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

NCT06890143 | Recruiting Phase 3

• 1 other identifier: DAPA-PedHKD
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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

Conditions

Pediatric Hereditary Kidney Diseases

Keywords

hereditary kidney diseases; proteinuria; dapagliflozin; children

Outcome Measures

Primary Outcomes (1)

• Changes in 24-hour urinary protein excretion 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 Outcomes (6)

• 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 blood pressure from baseline to week 12

  From baseline to week 12

Study Arms (2)

Early Dapagliflozin Group

EXPERIMENTAL

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

Delayed Dapagliflozin Group

EXPERIMENTAL

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

Interventions

Dapagliflozin+Standard Treatment for 12 weeks,washout period for 4 weeks，then Standard Treatment alone for12 weeks DRUG

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

Early Dapagliflozin Group

Standard Treatment alone for 12 weeks ,washout period for 4 weeks ,then Dapagliflozin+Standard Treatment for 12 weeks DRUG

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

Delayed Dapagliflozin Group

Eligibility Criteria

• Age: 6 Years - 18 Years
• Gender Eligibility Details: gender based.
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, 201102, China

RECRUITING

Related Publications (30)

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• The Expert Group of Chinese Expert Consensus on the Clinical Application of Sodium-glucose Cotransporter 2 Inhibitors in Patients with Chronic Kidney Disease. Chinese expert consensus on the clinical application of sodium-glucose cotransporter 2 inhibitors in patients with chronic kidney disease. Chin Med J (Engl). 2024 Jun 5;137(11):1264-1266. doi: 10.1097/CM9.0000000000003145. Epub 2024 May 13. No abstract available.

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• Koppe L, Fouque D. The Role for Protein Restriction in Addition to Renin-Angiotensin-Aldosterone System Inhibitors in the Management of CKD. Am J Kidney Dis. 2019 Feb;73(2):248-257. doi: 10.1053/j.ajkd.2018.06.016. Epub 2018 Aug 24.

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• Zhang W, Dou Y, Liu J, Liu T, Yan W, Shen Q, Xu H, Zhai Y. Effects and safety of dapagliflozin in paediatric hereditary kidney disease: protocol for a multicentric, prospective, open and randomised crossover study (DAPA-PedHKD). BMJ Open. 2025 Dec 14;15(12):e109833. doi: 10.1136/bmjopen-2025-109833.

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MeSH Terms

Conditions

Proteinuria

Condition Hierarchy (Ancestors)

Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• YIHUI ZHAI

  Children's Hospital of Fudan University

  STUDY DIRECTOR

Central Study Contacts

YIHUI ZHAI

CONTACT

+86-021-64932827; yhzhai@fudan.edu.cn

WEI ZHANG

CONTACT

+86-021-64932827; zhangw421489@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2025
• First Posted: March 21, 2025
• Study Start: March 22, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: June 15, 2025

Record last verified: 2025-06

Locations

CN (1)