Covid-19 Living Data

Trial NCT04891133; EudraCT 2021-000541-41; EU CTIS 2022-500385-99-00
Publication Bari-SolidAct - Troseid M, SSRN (2022) (preprint)
Dates: 2021-06-03 to 2022-03-07
Funding: Mixed (European Commission; EU-SolidAct is part of the European pandemic preparedness network EU RESPONSE, funded by the EU Horizon 2020 Research and Innovation Programme. EU-SolidAct has also received funding from CAPNET (France) and Klinbeforsk (Norway). The baricitinib drug and matching placebo were provided by Eli Lilly and Company. )
Conflict of interest: Yes

Methods
	RCT Blinding: triple blinding
	Location : Multicenter / Austria, Belgium, France, Ireland, Italy, Luxembourg, Norway, Portugal, Spain Follow-up duration (days): 90
Inclusion criteria	Adults (≥18 years) SARS CoV-2 infection confirmed by a polymerase chain reaction (PCR) no more than 9 days old admitted to hospital with severe or critical COVID-19, defined as one of the following: i) SpO2 <90% on room air, ii) SpO2 90-94% with a downwards trend and/or signs of respiratory distress, iii) need of oxygen by non-invasive ventilation (NIV)/continuous positive airway pressure (CPAP), high flow oxygen or non-rebreather mask, or iv) need of mechanical ventilation or ECMO
Exclusion criteria	Suspected serious infection besides COVID-19 recent or recurrent thromboembolism neutropenia severe lymphopenia severe renal dysfunction pregnancy breast feeding known hypersensitivity to constituents of study drugs participation in a potentially confounding trial immunosuppressive drugs including JAK inhibitors, except short term treatment (up to 4 days) with corticosteroids for COVID-19. During the trial, amendments of eligibility criteria included stricter cut- off for excluding patients with renal dysfunction (from eGFR below 15 to below 30) for consistency with other baricitinib protocols. In addition, the protocol was amended for inclusion of immunocompromised patients with elevation of 2 or more inflammatory markers above the following cut-offs: ferritin > 700 ug/l, lactate dehydrogenase > 400 U/L, C-reactive protein (CRP) >75 mg/L
Interventions
	Treatment Baricitinib 4 mg orally once a day for up to 14 days
	Control Placebo
Participants
	Randomized participants : Placebo=142 Baricitinib=142
	Characteristics of participants N= 284 Mean age : NR 211 males Severity : Mild: n=0 / Moderate: n=0 / Severe: n=236 Critical: n=39 Number of vaccinated participants: NR
Primary outcome
	In the register Occurrence of death within 60 days (primary end point, EU SolidAct part B) [ Time Frame: 60 days ]
	In the report Occurrence of death within 60 days (measured on day 61 after inclusion).
Documents available	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the preprint article, the prospective trial registry was used in data extraction and assessment of risk of bias. Neither protocol nor statistical analysis plan were available. The supplementary appendices referred to in the article were not accessible with the preprint version. There is no change from the trial registration in the intervention and control treatments. The primary and secondary outcomes in the article reflect those in the registry. The trial (n = 275) did not achieve its target sample size (n = 1900) because the trial was stopped before reaching the planned sample size due to external evidence from the Recovery trial indicating survival benefit of baricitinib in the trial population.