Experimental: 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.
Drug: Standard Treatment alone for 12 weeks ,washout period for 4 weeks ,then Dapagliflozin+Standard Treatment for 12 weeks

①Standard 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.)

②Washout period for 4 weeks Participants should maintenance RAASi therapy while discontinuing dapagliflozin.

③Dapagliflozin+Standard Treatment for 12 weeks Dapagliflozin therapy (Farxiga®, 10 mg tablets) is administered orally once daily,with dose adjustment based on body weight: 5 mg/day for participants ≤30 kg; 5 mg/day initially (first week), then increased to 10 mg/day for participants >30 kg.This combined therapy will be administered for 12 weeks To ensure compliance, all participants are required to complete a daily medication log.If any adverse events (AEs) occur, appropriate clinical interventions will be promptly implemented

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in 24-hour urinary protein excretion from baseline to week 12
Time Frame: 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.
From baseline to week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in urinary protein to creatinine ratio (UPCR) levels from baseline to week 12
Time Frame: 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).
From baseline to week 12
Changes in urinary albumin to creatinine ratio (UACR) levels from baseline to week 12
Time Frame: 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).
From baseline to week 12
Changes in serum albumin levels from baseline to week 12
Time Frame: 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.
From baseline to week 12
Changes in estimated glomerular filtration rate from baseline to week 12
Time Frame: 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).
From baseline to week 12
Changes in weight from baseline to week 12
Time Frame: 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.
From baseline to week 12
Changes in blood pressure from baseline to week 12
Time Frame: 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.
From baseline to week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital of Fudan University

Collaborators

The Second Hospital of Hebei Medical University
First Affiliated Hospital, Sun Yat-Sen University
Shandong Provincial Hospital
Second Affiliated Hospital of Wenzhou Medical University
The First Affiliated Hospital of Henan University of Traditional Chinese Medicine
Kunming Children's Hospital
Guangzhou Women and Children's Medical Center
The Children's Hospital of Zhejiang University School of Medicine
Zhengzhou Children's Hospital, China
Xian Children's Hospital
Children's Hospital of Nanjing Medical University
Wuhan Children's Hospital
Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region
Children's Hospital of The Capital Institute of Pediatrics
Xuzhou Children Hospital
Wuxi Women's & Children's Hospital
Guiyang Maternity and Child Health Care Hospital
Xiamen Women's and Children's Hospital
Maternal and Child Health Care Hospital of Hainan Province
First People's Hospital of Urumqi

Investigators

  • Study Director: YIHUI ZHAI, Children's Hospital of Fudan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 22, 2025

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

March 31, 2027

Study Registration Dates

First Submitted

March 17, 2025

First Submitted That Met QC Criteria

March 17, 2025

First Posted (Actual)

March 21, 2025

Study Record Updates

Last Update Posted (Actual)

June 15, 2025

Last Update Submitted That Met QC Criteria

June 12, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DAPA-PedHKD

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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