Methods |
Drug name: infliximab, abatacept, remdesivir, cenicriviroc Trial design: randomised, parallel assignment, masking: triple (participant, investigator, outcome assessor) NCT number: NCT04593940 Target sample size: 2160 participants Planned completion date: September 2021 |
Participants |
Setting
Inpatient
Multicentre, USA
Eligibility criteria
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Inclusion criteria
Admitted to a hospital or awaiting admission in the ED with symptoms suggestive of COVID‐19
Participant (or LAR) provides informed consent prior to initiation of any study procedures
Participant (or LAR) understands and agrees to comply with planned study procedures
Male or non‐pregnant female adults ≥ 18 years of age at time of enrolment
Has laboratory‐confirmed (within 14 days prior to enrolment) SARS‐CoV‐2 infection as determined by PCR or other commercial or public health assay in any specimen
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Ongoing illness of any duration, and at least one of the following:
radiographic infiltrates by imaging (chest X‐ray, CT scan, etc.)
SpO2 ≤ 94% on room air
requiring supplemental oxygen
requiring mechanical ventilation or ECMO
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 60
Agrees to not participate in another intervention trial for the treatment of COVID‐19 through day 60
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Exclusion criteria:
ALT or AST > 5 times the ULN
Estimated glomerular filtration rate (eGFR) < 30 mL/min (including patients receiving haemodialysis or hemofiltration)
Neutropenia (absolute neutrophil count < 1000 cells/μL) (< 1.0 x 103/μL or < 1.0 GI/L)
Lymphopenia (absolute lymphocyte count < 200 cells/μL) (< 0.20 x 103/μL or < 0.20 GI/L)
Pregnancy or breastfeeding
Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours
Known allergy to any study medication
Received cytotoxic or biologic treatments (such as anti‐interleukin‐1, anti‐IL‐6 (tocilizumab or sarilumab), IL‐17, or T‐cell‐ or B‐cell‐targeted therapies (e.g. rituximab), tyrosine kinase inhibitors including baricitinib, TNF inhibitors, or interferon within 4 weeks or 5 half‐lives prior to screening
Suspected clinical diagnosis of current active tuberculosis (TB) or latent TB treated for < 4 weeks
Based on medical history and concomitant therapies that would suggest infection, suspected serious, active bacterial, fungal, viral (including, but not limited to, active HBV, HCV, or HIV/AIDS)
Live vaccine (that is, live attenuated) within 3 months before screening
Severe hepatic impairment (defined as liver cirrhosis Child stage C)
Current severe heart failure (NYHA III‐IV)
In the investigator's judgment, the patient has any advanced organ dysfunction that would not make participation appropriate
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Interventions |
Intervention
Infliximab (single dose, IV infusion, 5 mg/kg)
Abatacept (single dose, IV infusion, 10 mg/kg)
Remdesivir (removed)
Cenicriviroc (loading dose: 450 mg (300 mg morning and 150 mg evening, day 2‐29: 300 mg)
Comparator
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Outcomes |
Efficacy outcomes
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All‐cause mortality
Clinical progression/improvement of symptoms: planned
Length of hospital stay: planned as time to recovery
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
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Notes |
Funding: National Center for Advancing Translational Science (NCATS) and Biomedical Advanced Research and Development Authority |