ABSTRACT
BACKGROUND: This study was designed to evaluate if patients with high risk for severe COVID-19 would benefit from treatment with TDF/FTC followed by baricitinib in case of hypoxemia and systemic inflammation. METHODS: PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥ 2 comorbidities or older than 60 years conducted between 10 October 2020 and 23 September 2021. In the first randomization patients received TDF/FTC or not TDF/FTC. In the second randomization patients with room-air O2 saturation <95% and at least one increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in the number of cases and a mortality rate substantially lower than expected EudraCT registration number: 2020-001156-18. RESULTS: Of the 355 included participants 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% CI 0.52-5.91; p= 0.379); it was 0.42 (95% CI 0.11-1.59; p= 0.201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI 0.66-1.40; p = 0.774); it was 0.90 (95%CI 0.61-1.33; p = 0.687) for those treated with baricitinib. CONCLUSIONS: Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials.
ABSTRACT
We evaluated in this randomised, double-blind clinical trial the efficacy of melatonin as a prophylactic treatment for prevention of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Healthcare workers fulfilling inclusion criteria were recruited in five hospitals in Spain and were randomised 1:1 to receive melatonin 2 mg administered orally for 12 weeks or placebo. The main outcome was the number of SARS-CoV-2 infections. A total of 344 volunteers were screened, and 314 were randomised: 151 to placebo and 163 to melatonin; 308 received the study treatment (148 placebo; 160 melatonin). We detected 13 SARS-CoV-2 infections, 2.6% in the placebo arm and 5.5% in the melatonin arm (p = 0.200). A total of 294 adverse events were detected in 127 participants (139 in placebo; 155 in melatonin). We found a statistically significant difference in the incidence of adverse events related to treatment: 43 in the placebo arm and 67 in the melatonin arm (p = 0.040), and in the number of participants suffering from somnolence related to treatment: 8.8% (n = 14) in the melatonin versus 1.4% (n = 2) in the placebo arm (p = 0.008). No severe adverse events related to treatment were reported. We cannot confirm our hypothesis that administration of melatonin prevents the development of SARS-CoV-2 infection in healthcare workers.