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

Chronic Kidney Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04531397
• Other study ID #: EASOD.01
• Status: Withdrawn
• Phase: Phase 4
• Start date: January 1, 2021
• Est. completion date: December 31, 2022

Study information

• Verified date: December 2020
• Source: Children's Hospital of Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 31, 2022
• Est. primary completion date: June 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Kidney Diseases
• Proteinuria
• Renal Insufficiency, Chronic

Intervention

Drug:
• ACEI treatment
ACEI, will be given once daily based on body weight (0.2mg/kg/d-0.6mg/kg/d,max 20mg/d), for 24 weeks
• Dapagliflozin+ACEI treatment
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.

Locations

Country	Name	City	State
China	Children's Hospital of Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital of Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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