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

Sponsor

Lisa Barrett (Other)

Overall Status

Recruiting

CT.gov ID

NCT04321993

Collaborator

Nova Scotia Health Authority (Other), Dalhousie University (Other)

800

Enrollment

Location

Arms

34.4

Anticipated Duration (Months)

23.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: Baricitinib (janus kinase inhibitor) Drug: Remdesivir (antiviral) + barictinib (janus kinase inhibitor) Drug: Remdesivir (antiviral) Drug: Tocilizumab (interleukin 6 inhibitor)	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

800 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 17, 2020

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Baricitinib Moderate and severe, not critical disease	Drug: Baricitinib (janus kinase inhibitor) Baricitinib will be administered as 4 mg po daily for 14 days or until hospital discharge, whichever is sooner.
Experimental: Remdesivir Moderate and severe, not critical disease	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).
Experimental: Remdesivir + baricitinib Moderate and severe, not critical disease	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.
Experimental: Tocilizumab Severe, critical disease	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.
No Intervention: Clinical standard of care Moderate and severe, not critical disease AND severe, critical disease as applicable

Outcome Measures

Primary Outcome Measures

Clinical status of subject at day 15 (on a 7 point ordinal scale). [Up to 15 days]
Not hospitalized, no limitations on activities Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death.

Secondary Outcome Measures

Status on an ordinal scale assessed daily while hospitalized and on days 15 and 29 and 180. [Up to 180 days]
Not hospitalized, no limitations on activities Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death.
Length of time to clinical improvement [Up to 29 days]
Time to clinical improvement is defined as the time to normalization of respiratory rate, fever, and oxygen saturation, and alleviation of cough within 72 hours.
Number of participants with normal pulmonary function and normal O2 saturation on days 11, 15 and 29 [Up to 29 days]
Number of participants that developed Acute Respiratory Distress Syndrome (ARDS) after treatment [Up to 24 weeks]
Length of time to clinical progression [Up to 29 days]
Time to clinical progression, defined as the time to death, mechanical ventilation, or ICU admission
Cause of death (if applicable) [Up to 24 weeks]
Sequential Organ Failure Assessment (SOFA) score, daily while hospitalized and on days 15 and 29. (Initial, highest, deltas and mean) [Up to 29 days]
Length of time to normalization of fever [Up to 29 days]
Fever normalization as defined by: Temperature < 36.6 °C armpit, < 37.2 °C oral, or < 37.8 °C rectal sustained for minimum 24 hours
Length of time to normalization of oxygen saturation [Up to 29 days]
Oxygen normalization as defined by: peripheral capillary oxygen saturation (Sp02) > 94% sustained minimum 24 hours.
Duration of supplemental oxygen (if applicable) [Up to 29 days]
Duration of mechanical ventilation (if applicable) [Up to 29 days]
Duration of hospitalization [Up to 29 days]
Adverse events [Up to 180 days]

Other Outcome Measures

Global and SARS-CoV-2-specific immune responses before, during and after intervention and in standard of care treatment arm [Up to 180 days]
Percent of subjects with SARS-CoV-2 detectable in blood at days 3, 5, 8, 11, 15, 29 and 180. [Up to 180 days]
Quantitative SARS-CoV-2 viral load in blood at days 3, 5, 8, and 11, 15, 29, and 180. [Up to 180 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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:

Concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 is prohibited < 24 hours prior to study medication initiation
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:

Contraindicated for patients with known hypersensitivity to baricitinib or to any of the excipients.
Prior untreated latent tuberculosis
Any individuals with TB risk factors will not be enrolled in the baricitinib arm of the study.
Presence of active viral hepatitis C or B
People with a clinical history of invasive or active fungal infection
People with a clinical history of active CMV disease in the last year
Patients who are pregnant or breastfeeding
Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR <15)

Tocilizumab:

Known hypersensitivity to tocilizumab or any of its components
Prior untreated latent tuberculosis
Any individuals with TB risk factors will not be enrolled in the tocilizumab arm of the study.
Presence of active viral hepatitis C or B
People with a clinical history of invasive or active fungal infection
People with a clinical history of active CMV disease in the last year
CRP<75 mg/L
SpO2 ≥ 92% on room air