ABSTRACT
BACKGROUND: Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. METHODS: Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. RESULTS: Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49-69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI - 0.1% [- 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (- 3.2% [- 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. CONCLUSION: This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu ( 2022-500385-99-00 ).
Subject(s)
COVID-19 , Humans , Adult , Male , Middle Aged , Female , SARS-CoV-2 , RNA, Viral , COVID-19 Drug Treatment , Double-Blind MethodABSTRACT
OBJECTIVE: Coronavirus disease 2019 (COVID-19) has a high incidence of intensive care admittance due to the severe acute respiratory syndrome (SARS). Intensive care unit (ICU)-acquired weakness (ICUAW) is a common complication of ICU patients consisting of symmetric and generalised weakness. The aim of this study was to determine the presence of myopathy, neuropathy or both in ICU patients affected by COVID-19 and whether ICUAW associated with COVID-19 differs from other aetiologies. METHODS: Twelve SARS CoV-2 positive patients referred with the suspicion of critical illness myopathy (CIM) or polyneuropathy (CIP) were included between March and May 2020. Nerve conduction and concentric needle electromyography were performed in all patients while admitted to the hospital. Muscle biopsies were obtained in three patients. RESULTS: Four patients presented signs of a sensory-motor axonal polyneuropathy and seven patients showed signs of myopathy. One muscle biopsy showed scattered necrotic and regenerative fibres without inflammatory signs. The other two biopsies showed non-specific myopathic findings. CONCLUSIONS: We have not found any distinctive features in the studies of the ICU patients affected by SARS-CoV-2 infection. SIGNIFICANCE: Further studies are needed to determine whether COVID-19-related CIM/CIP has different features from other aetiologies. Neurophysiological studies are essential in the diagnosis of these patients.