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

Phase 4

Withdrawn

• Conditions: Chronic Kidney Diseases; Proteinuria
• Interventions: Drug: ACEI treatment; Drug: Dapagliflozin+ACEI treatment

• Registration Number: NCT04531397
• Lead Sponsor: Children's Hospital of Fudan University

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2020-08-26
• Study First Submitted QC: 2020-08-26
• Study First Posted: 2020-08-28
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-24
• Last Update Posted: 2020-12-29
• Study Start: 2021-01-01
• Primary Completion: 2022-06-01
• Study Completion: 2022-12-31

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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:

  1. History of active inflammatory bowel disease within the last six months;
  2. Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
  3. Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months;
  4. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ACEI treatment	ACEI treatment	Drug: ACEI will be given once daily
Dapagliflozin+ACEI treatment	Dapagliflozin+ACEI treatment	Drug: ACEI, will be given once daily Drug: Dapagliflozin, will be given once daily

Primary Outcome Measures

Name	Time	Method
The change in 24 hour proteinuria	From baseline to week 12	Urine will be collected for 24 hours and total urinary albumin excretion will be measured

Secondary Outcome Measures

Name	Time	Method
The change in 24 hour proteinuria	From baseline to week 24	Urine will be collected for 24 hours and total urinary albumin excretion will be measured
The change in albumin from baseline to week 24	Measured at baseline, weeks 4, weeks 8, weeks 12, weeks 24	Serum albumin levels are repeated measurement data
The change in eGFR (estimated glomerular filtration rate) from baseline to week 24	Measured at baseline, weeks 4, weeks 8, weeks 12, weeks 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
The change blood pressure from baseline to week 24	Measured at baseline, weeks 4, weeks 8, weeks 12, weeks 24	Blood pressure including systolic blood pressure (SBP) and diastolic blood pressure (DBP) are repeated measurement data
The change in body weight from baseline to week 24	Measured at baseline, weeks 4, weeks 8, weeks 12, weeks 24	Body weight are repeated measurement data and will be measured in the morning
The number of hypoglycemia episodes during the treatment	From baseline to week 24	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.

Trial Locations

Locations (1)

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