Investigational medications adjunct to clinical standard of care treatment will be assessed to evaluate safety and effectiveness as an anti-COVID-19 treatment. All hospitalized persons with moderate to severe COVID-19 disease that meet eligibility criteria will be offered participation.
Drug: Baricitinib (janus kinase inhibitor)
Baricitinib will be administered as 4 mg po daily for 14 days or until hospital discharge, whichever is sooner.
Drug: Remdesivir (antiviral) + barictinib (janus kinase inhibitor)
Remdesivir will be administered as a loading dose of 200 mg IV over one hour on day 1 followed by 100 mg IV daily over one hour on days 2-5 (with a possibility to extend to up to 10 days total).
Baricitinib will be administered as 4 mg po daily for 14 days or until hospital discharge, whichever is sooner.
Drug: Remdesivir (antiviral)
Remdesivir will be administered as a loading dose of 200 mg IV over one hour on day 1 followed by 100 mg IV daily over one hour on days 2-5 (with a possibility to extend to up to 10 days total).
Drug: Tocilizumab (interleukin 6 inhibitor)
Tocilizumab will be administered as a single IV infusion over one hour. Dosage will be 8 mg/kg total bodyweight up to a maximum of 800 mg.
Inclusion Criteria:
- 18 years or older
- Moderate to severe COVID-19 associated disease as defined by the WHO
- Willing and able to provide informed consent prior to performing study procedures
- Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other
commercial or public health assay
- Illness of any duration, and at least one of the following: Radiographic infiltrates
by imaging (chest x-ray, CT scan, etc.), or Clinical assessment (evidence of
rales/crackles on exam) AND SpO2 ≤ 94% on room air, or Require mechanical ventilation
and/or supplemental oxygen.
- Normal potassium, magnesium, and calcium levels pre-therapy when used in agents at
risk of QT prolongation
Patients will be further distinguished based on their disease severity into one of two
categories:
- Moderate and severe, not critical disease: patients with SpO2 ≤ 94% on room air, and
those who require supplemental oxygen
- Severe, critical disease: patients with critical illness requiring ICU-level care
including requiring mechanical ventilation or ECMO, and/or end organ dysfunction as
seen in sepsis/septic shock.
Exclusion Criteria:
- Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 X upper limit
of normal (ULN)
- Consideration by the investigator, for any reason, that the subject is an unsuitable
candidate to receive study treatment Medication specific Exclusion
Baricitinib:
1. Contraindicated for patients with known hypersensitivity to baricitinib or to any of
the excipients.
2. Prior untreated latent tuberculosis
3. Any individuals with TB risk factors will not be enrolled in the baricitinib arm of
the study.
4. Presence of active viral hepatitis C or B
5. People with a clinical history of invasive or active fungal infection
6. People with a clinical history of active CMV disease in the last year
7. Patients who are pregnant or breastfeeding
8. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR <15)
Tocilizumab:
1. Known hypersensitivity to tocilizumab or any of its components
2. Prior untreated latent tuberculosis
3. Any individuals with TB risk factors will not be enrolled in the tocilizumab arm of
the study.
4. Presence of active viral hepatitis C or B
5. People with a clinical history of invasive or active fungal infection
6. People with a clinical history of active CMV disease in the last year
7. CRP<75 mg/L
8. SpO2 ≥ 92% on room air
Remdesivir:
1. Known hypersensitivity to remdesivir or any of its components
2. Weight below 40 kg
3. SpO2 ≥ 94% on room air
4. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR <30)
Nova Scotia Health Authority
Halifax, Nova Scotia, Canada