Treatment of Moderate to Severe Coronavirus Disease (COVID-19) in Hospitalized Patients

NCT ID: NCT04321993

Last Updated: 2023-09-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 363 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-17
• Study Completion Date: 2024-04-30

Brief Summary

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.

Conditions

COVID-19

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Baricitinib

Moderate and severe, not critical disease

Group Type: EXPERIMENTAL

Baricitinib (janus kinase inhibitor)

Intervention Type: DRUG

Baricitinib will be administered as 4 mg po daily for 14 days or until hospital discharge, whichever is sooner.

Remdesivir

Moderate and severe, not critical disease

Group Type: EXPERIMENTAL

Remdesivir (antiviral)

Intervention Type: DRUG

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).

Remdesivir + baricitinib

Moderate and severe, not critical disease

Group Type: EXPERIMENTAL

Remdesivir (antiviral) + barictinib (janus kinase inhibitor)

Intervention Type: DRUG

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.

Tocilizumab

Severe, critical disease

Group Type: EXPERIMENTAL

Tocilizumab (interleukin 6 inhibitor)

Intervention Type: DRUG

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.

Clinical standard of care

Moderate and severe, not critical disease AND severe, critical disease as applicable

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Baricitinib (janus kinase inhibitor)

Baricitinib will be administered as 4 mg po daily for 14 days or until hospital discharge, whichever is sooner.

Intervention Type: 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.

Intervention Type: 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).

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nova Scotia Health Authority

OTHER

Sponsor Role: collaborator

Dalhousie University

OTHER

Sponsor Role: collaborator

Lisa Barrett

OTHER

Sponsor Role: lead

Responsible Party

Lisa Barrett

Clinician Scientist

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Nova Scotia Health Authority

Halifax, Nova Scotia, Canada

Countries

Canada

Other Identifiers

SAIL-004

Identifier Type: -

Identifier Source: org_study_id