Adaptive COVID-19 Treatment Trial 4 (ACTT-4)
COVID-19
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring ACTT, Adaptive, COVID-19, Efficacy, Multicenter, novel coronavirus, Safety
Eligibility Criteria
Inclusion Criteria:
- Hospitalized with symptoms suggestive of COVID-19.
- Subject (or legally authorized representative) 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 enrollment.
- Illness of any duration and has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay (e.g. NAAT, antigen test) in any respiratory specimen or saliva < / = 14 days prior to randomization.
- Within the 7 days prior to randomization requiring new use of supplemental oxygen (or increased oxygen requirement if on chronic oxygen) and requires at the time of randomization low or high flow oxygen devices or use of non-invasive mechanical ventilation (ordinal scale category 5 or 6).
- Women of childbearing potential 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.
Exclusion Criteria:
- Prior enrollment in ACTT-3 or ACTT-4. Note: this includes subjects whose participation in ACTT was terminated early.
- On invasive mechanical ventilation at the time of randomization (ordinal scale category 7).
- Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours of randomization.
- Positive test for influenza virus during the current illness (influenza testing is not required by protocol).
Subjects with a low glomerular filtration rate (eGFR), specifically:
- Subjects with an eGFR 15-30 mL/min are excluded unless in the opinion of the PI, the potential benefit of participation outweighs the potential risk of study participation.
- All subjects with an eGFR <15 mL/min
- All subjects on hemodialysis and/or hemofiltration at screening, irrespective of eGFR are excluded.
- Neutropenia (absolute neutrophil count <700 cells/microliter, 0.7 x 10^3/microliter).
- Lymphopenia (absolute lymphocyte count <200 cells/microliter, 0.20 x 10^3/microliter).
- Received five or more doses of remdesivir including the loading dose, outside of the study as treatment for COVID-19.
- Pregnancy or breast feeding (lactating women who agree to discard breast milk from Day 1 until two weeks after the last study product is given are not excluded).
- Allergy to any study medication.
- Received convalescent plasma or intravenous immunoglobulin [IVIg] for COVID-19, the current illness for which they are being enrolled.
Received any of the following in the two weeks prior to screening as treatment of COVID-19:
- More than one dose of baricitinib for the treatment of COVID-19;
- Other small molecule tyrosine kinase inhibitors (e.g. imatinib, gefitinib, acalabrutinib, etc.);
- monoclonal antibodies targeting cytokines (e.g., TNF inhibitors, anti-interleukin-1 [IL-1], anti-IL-6 [tocilizumab or sarilumab], etc.);
- monoclonal antibodies targeting T-cells or B-cells as treatment for COVID-19. Note: receipt of anti-SARS-CoV-2 monoclonal antibody (mAb) prior to enrollment (e.g. bamlanivimab) for their current COVID-19 illness is not exclusionary
- Use of probenecid that cannot be discontinued at study enrollment.
- Received 6 mg or more of dexamethasone by mouth (po) or Intravenous (IV) (or equivalent for other glucocorticoids) in one day, on more than one day, in the 7 days prior to time of randomization. Note: 6 mg dexamethasone dose equivalents include 40 mg prednisone, 32 mg methylprednisolone and 160 mg hydrocortisone.
- Received > / = 20 mg/day of prednisone po or IV (or equivalent for other glucocorticoids) for > / = 14 consecutive days in the 4 weeks prior to screening.
- Have diagnosis of current active or latent tuberculosis (TB), if known, treated for less than 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.
- Have received any live vaccine (that is, live attenuated) within 4 weeks before screening, or intend to receive a live vaccine (or live attenuated) during the study. Note: Use of non-live (inactivated) vaccinations including SARS-CoV-2 vaccine is allowed for all subjects.
- Had a known Venous thromboembolism (VTE)(deep vein thrombosis [DVT] or pulmonary embolism [PE]) during the current COVID-19 illness.
