Pediatric Hereditary Kidney Diseases
Conditions
Keywords
hereditary kidney diseases, proteinuria, dapagliflozin, children
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.
Interventions
DRUGDapagliflozin+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
DRUGStandard 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
Sponsors
Children's Hospital of Fudan University
Guangzhou Women and Children's Medical Center
Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region
Shandong Provincial Hospital
The First Affiliated Hospital of Henan University of Traditional Chinese Medicine
Wuhan Children's Hospital
Xuzhou Children Hospital
First Affiliated Hospital, Sun Yat-Sen University
Kunming Children's Hospital
The Children's Hospital of Zhejiang University School of Medicine
Children's Hospital of Nanjing Medical University
Zhengzhou Children's Hospital, China
Xiamen Women's and Children's Hospital
Guiyang Maternity and Child Health Care Hospital
Maternal and Child Health Care Hospital of Hainan Province
Children's Hospital of The Capital Institute of Pediatrics
Second Affiliated Hospital of Wenzhou Medical University
Xian Children's Hospital
The Second Hospital of Hebei Medical University
Wuxi Women's & Children's Hospital
First People's Hospital of Urumqi
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
China
Contacts
CONTACTYIHUI ZHAI
CONTACTWEI ZHANG
STUDY_DIRECTORYIHUI ZHAI
Children's Hospital of Fudan University
Outcome results
None listed