Clinical trial NCT04531397: Efficacy and Safety of Dapagliflozin in Children With Proteinuric Chronic Kidney Disease
Official title: Efficacy and Safety of Dapagliflozin in Children With Proteinuric Chronic Kidney Disease : a Prospective, Randomized, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Proteinuria
Chronic Kidney Diseases
Keywords: Angiotensin Converting Enzyme Inhibitors
Sodium-glucose co-transporter 2 inhibitors
Dapagliflozin
Lead sponsor: Children's Hospital of Fudan University
Sponsor class: OTHER
First posted: 2020-08-28
Enrollment: 0
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The change in 24 hour proteinuria
timeFrame: From baseline to week 12
Secondary outcomes:
measure: The change in 24 hour proteinuria
timeFrame: From baseline to week 24
measure: The change in albumin from baseline to week 24
timeFrame: Measured at baseline, weeks 4, weeks 8, weeks 12, weeks 24
measure: The change in eGFR (estimated glomerular filtration rate) from baseline to week 24
timeFrame: Measured at baseline, weeks 4, weeks 8, weeks 12, weeks 24
measure: The change blood pressure from baseline to week 24
timeFrame: Measured at baseline, weeks 4, weeks 8, weeks 12, weeks 24
measure: The change in body weight from baseline to week 24
timeFrame: Measured at baseline, weeks 4, weeks 8, weeks 12, weeks 24
measure: The number of hypoglycemia episodes during the treatment
timeFrame: From baseline to week 24
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
state: Shanghai
Study officials:
affiliation: Children's Hospital of Fudan University
name: Qian Shen, Profressor
role: STUDY_DIRECTOR
References: