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

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

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

Study Overview

• Status: Withdrawn
• Conditions: Chronic Kidney Diseases; Proteinuria
• Intervention / Treatment: Drug: ACEI treatment; Drug: Dapagliflozin+ACEI treatment

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 Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201102
      • Children's Hospital of Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: ACEI treatment; Drug: ACEI will be given once daily	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; Other Names: Control group
Experimental: Dapagliflozin+ACEI treatment; Drug: ACEI, will be given once daily Drug: Dapagliflozin, will be given once daily	Drug: 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.; Other Names: Treatment group

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University
• Investigators: Study Director: Qian Shen, Profressor, Children's Hospital of Fudan University

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2021
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: August 26, 2020
• First Submitted That Met QC Criteria: August 26, 2020
• First Posted (Actual): August 28, 2020

Study Record Updates

• Last Update Posted (Actual): December 29, 2020
• Last Update Submitted That Met QC Criteria: December 24, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Dapagliflozin; Angiotensin Converting Enzyme Inhibitors; Sodium-glucose co-transporter 2 inhibitors
• Additional Relevant MeSH Terms: Urologic Diseases; Urological Manifestations; Renal Insufficiency; Urination Disorders; Kidney Diseases; Renal Insufficiency, Chronic; Proteinuria; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin; Angiotensin-Converting Enzyme Inhibitors
• Other Study ID Numbers: EASOD.01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No