Dapagliflozin and Renal Surrogate Outcomes in Advanced Chronic Kidney Disease

NCT05196347 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: ESR-21-21200 V1.4
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

This is an investigator-led, randomized, open-label, blinded-endpoint, multicenter study that will include a total of approximately 180 subjects from 2 sites. Subjects with an estimated glomerular filtration rate (eGFR) of 10 to 30 mL/min/1.73m2 will be included. The goal of this study is to assess the efficacy and safety of dapagliflozin (Forxiga®, AstraZeneca) in reducing renal function progression and complications of chronic kidney disease (CKD) in patients with CKD stage 4 and 5 under the integrated CKD care. Subjects will be allocated to integrated CKD care program + dapagliflozin or integrated CKD care program alone. The primary endpoint is eGFR decline after randomization between 2 arms. The secondary endpoints are renal and cardiovascular composite outcomes.

Conditions

Chronic Kidney Diseases

Outcome Measures

Primary Outcomes (1)

• eGFR slope

  eGFR decline after randomization between 2 arms

  from randomization to renal replacement therap, study completion or censoring event, upto 96 weeks

Secondary Outcomes (3)

• Renal composite outcome

  from randomization to study completion or censoring event, upto 96 weeks

• Renal and heart failure composite outcome

  from randomization to study completion or censoring event, upto 96 weeks

• Renal and cardiovascular composite outcome

  from randomization to study completion or censoring event, upto 96 weeks

Study Arms (2)

dapagliflozin + integrated CKD care program

EXPERIMENTAL

Subjects will be received dapagliflozin 5 mg for 4 weeks. Uptitration to 10 mg will be done between 5 to 12th weeks, if eGFR dip \<20%. In both arms, the integrated CKD care program includes CKD stage 4 and 5 education, diet counseling, bioimpedance and echocardiography measurements to control overhydration at 0-1 liter (by body composition monitor (BCM; Fresenius))

Drug: Dapagliflozin

integrated CKD care program

ACTIVE COMPARATOR

In both arms, the integrated CKD care program includes CKD stage 4 and 5 education, diet counseling, bioimpedance and echocardiography measurements to control overhydration at 0-1 liter (by body composition monitor (BCM; Fresenius))

Drug: Dapagliflozin

Interventions

Dapagliflozin DRUG

In dapagliflozin arm, subjects will be received dapagliflozin 5 mg for 4 weeks. Uptitration to 10 mg will be done between 5 to 12th weeks, if eGFR dip \<20%.

Also known as: Integrated CKD care program

dapagliflozin + integrated CKD care program; integrated CKD care program

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures.
• Aged ≥20 years at the time of consent.
• eGFR ≥10 and ≤30 mL/min/1.73m2 (Modification of Diet in Renal Disease (MDRD) equation ) at randomization.
• eGFR decline ≥2.5 mL/min/1.73m2 (≥ 3 measurements, simple linear regression) in one year before randomization.
• In the pre-ESRD care and education program of Ministry of Health and Welfare of Taiwan (pre-ESRD program) for ≥3 months before randomization.

You may not qualify if:

• Lupus nephritis, anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis and organ transplantation.
• Receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor.
• Any condition outside the renal and CV disease area, with a life expectancy of less than 2 years based on investigator's clinical judgement.
• Active malignancy requiring treatment at the time of visit 1.
• Women of child-bearing potential who are not willing to use a medically accepted method of contraception throughout the study, OR women who have a positive pregnancy test at enrolment OR women who are breast-feeding.
• Urinary tract obstruction (hydronephrosis, hydroureter and abnormal post-voiding residual urine volume under renal echography).
• Frequent urosepsis (≥2 times in one year before enrollment) and history of Fournier's gangrene.
• Inability of the patient, in the opinion of the investigator, to understand and/or comply with treatment, procedures and/or follow-up OR any conditions that, in the opinion of the investigator, may render the patient unable to complete the study.

Sponsors & Collaborators

• Kaohsiung Medical University: lead

Study Sites (1)

Chi-Chih Hung

Kaohsiung City, Taiwan

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Chi-Chih Hung, MD

  Kaohsiung Medical University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: To determine if dapagliflozin + integrated CKD care program is more effective in reducing renal function progression than integrated CKD care program

Study Record Dates

• First Submitted: December 21, 2021
• First Posted: January 19, 2022
• Study Start: May 27, 2022
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2024
• Last Updated: March 13, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)