A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease

Phase 3

Completed

• Conditions: Chronic Kidney Disease
• Interventions: Drug: Placebo; Drug: Dapagliflozin

• Registration Number: NCT03036150
• Lead Sponsor: AstraZeneca

Brief Summary

The purpose of this study is to evaluate the effect of dapagliflozin on renal outcomes and cardiovascular mortality in patients with chronic kidney disease.

Detailed Description

This is an international, multicentre, event-driven, randomized, double-blind, parallel group, placebo-controlled study, evaluating the effect of dapagliflozin versus placebo, given once daily in addition to standard of care, to prevent the progression of chronic kidney disease (CKD) or cardiovascular (CV)/renal death.

Study Timeline

• Study First Submitted: 2017-01-26
• Study First Submitted QC: 2017-01-26
• Study First Posted: 2017-01-30
• Study Start: 2017-02-02
• Primary Completion: 2020-06-12
• Study Completion: 2020-06-12
• Results First Submitted: 2021-04-19
• Status Verified: 2021-06
• Results First Submitted QC: 2021-06-15
• Last Update Submitted: 2021-06-15
• Results First Posted: 2021-07-07
• Last Update Posted: 2021-07-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 4304

Inclusion Criteria

• Provision of signed informed consent prior to any study specific procedures
• Female or male aged ≥18 years at the time of consent
• eGFR ≥25 and ≤75 mL/min/1.73m2 (CKD-EPI Formula) at visit 1
• Evidence of increased albuminuria 3 months or more before visit 1 and UACR ≥200 and ≤5000 mg/g at visit 1
• Stable, and for the patient maximum tolerated labelled daily dose, treatment with ACE-I or ARB for at least 4 weeks before visit 1, if not medically contraindicated,

Exclusion Criteria

• Autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis or ANCA-associated vasculitis
• Receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment
• History of organ transplantation
• Receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
• Type 1 diabetes mellitus
• New York Heart Association (NYHA) class IV Congestive Heart Failure at the time of enrolment
• MI, unstable angina, stroke or transient ischemic attack within 12 weeks prior to enrolment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo matching dapagliflozin.
Dapagliflozin	Dapagliflozin	Patients will be randomized 1:1 to either dapagliflozin or placebo.

Primary Outcome Measures

Name	Time	Method
Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD or CV Death or Renal Death.	Up to 38.2 months	End Stage Renal Disease (ESRD) is defined as: * Sustained eGFR \<15 mL/min/1.73m2 or,; * Chronic dialysis treatment or,; * Receiving a renal transplant The proportional hazards Cox regression model takes into account the time to the event. Data is reported as the numbers of subjects with the event and the Hazard ratio is included in the Statistical Analysis section attached to the Outcome Measure data table.

Secondary Outcome Measures

Name	Time	Method
Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD or Renal Death.	Up to 38.2 months	End Stage Renal Disease (ESRD) is defined as: * Sustained eGFR \<15 mL/min/1.73m2 or,; * Chronic dialysis treatment or,; * Receiving a renal transplant The proportional hazards Cox regression model takes into account the time to the event. Data is reported as the numbers of subjects with the event and the Hazard ratio is included in the Statistical Analysis section attached to the Outcome Measure data table.
Time to the First Occurrence of Either of the Components of the Composite: CV Death or Hospitalization for Heart Failure.	Up to 38.2 months	The proportional hazards Cox regression model takes into account the time to the event. Data is reported as the numbers of subjects with the event and the Hazard ratio is included in the Statistical Analysis section attached to the Outcome Measure data table.
Time to Death From Any Cause.	Up to 38.2 months	The proportional hazards Cox regression model takes into account the time to the event. Data is reported as the numbers of subjects with the event and the Hazard ratio is included in the Statistical Analysis section attached to the Outcome Measure data table.

Trial Locations

Locations (1)

Research Site; 🇻🇳 Hochiminh, Vietnam