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Saint Luke’s Mid America Heart Institute and AstraZeneca initiate Phase III DARE-19 trial in COVID-19 patients

April 23, 2020

KANSAS CITY, Mo. - Saint Luke’s Mid America Heart Institute in collaboration with AstraZeneca has initiated a randomized, global Phase III trial to assess the potential of dapagliflozin as a treatment in patients hospitalized with COVID-19 who are at risk of developing serious complications.

The goal of the trial, called DARE-19, is to assess whether dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, can reduce the risk of disease progression, complications, and death due to COVID-19 in patients who also have cardiovascular (CV), metabolic or kidney risk factors.

Cardiovascular, kidney and metabolic comorbidities have been associated with poor outcomes and death in COVID-19 patients. The trial design is supported by extensive data on the protective effect of dapagliflozin in patients with heart failure with reduced ejection fraction (HFrEF), chronic kidney disease (CKD) or type 2 diabetes (T2D).1-5

“Dapagliflozin has demonstrated cardio and renal protective benefits and improved outcomes in high-risk patients with type-2 diabetes, heart failure with reduced ejection fraction, and chronic kidney disease. Patients with COVID-19 and underlying cardiometabolic disease appear to be at the highest risk of morbid complications,” said Mikhail N. Kosiborod, M.D., cardiologist at Saint Luke’s Mid America Heart Institute, Vice President of Research at Saint Luke's Health System, and principal investigator of DARE-19. “Through DARE-19, we hope to decrease the severity of illness, and prevent cardiovascular, respiratory and kidney decompensation, which are common in patients with COVID-19. The study has been organized in record speed, and is an excellent example of how partnerships between academic institutions, industry and research organizations can be mobilized in response to the pandemic, to rapidly and rigorously evaluate potential treatment options”

DARE-19 is an investigator-initiated trial, with the concept developed in collaboration with AstraZeneca, and trial sponsored and executed by the national coordinating center at Saint Luke’s Mid America Heart Institute in collaboration with the academic leaders across several countries, and with operational support from George Clinical, a clinical research organization. The study is being funded by AstraZeneca.

“AstraZeneca is committed to finding new solutions to fight COVID-19 by investigating the application of our new and existing medicines,” said Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D. “With the Phase III DARE-19 trial, we aim to test whether Farxiga can prevent serious complications such as organ failure in those patients with pre-existing health conditions, a critical goal when treating COVID-19.”

The DARE-19 trial is open for enrolment in the US and other countries with a high COVID-19 burden and aims to recruit approximately 900 patients.

DARE-19
DARE-19 is an international, parallel-group, randomized, double-blind, placebo-controlled, investigator-sponsored Phase III trial evaluating the efficacy and safety of dapagliflozin in addition to background local standard of care therapy, on the risk of all-cause death or disease progression and complications in adults who are hospitalized with COVID-19 at the time of trial enrolment. Patients enrolled in DARE-19 also have a medical history of hypertension (HTN), atherosclerotic CV disease, Heart failure with reduced or preserved ejection fraction, T2D or CKD Stage III to IV. The primary efficacy outcome of the trial is time to first occurrence of death from any cause or new/worsened organ dysfunction through 30 days of follow-up.

Some of the patients at highest risk of COVID-19 complications appear to be those with cardiometabolic disease. 6,7,8 CV complications, including acute myocardial injury and heart failure (HF) are common in COVID-19, and appear to be key drivers of poor outcomes and death especially in patients with pre-existing CV disease and/or CKD. 9,10

Saint Luke’s Mid America Heart Institute
Saint Luke’s Mid America Heart Institute is a member of Saint Luke’s Health System, which consists of 18 area hospitals and several primary and specialty care practices, and provides a range of inpatient, outpatient, and home care services. Founded as a faith-based, not-for-profit organization, our mission includes a commitment to the highest levels of excellence in health care and the advancement of medical research and education. The health system is an aligned organization in which the physicians and hospitals assume responsibility for enhancing the physical, mental, and spiritual health of people in the metropolitan Kansas City area and the surrounding region.

References

1. Wiviott SD, Raz I, Bonaca MP, et al, for the DECLARE-TIMI 58 Investigators. Dapagliflozin and cardiovascular outcomes in type 2 diabetes [article and supplementary appendix]. N Engl J Med. 2019:380:347-357.
2. McMurray JJV, Solomon SD, Inzucchi SE, et al, on behalf of the DAPA-HF Committees and Investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction [article, online protocol, and supplementary appendix]. N Engl J Med. 2019;318;1995-2008.
3. Solomon SD, Jhund P, Kosiborod MN, et al. Effect of dapagliflozin on renal function in heart failure with reduced ejection fraction: the DAPA-HF Trial [presentation]. Presented at American Society of Nephrology Kidney Week; November 5-10, 2019; Washington, DC.
4. AstraZeneca Pharmaceuticals LP. Farxiga Phase III DAPA-CKD trial will be stopped early after overwhelming efficacy in patients with chronic kidney disease [press release]. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/…. Published March 30, 2020. Accessed April 7, 2020.
5. Sabatine MS, DeMets DL, Inzucchi SE, et al. Timing of onset of clinical benefit with dapagliflozin in patients with heart failure: an analysis from DAPA-HF [presentation]. Presented at: American Heart Association Scientific Sessions; November 16-18, 2019; Philadelphia, PA.
6. Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State [published online ahead of print March 19, 2020]. JAMA. 2020.
7. Center for Disease Control. Coronavirus Disease 2019 (COVID-19): interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19). Website. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-managem…. Accessed April 2, 2020.
8. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese center for disease control and prevention [published online ahead of print February 24, 2020]. JAMA. 2020.
9. Madjid M, Safavi-Naeini P, Solomon SD, et al. Potential effects of coronaviruses on the cardiovascular system: a review [published online ahead of print March 27, 2020]. JAMA Cardiol. 2020. http://dx.doi.org/10.1001/jamacardio.2020.1286. Accessed April 2, 2020.
10. Cheng Y, Luo R, Wang K, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020. http://dx.doi.org/10.1016/j.kint.2020.03.005. Accessed April 3, 2020.