Efficacy and Safety of Dapagliflozin in Children With Proteinuric Chronic Kidney Disease

Study Overview
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Brief Summary
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We aim to investigate the antiproteinuric effect of adding Dapagliflozin to the standard of care in children with proteinuria.

Detailed Description
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Blockers of renin angiotensin aldosterone system (RAAS) such as angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) are considered the standard of care in treatment of Proteinuric Chronic Kidney Disease. However, these agents lead to incomplete renal protection. The purpose of the study is to investigate the antiproteinuric effect of adding Dapagliflozin to the standard of care in children with proteinuria. In this study, participants were randomly assigned (1:1) to receive ACEI+Dapagliflozin (5mg or 10mg, based on body weight) or ACEI only once daily for 24 weeks. Prespecified outcomes includes changes in 24-hr proteinuria, albumin, eGFR (estimated glomerular filtration rate), blood pressure, body weight and so on.

Official Title
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Efficacy and Safety of Dapagliflozin in Children With Proteinuric Chronic Kidney Disease : a Prospective, Randomized, Placebo-controlled Trial

Conditions
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Proteinuria, Chronic Kidney Diseases

Intervention / Treatment
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* Drug: ACEI treatment
* Drug: Dapagliflozin+ACEI treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 6 years to 18 years； Urinary protein excretion > 200 mg in a 24-hr urine collection； Without any immunosuppressant medications such as corticosteroids, CNIs and so on； Estimated GFR ≥ 60 ml/min/1.73m2（estimated with Schwartz formula）； No history of diabetes； On stable doses of ACE inhibitors or angiotensin receptor blockers (ARBs) for > 1 month； Willing to sign informed consent. Exclusion Criteria: Autosomal dominant polycystic kidney disease or autosomal recessive polycystic kidney disease, lupus nephritis, or ANCA-associated vasculitis; Blood pressure less than 5th percentile of the same gender, age, and height; Uncontrolled urinary tract infection at screening; At risk for dehydration or volume depletion; Evidence of hepatic disease: an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) two times the upper limit of normal History of organ transplantation, cancer, liver disease; Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications including, but not limited to any of the following: History of active inflammatory bowel disease within the last six months; Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection; Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months; Pancreatic injury or pancreatitis within the last six months; Participation in another therapeutic trial with an investigational drug within 30 days prior to informed consent; History of noncompliance to medical regimens or unwillingness to comply with the study protocol.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: ACEI treatment<br>Drug: ACEI will be given once daily | Drug: ACEI treatment<br>* ACEI, will be given once daily based on body weight (0.2mg/kg/d-0.6mg/kg/d，max 20mg/d), for 24 weeks<br>* Other names: Control group;|
| Experimental: Dapagliflozin+ACEI treatment<br>Drug: ACEI, will be given once daily Drug: Dapagliflozin, will be given once daily | Drug: Dapagliflozin+ACEI treatment<br>* Dapagliflozin will be given 10 mg/day (weight>30kg) or 5mg/day (weight≤30kg), for 24 weeks ACEI, will be given based on body weight (max 20mg/d), for 24 weeks.<br>* Other names: Treatment group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in 24 hour proteinuria | Urine will be collected for 24 hours and total urinary albumin excretion will be measured | From baseline to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in 24 hour proteinuria | Urine will be collected for 24 hours and total urinary albumin excretion will be measured | From baseline to week 24 | 
| The change in albumin from baseline to week 24 | Serum albumin levels are repeated measurement data | Measured at baseline, weeks 4, weeks 8, weeks 12, weeks 24 | 
| The change in eGFR (estimated glomerular filtration rate) from baseline to week 24 | eGFR will be evaluated using Schwartz formula (eGFR=k*height(cm)/serum creatinine(umol/L)), k=36.5), and eGFR are repeated measurement data | Measured at baseline, weeks 4, weeks 8, weeks 12, weeks 24 | 
| The change blood pressure from baseline to week 24 | Blood pressure including systolic blood pressure (SBP) and diastolic blood pressure (DBP) are repeated measurement data | Measured at baseline, weeks 4, weeks 8, weeks 12, weeks 24 | 
| The change in body weight from baseline to week 24 | Body weight are repeated measurement data and will be measured in the morning | Measured at baseline, weeks 4, weeks 8, weeks 12, weeks 24 | 
| The number of hypoglycemia episodes during the treatment | Patients will be asked to measure fasting blood glucose every morning and record the data by their parents during the treatment period. Hypoglycemia is defined as glucose level less than 3.9mmol/L. | From baseline to week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Angiotensin Converting Enzyme Inhibitors, Sodium-glucose co-transporter 2 inhibitors, Dapagliflozin