Protocol for a 30-day randomised, parallel-group, non-inferiority, controlled trial investigating the effects of discontinuing renin-angiotensin system inhibitors in patients with and without COVID-19: the RASCOVID-19 trial.

INTRODUCTION: The COVID-19 pandemic caused by the virus SARS-CoV has spread rapidly and caused damage worldwide. Data suggest a major overrepresentation of hypertension and diabetes among patients experiencing severe courses of COVID-19 including COVID-19-related deaths. Many of these patients receive renin-angiotensin system (RAS) inhibiting therapy, and evidence suggests that treatment with angiotensin II receptor blockers (ARBs) could attenuate SARS-CoV-induced acute respiratory distress syndrome, and ACE inhibitors and ARBs have been suggested to alleviate COVID-19 pulmonary manifestations. This randomised clinical trial will address whether RAS inhibiting therapy should be continued or discontinued in hospitalised patients with COVID-19. METHODS AND ANALYSIS: This trial is a 30-day randomised parallel-group non-inferiority clinical trial with an embedded mechanistic substudy. In the main trial, 215 patients treated with a RAS inhibitor will be included. The participants will be randomly assigned in a 1:1 ratio to either discontinue or continue their RAS inhibiting therapy in addition to standard care. The patients are included during hospitalisation and followed for a period of 30 days. The primary end point is number of days alive and out of hospital within 14 days after recruitment. In a mechanistic substudy, 40 patients treated with RAS inhibition, who are not in hospital and not infected with COVID-19 will be randomly assigned to discontinue or continue their RAS inhibiting therapy with the primary end point of serum ACE2 activity. ETHICS AND DISSEMINATION: This trial has been approved by the Scientific-Ethical Committee of the Capital Region of Denmark (identification no. H-20026484), the Danish Medicines Agency (identification no. 2020040883) and by the Danish Data Protection Agency (P-2020-366). The results of this project will be compiled into one or more manuscripts for publication in international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: 2020-001544-26; NCT04351581.

The Impact of Diabetes on Mortality and Clinical Outcomes in Hospitalized Patients with COVID-in the Capital Region of Denmark

During the COVID-pandemic, patients diagnosed with diabetes have been overrepresented among patients admitted to hospital with COVID-19. We explored the impact of diabetes on mortality and clinical outcomes in hospitalized patients with COVID-in the Capital Region of Denmark. All patients from the Capital Region of Denmark admitted to hospital with COVID-in the period from February 2020 to March 2021 were included. Patients with a diabetes diagnosis were compared to patients without a diabetes diagnosis in multivariable adjusted analyses. The primary outcome was death within 30 days from hospitalization. Secondary outcomes included time to discharge, use of oxygen treatment, referral to intensive care unit, and use of respirator. Among 3,997 hospital admitted patients, 1,186 had diabetes (1,090 type 2 diabetes;96 type 1 diabetes) . The patients with diabetes were 59% men, 72±13 years (mean±standard deviation) with BMI 28±6.4 kg/m2, while patients without diabetes were 51% men, 67±years with BMI 26±5.8 kg/m2. Within 30 days, 292 (24.6%) patients with diabetes died compared to 521 (18.5%) without diabetes (adjusted odds ratio (aOR) 1.28 (95% CI 1.02-1.6) for death) . Patients with diabetes were 24% less likely to be discharged alive at any given time compared to patients without diabetes with a hazard ratio of 0.76 (0.70-0.81) . aOR for oxygen treatment was 1. (0.97-1.47) , for referral to intensive care unit 1.37 (1.01-1.85) , and for use of respirator 1. (0.86-1.65) . We found that hospitalized COVID-patients with diabetes had a 28% higher risk of dying within 30 days and were 19% more likely to receive intensive care treatment than hospitalized COVID-patients without diabetes.