Methods |
Drug name: baricitinib, dexamethasone, remdesivir Trial design: multicenter, adaptive, randomised blinded controlled trial Identifiers: NCT04640168 Target sample size: 1500 participants Planned completion date: June 2021 |
Participants |
Setting
Inpatient
Multicentre: USA, Japan, Republic of Korea, Mexico, Singapore
Eligibility criteria
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Inclusion criteria
Hospitalised with symptoms suggestive of COVID‐19
Participant (or LAR) provides informed consent prior to initiation of any study procedures and understands and agrees to comply with planned study procedures
Male or non‐pregnant female adult ≥ 18 years of age at time of enrolment
Illness of any duration and has laboratory‐confirmed SARS‐CoV‐2 infection as determined by PCR or other commercial or public health assay (e.g. NAAT, antigen test) in any respiratory specimen or saliva ≤ 14 days prior to randomisation
Within the 7 days prior to randomisation requiring new use of supplemental oxygen (or increased oxygen requirement if on chronic oxygen) and requires at the time of randomisation low‐ or high‐flow oxygen devices or use of non‐invasive mechanical ventilation (ordinal scale category 5 or 6)
WOCBP must agree to either abstinence or use at least one primary form of contraception not including hormonal contraception from the time of screening through day 29
Agrees not to participate in another blinded clinical trial (both pharmacologic and other types of interventions) for the treatment of COVID‐19 through day 29
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Exclusion criteria
Prior enrolment in ACTT‐3 or ACTT‐4
On invasive mechanical ventilation at the time of randomisation (ordinal scale category 7)
Anticipated discharge from the hospital or transfer to another hospital that is not a study site within 72 h of randomisation
Positive test for influenza virus during the current illness
Received ≥ 5 doses of remdesivir including the loading dose, outside of the study as treatment for COVID‐19
Pregnancy or breastfeeding
Allergy to any study medication
Received convalescent plasma or IVIg for COVID‐19, small molecule tyrosine kinase inhibitors, mAbs targeting cytokines, mAbs targeting T‐cells or B‐cells as treatment for COVID‐19
Use of probenecid that cannot be discontinued at study enrolment
Received > 1 dose of dexamethasone ≥ 6 mg (or equivalent for other glucocorticoids) in the 7 days prior to time of randomisation
Received ≥ 20 mg/day of prednisone (or equivalent for other glucocorticoids) for ≥ 14 consecutive days in the 4 weeks prior to screening
Have diagnosis of current active or latent tuberculosis, if known, treated for < 4 weeks with appropriate therapy (by history only, no screening required)
Serious infection (besides COVID‐19), immunosuppressive state, or immunosuppressive medications that in the opinion of the investigator could constitute a risk when taking baricitinib or dexamethasone
Live vaccine (that is, live attenuated) within 4 weeks before screening, or intend to receive a live vaccine (or live attenuated) during the study
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Interventions |
Intervention
Remdesivir
Baricitinib
Dexamethasone
Comparator
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Outcomes |
Efficacy outcomes
-
All‐cause mortality
Clinical progression/improvement of symptoms: planned
Length of hospital stay: planned
Admission to ICU: not planned
Length of ICU stay: not planned
Quality of life, including fatigue: not planned
Viral clearance: not planned
Safety outcomes
Additional study outcomes
Change from baseline in ALT, AST, C‐reactive protein, creatinine, d‐dimer concentration, glucose, haemoglobin, platelets, prothrombin time, total bilirubin, WBC count
Desirability of Outcome Ranking (DOOR)
Time to recovery
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Notes |
Funding: NIAID |