Trial Search Results

Adaptive COVID-19 Treatment Trial 4 (ACTT-4)

ACTT-4 will evaluate the combination of baricitinib and remdesivir compared to dexamethasone and remdesivir. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests, oropharyngeal (OP) swabs, plasma (Day 29), and serum for secondary research as well as clinical outcome data. However, if infection control or other restrictions limit the ability of the subject to return to the clinic, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone. The primary objective is to evaluate the clinical efficacy of baricitinib + remdesivir versus dexamethasone + remdesivir as assessed by the mechanical ventilation free survival by Day 29.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Institute of Allergy and Infectious Diseases (NIAID)

Stanford Investigator(s):

Intervention(s):

  • Drug: Baricitinib
  • Drug: Dexamethasone
  • Other: Placebo
  • Drug: Remdesivir

Phase:

Phase 3

Eligibility


Inclusion Criteria:

   1. Hospitalized with symptoms suggestive of COVID-19.

   2. 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.

   3. Male or non-pregnant female adult > / = 18 years of age at time of enrollment.

   4. 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.

   5. 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).

   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.

   7. 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:

   1. Prior enrollment in ACTT-3 or ACTT-4. Note: this includes subjects whose participation
   in ACTT was terminated early.

   2. On invasive mechanical ventilation at the time of randomization (ordinal scale
   category 7).

   3. Anticipated discharge from the hospital or transfer to another hospital which is not a
   study site within 72 hours of randomization.

   4. Positive test for influenza virus during the current illness (influenza testing is not
   required by protocol).

   5. Subjects with a low glomerular filtration rate (eGFR), specifically:

      1. 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.

      2. All subjects with an eGFR <15 mL/min

      3. All subjects on hemodialysis and/or hemofiltration at screening, irrespective of
      eGFR are excluded.

   6. Neutropenia (absolute neutrophil count <700 cells/microliter, 0.7 x 10^3/microliter).

   7. Lymphopenia (absolute lymphocyte count <200 cells/microliter, 0.20 x 10^3/microliter).

   8. Received five or more doses of remdesivir including the loading dose, outside of the
   study as treatment for COVID-19.

   9. 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).

10. Allergy to any study medication.

11. Received convalescent plasma or intravenous immunoglobulin [IVIg] for COVID-19, the
   current illness for which they are being enrolled.

12. 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

13. Use of probenecid that cannot be discontinued at study enrollment.

14. 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.

15. 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.

16. 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).

17. 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.

18. 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.

19. Had a known Venous thromboembolism (VTE)(deep vein thrombosis [DVT] or pulmonary
   embolism [PE]) during the current COVID-19 illness.

Ages Eligible for Study

18 Years - 99 Years

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Recruiting