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

Lisa Barrett

Status and phase: Active, not recruiting; Phase 2

Conditions: COVID-19

Treatments: Drug: Remdesivir (antiviral) + barictinib (janus kinase inhibitor); Drug: Remdesivir (antiviral); Drug: Tocilizumab (interleukin 6 inhibitor); Drug: Baricitinib (janus kinase inhibitor)

Study type: Interventional

Funder types: Other

Identifiers

NCT04321993

SAIL-004

Details and patient eligibility

About

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.

Enrollment: 363 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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363 participants in 5 patient groups

Baricitinib

Experimental group

Description:

Moderate and severe, not critical disease

Treatment:

Drug: Baricitinib (janus kinase inhibitor)

Remdesivir

Experimental group

Description:

Moderate and severe, not critical disease

Treatment:

Drug: Remdesivir (antiviral)

Remdesivir + baricitinib

Experimental group

Description:

Moderate and severe, not critical disease

Treatment:

Drug: Remdesivir (antiviral) + barictinib (janus kinase inhibitor)

Tocilizumab

Experimental group

Description:

Severe, critical disease

Treatment:

Drug: Tocilizumab (interleukin 6 inhibitor)

Clinical standard of care

No Intervention group

Description:

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