Clinical trial investigates dapagliflozin for COVID-19 treatment

Recruitment for a global phase 3 trial is now underway to assess the potential of the SGLT2 inhibitor dapagliflozin as a treatment to reduce COVID-19 progression, complications and death among adults with cardiovascular, metabolic or renal risk factors, according to a press release from AstraZeneca and St. Luke’s Mid America Heart Institute.

The goal of the trial, called DARE-19, is to assess whether dapagliflozin (Farxiga) could become a treatment option for adults with COVID-19 who are at risk for developing serious complications, such as organ failure. The trial design is supported by extensive data on the protective effect of dapagliflozin among adults with heart failure with reduced ejection fraction (HFrEF), chronic kidney disease or type 2 diabetes.

“Patients with cardiometabolic conditions — atherosclerotic CVD, heart failure, hypertension, type 2 diabetes or CKD — are at substantially higher risk for morbid complications and death in the setting of COVID—19,” Mikhail Kosiborod, MD, FACC, FAHA, cardiologist at Saint Luke’s Mid America Heart Institute, professor of medicine at the University of Missouri-Kansas City School of Medicine and a principal investigator for DARE-19, told Healio. “Furthermore, the emerging data indicate that in addition to respiratory decompensation, cardiovascular and kidney related complications are common, and appear to be key drivers of poor outcomes. It thus follows that prevention of these complications in high-risk patients may lead to reduction in the disease severity and lower risk for morbid events and death. SGLT2 inhibitors have previously shown substantial cardio- and nephroprotective effects among patients with cardiometabolic conditions, and may provide target organ protection in the setting of COVID-19.”

DARE-19 is an international, parallel-group, randomized, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy and safety of dapagliflozin in addition to background, local standard of care therapy on the risk for all-cause death or disease progression and complications in adults hospitalized with COVID-19 at the time of trial enrolment. Patients enrolled in DARE-19 also have a medical history of hypertension, atherosclerotic CVD, HFrEF, HFpEF, type 2 diabetes or stage 3 or 4 CKD. The primary efficacy outcome is time to first occurrence of death from any cause or new or worsening organ dysfunction through 30 days of follow-up. The DARE-19 trial is open for enrollment in the U.S. and European countries with a high COVID-19 burden and aims to recruit approximately 900 patients, according to the release.

“SGLT2 inhibitors may favorably influence the underlying mechanistic processes dysregulated in the setting of acute illness, including effects on energy metabolism, autophagy, oxidative stress, and inflammation,” Kosiborod said in an interview. “There is currently no information on the use of dapagliflozin in patients being treated for COVID-19. The DARE-19 trial will assess both the efficacy and the safety of dapagliflozin in this patient population in the closely monitored environment of a rigorously designed clinical trial.”

Kosiborod said the trial protocol excludes people with type 1 diabetes, or those at high risk for diabetic ketoacidosis. Concern has been raised during previous trials about the risk for DKA with use of SGLT inhibitors for treatment of type 1 diabetes.

“This trial includes detailed, specific instructions to ensure careful monitoring for DKA, including frequent assessments of acid base status in the hospital setting,” Kosiborod said. “The safety data will be closely monitored by an independent data monitoring committee. “

“AstraZeneca is committed to finding new solutions to fight COVID-19 by investigating the application of our new and existing medicines,” Mene Pangalos, executive vice president of biopharmaceuticals research and development at AstraZeneca, said in the release. “With the phase 3 DARE-19 trial, we aim to test whether Farxiga can prevent serious complications such as organ failure.”

Some of the patients at highest risk for COVID-19 complications appear to be those with cardiometabolic disease; however, there is debate regarding the best course of treatment. As Healio previously reported, researchers are examining the use of other diabetes medications, such as DPP-IV inhibitors or GLP-1 receptor agonists, as potential treatments for adults with COVID-19.

Kosiborod said researchers plan to enroll patients in DARE-19 during the next several months and hope to have the initial data before the end of this year. – by Regina Schaffer

Disclosures: Kosiborod reports he received grant/research support from AstraZeneca and Boehringer Ingelheim, honoraria from AstraZeneca, Boehringer Ingelheim and Novo Nordisk, and consultant fees from Amarin, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, GlaxoSmithKline, Glytec, Intarcia, Janssen, Merck, Novartis, Novo Nordisk and Sanofi Aventis.