Sites / Locations
- University of Alabama at Birmingham School of Medicine - Infectious Disease
- UCSF Fresno Center for Medical Education and Research - Clinical Research Center
- University of California San Diego Health - Jacobs Medical Center
- University of California Los Angeles Medical Center - Westwood Clinic
- University of California Irvine Medical Center - Infectious Disease
- VA Palo Alto Health Care System - Infectious Diseases
- University of California Davis Medical Center - Internal Medicine - Infectious Disease
- Kaiser Permanente San Diego Medical Center
- Naval Medical Center San Diego - Infectious Disease Clinic
- University of California San Francisco - Zuckerberg San Francisco General Hospital - Division of Human Immunodeficiency Virus, Infectious Disease, and Global Medicine
- Stanford University - Stanford Hospital and Clinics - Pediatrics - Infectious Diseases
- Cedars Sinai Medical Center
- VA Eastern Colorado Health Care System
- Denver Health Division of Hospital Medicine - Main Campus
- Georgetown University Medical Center - Division of Infectious Diseases
- University of Florida Health - Shands Hospital - Division of Infectious Diseases and Global Medicine
- University of Florida Health - Jacksonville - Department of Emergency Medicine
- University of Miami Miller School of Medicine - Infectious Diseases
- Emory Vaccine Center - The Hope Clinic
- Atlanta VA Medical Center - Infectious Diseases Clinic
- Tripler Army Medical Center
- Northwestern Hospital - Infectious Disease
- University of Illinois at Chicago College of Medicine - Division of Infectious Diseases
- University of Iowa Hospitals & Clinics - Department of Internal Medicine
- Tulane University - Section of Pulmonary Diseases, Critical Care, and Environmental Medicine
- University of Maryland School of Medicine - Center for Vaccine Development - Baltimore
- Johns Hopkins Hospital - Medicine - Infectious Diseases
- Walter Reed National Military Medical Center
- National Institutes of Health - Clinical Center, National Institute of Allergy and Infectious Diseases Laboratory Of Immunoregulation, Clinical Research Section
- Massachusetts General Hospital - Infectious Diseases
- University of Massachusetts Medical School - Infectious Diseases and Immunology
- University of Michigan - Infectious Disease Clinic at Taubman Center
- University of Minnesota Medical Center, Fairview - Infectious Diseases and International Medicine
- Saint Louis University - Center for Vaccine Development
- University of Nebraska Medical Center - Infectious Diseases
- CHI Health Creighton University Medical Center - Bergan Mercy - Pulmonary Medicine
- Atlantic Health System - Morristown Medical Center
- University of New Mexico Clinical and Translational Science Center
- Montefiore Medical Center - Infectious Diseases
- New York University School of Medicine - Langone Medical Center - Microbiology - Parasitology
- University of Rochester Medical Center - Vaccine Research Unit
- Duke Human Vaccine Institute - Duke Vaccine and Trials Unit
- Womack Army Medical Center - Pulmonary and Respiratory Services
- University of Oklahoma Health Science Center - Surgery
- Kaiser Permanente Northwest - Center for Health Research
- Penn State Health Milton S. Hershey Medical Center - Division of Infectious Diseases
- Hospital of the University of Pennsylvania - Infectious Diseases
- University of Pittsburgh - Medicine - Infectious Diseases
- Baylor Scott & White Health - Baylor University Medical Center - North Texas Infectious Disease Consultants
- University of Texas Southwestern Medical Center - Internal Medicine - Infectious Diseases
- Brooke Army Medical Center
- University of Texas Medical Branch - Division of Infectious Disease
- Methodist Hospital - Houston
- Baylor College of Medicine - Molecular Virology and Microbiology
- University of Texas Health Science Center at San Antonio - Infectious Diseases
- University of Utah - Infectious Diseases
- University of Virginia - Acute Care Surgery
- Naval Medical Center Portsmouth - Infectious Disease Division
- EvergreenHealth Infectious Disease Service
- Providence Sacred Heart Medical Center
- Madigan Army Medical Center - Infectious Disease Clinic
- Tokyo Medical and Dental University - Medical Hospital - Department of Respiratory Medicine
- National Center for Global Health and Medicine Hospital - Disease Control and Prevention Center
- Seoul National University Bundang Hospital - Division of Infectious Diseases
- Seoul National University Hospital
- Instituto Nacional de Ciencias Medicas y Nutrición Salvador Zubirán - Departamento de Infectologia
- Instituto Nacional de Enfermedades Respiratorias (INER) - Ismael Cosío Villegas
- National University Health System - Division of Infectious Diseases
- National University Health System - Alexandra Hospital - Division of Infectious Diseases
- National Centre for Infectious Diseases
- Changi General Hospital - Clinical Trials and Research Unit (CTRU)
- Ng Teng Fong General Hospital - Infectious Disease Service
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Remdesivir plus Baricitinib
Remdesivir plus Dexamethasone
200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.