ABSTRACT
Background: Recent studies suggest that baricitinib added to dexamethasone may reduce mortality in hospitalized COVID-19 patients requiring supplemental oxygen Methods: In a multicenter open-label, pragmatic, randomized clinical trial in 25 hospitals in Spain we included symptomatic participants with SARS-CoV-2 detected by PCR or antigenic test, with a creatinine clearance >60 mL/min, > 60 years or younger if they had at least two comorbidities (hypertension, obesity, diabetes, cirrhosis, chronic neurologic disease, active cancer, heart failure, coronary heart disease or COPD). Participants were initially randomized to receive or not tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). At any moment during the trial participants with room air 02 saturation < 95% and at least one increased inflammatory biomarker could be randomized to dexamethasone (D) or dexamethasone plus baricitinib (DB). Primary outcome was 28 days mortality. Secondary outcomes were disease progression (increase of O2 requirements, mechanical ventilation or increase in medical therapy: steroid dose, need for starting tocilizumab) Results: Out of the 355 participants included in the trial 287 (80.8%) were randomized to D (n=142) or DB (n=145), 264 (91.9%) simultaneously with the TDF/FTC randomization and 23 (8.1%) later on. Median age 67 years (IQR 62, 73), male (65.5%), with median 8 days of symptoms (IQR 5-10), 28.6% with ≤ 5 days of symptoms, 100% hospitalized, 31.6% with one and 38.7% with ≥ 2 comorbidities (most common: 35.9% hypertension, 9.4% diabetes, 1.7 % obesity), 14.3% receiving remdesivir and 49.1% TDF/FTC. Endpoints in participants treated with D vs. those treated with DB favored DB without achieving statistical significance: mortality 4.9%/2.1%, disease progression 27.5%/24.8%, mechanical ventilation (invasive or noninvasive) 25.4%/23.4%, days since randomization until discharge (median [IQR]) 7 [5, 12]/7 [5, 13.5], discharge before 28 days 89%/94.2%. By Cox regression Hazard Ratio (95% CI) of 28-day mortality was 0.51 (0.13-2.06) for participants treated with DB. Serious adverse events occurred in 9.9%/9.7% of participants treated with D or DB respectively. Adverse events leading to B discontinuation occurred in 3.45% of participants. Conclusion: In this clinical trial of high-risk patients with COVID-19 all disease outcomes favored baricitinb added to dexamethasone but differences did not reach statistical significance. Overall mortality was unexpectedly low.