Researchers running the EMPA-KIDNEY trial that’s been testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in about 6,600 patients with chronic kidney disease (CKD) announced on March 16 that they had stopped the trial early because of positive efficacy that met the study’s prespecified threshold for early termination.
EMPA-KIDNEY is the third major trial of an agent from the sodium-glucose cotransport 2 (SGLT2) inhibitor class tested in patients with CKD to be stopped early because of positive results that met a prespecified termination rule.
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In 2020, the DAPA-CKD trial of dapagliflozin (Farxiga) stopped early, after a median follow-up of 2.4 years, because of positive efficacy results. In 2019, the same thing happened in the CREDENCE trial of canagliflozin (Invokana), with the unexpected halt coming after a median follow-up of 2.62 years.
The announcement about EMPA-KIDNEY did not include information on median follow-up, but enrollment into the trial ran from May 2019 to April 2021, which means that the longest that enrolled patients could have been in the study was about 2.85 years.
The primary efficacy endpoint in EMPA-KIDNEY was a composite of a sustained decline in estimated glomerular filtration rate (eGFR) to less than 10 mL/min/1.73 m2, renal death, a sustained decline of at least 40% in eGFR from baseline, or cardiovascular death. The announcement of the trial’s early termination provided no details on the efficacy results.
EMPA-KIDNEY enrolled a wider range of patients
EMPA-KIDNEY expands the scope of types of patients with CKD now shown to benefit from treatment with an SGLT2 inhibitor. CREDENCE tested canagliflozin only in patients with type 2 diabetes and diabetic nephropathy, and in DAPA-CKD, two-thirds of enrolled patients had type 2 diabetes, and all had CKD. In EMPA-KIDNEY, 46% of the 6,609 enrolled patients had diabetes (including a very small number with type 1 diabetes).
Another departure from prior studies of an SGLT2 inhibitor for patients selected primarily for having CKD was that in EMPA-KIDNEY, 20% of patients did not have albuminuria, and for 34%, eGFR at entry was less than 30 mL/min/1.73 m2, with all enrolled patients required to have an eGFR at entry of greater than or equal to 20 mL/min/1.73 m2. Average eGFR in EMPA-KIDNEY was about 38 mL/min/1.73 m2. To be included in the trial, patients were not required to have albuminuria, except those whose eGFR was greater than or equal to 45 mL/min/1.73 m2.
In DAPA-CKD, the minimum eGFR at entry had to be greater than or equal to 25 mL/min/1.73 m2, and roughly 14% of enrolled patients had an eGFR of less than 30 mL/min/1.73 m2. The average eGFR in DAPA-CKD was about 43 mL/min/1.73 m2. In addition, all patients had at least microalbuminuria, with a minimum urinary albumin-to-creatinine ratio of 200. In CREDENCE, the minimum eGFR for enrollment was 30 mL/min/1.73 m2, and the average eGFR was about 56 mL/min/1.73 m2. All patients in CREDENCE had to have macroalbuminuria, with a urinary albumin-to-creatinine ratio of more than 300.
According to the researchers who designed EMPA-KIDNEY, the trial enrollment criteria aimed to include adults with CKD “who are frequently seen in practice but were under-represented in previous SGLT2 inhibitor trials.”