Phase 3 SGLT2 inhibitor renal outcomes trial stopped early due to positive efficacy findings

News - July 17, 2018

The Phase 3 CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) clinical trial, evaluating the efficacy and safety of canagliflozin versus placebo, used in addition to standard of care for patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), is being stopped early based on the achievement of pre-specified efficacy criteria.

The decision is based on a recommendation from the study’s Independent Data Monitoring Committee (IDMC), formulated during a planned interim analysis. This recommendation was based on demonstration of efficacy, as the trial had achieved pre-specified criteria for the primary composite endpoint of end-stage kidney disease (time to dialysis or kidney transplantation), doubling of serum creatinine, and renal or cardiovascular (CV) death, when canagliflozin was used in addition to standard of care.

Canagliflozin is an SGLT2 inhibitor, used along with diet and exercise to lower blood sugar in adults with T2DM. CREDENCE is the first dedicated renal outcomes trial of treatment with canagliflozin in patients with CKD and T2D on the background of standard of care, including ACE inhibitors and ARBs. This randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial evaluates the efficacy and safety of canagliflozin versus placebo in preventing clinically important renal and CV outcomes in patients with T2D and established kidney disease. The trial enrolled approximately 4,400 patients with T2D, with eGFR ≥30 to <90 mL/min/1.73 m², and albuminuria (urinary albumin: creatinine ratio >300 to ≤5,000 mg/g). All patients were required to be on the maximum labeled or tolerated dose of an ACE inhibitor or ARB for more than four weeks prior to randomization.

According to the paper by Jardine et al. on the rationale and design of the CREDENCE study, with a planned recruitment of at least 4,200 patients, it will have 90% power to detect a 20% relative risk reduction in the primary renal endpoint based on events being observed in 844 patients, and a 2-sided P-value of 0.05. A 20% relative risk reduction is considered to be a clinically meaningful effect commensurate with the risk reductions seen in studies of agents targeting the renin-angiotensin-aldosterone system.

At this time, canagliflozin is contraindicated for patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m²), end-stage renal disease (ESRD), or patients on dialysis. In addition, canagliflozin is not recommended when eGFR is persistently less than 45 mL/min/1.73 m². It should not be used in type 1 diabetes or in patients with diabetic ketoacidosis.

Source: Press release The Janssen Pharmaceutical Companies of Johnson & Johnson, July 16, 2018

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