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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin<br>Patients will be randomized 1:1 to either dapagliflozin or placebo. | Drug: Dapagliflozin<br>* 10 mg or 5 mg tablets given once daily, per oral use.<br>* Other names: Farxiga TM;|
| Placebo Comparator: Placebo<br>Placebo matching dapagliflozin. | Drug: Placebo<br>* Placebo matching dapagliflozin 10 mg or 5 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | Up to 38.2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD or Renal Death. | 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. | Up to 38.2 months | 
| Time to the First Occurrence of Either of the Components of the Composite: CV Death or Hospitalization for Heart Failure. | 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. | Up to 38.2 months | 
| Time to Death From Any Cause. | 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. | Up to 38.2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Kidney Disease (CKD), Cardiovascular Events (CV), Phase III outcome trial