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

Primary Purpose

COVID-19

Status

Active

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Baricitinib (janus kinase inhibitor)

Remdesivir (antiviral) + barictinib (janus kinase inhibitor)

Remdesivir (antiviral)

Tocilizumab (interleukin 6 inhibitor)

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring COVID, coronavirus, SARS-CoV-2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Remdesivir:

Known hypersensitivity to remdesivir or any of its components
Weight below 40 kg
SpO2 ≥ 94% on room air
Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR <30)

Sites / Locations

Nova Scotia Health Authority

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

No Intervention

Arm Label

Baricitinib

Remdesivir

Remdesivir + baricitinib

Tocilizumab

Clinical standard of care

Arm Description

Moderate and severe, not critical disease

Severe, critical disease

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

Outcomes

Primary Outcome Measures

Clinical status of subject at day 15 (on a 7 point ordinal scale).

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.

Length of time to clinical improvement

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

Number of participants that developed Acute Respiratory Distress Syndrome (ARDS) after treatment

Length of time to clinical progression

Time to clinical progression, defined as the time to death, mechanical ventilation, or ICU admission

Cause of death (if applicable)

Sequential Organ Failure Assessment (SOFA) score, daily while hospitalized and on days 15 and 29. (Initial, highest, deltas and mean)

Length of time to normalization of fever

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

Oxygen normalization as defined by: peripheral capillary oxygen saturation (Sp02) > 94% sustained minimum 24 hours.

Duration of supplemental oxygen (if applicable)

Duration of mechanical ventilation (if applicable)

Duration of hospitalization

Adverse events

Full Information

NCT ID

NCT04321993

First Posted

March 24, 2020

Last Updated

September 15, 2023

Sponsor

Lisa Barrett

Collaborators

Nova Scotia Health Authority, Dalhousie University

1. Study Identification

Unique Protocol Identification Number

NCT04321993

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

April 17, 2020 (Actual)

Primary Completion Date

April 2024 (Anticipated)

Study Completion Date

April 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Lisa Barrett

Collaborators

Nova Scotia Health Authority, Dalhousie University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COVID-19

Keywords

COVID, coronavirus, SARS-CoV-2

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

363 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Baricitinib

Arm Type

Experimental

Arm Description

Moderate and severe, not critical disease

Arm Title

Remdesivir

Arm Type

Experimental

Arm Description

Moderate and severe, not critical disease

Arm Title

Remdesivir + baricitinib

Arm Type

Experimental

Arm Description

Moderate and severe, not critical disease

Arm Title

Tocilizumab

Arm Type

Experimental

Arm Description

Severe, critical disease

Arm Title

Clinical standard of care

Arm Type

No Intervention

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Baricitinib (janus kinase inhibitor)

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Remdesivir (antiviral) + barictinib (janus kinase inhibitor)

Intervention Description

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

Intervention Name(s)

Remdesivir (antiviral)

Intervention Description

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

Intervention Name(s)

Tocilizumab (interleukin 6 inhibitor)

Intervention Description

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.

Primary Outcome Measure Information:

Title

Clinical status of subject at day 15 (on a 7 point ordinal scale).

Description

Time Frame

Up to 15 days

Secondary Outcome Measure Information:

Title

Status on an ordinal scale assessed daily while hospitalized and on days 15 and 29 and 180.

Description

Time Frame

Up to 180 days

Title

Length of time to clinical improvement

Description

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.

Time Frame

Up to 29 days

Title

Number of participants with normal pulmonary function and normal O2 saturation on days 11, 15 and 29

Time Frame

Up to 29 days

Title

Number of participants that developed Acute Respiratory Distress Syndrome (ARDS) after treatment

Time Frame

Up to 24 weeks

Title

Length of time to clinical progression

Description

Time to clinical progression, defined as the time to death, mechanical ventilation, or ICU admission

Time Frame

Up to 29 days

Title

Cause of death (if applicable)

Time Frame

Up to 24 weeks

Title

Sequential Organ Failure Assessment (SOFA) score, daily while hospitalized and on days 15 and 29. (Initial, highest, deltas and mean)

Time Frame

Up to 29 days

Title

Length of time to normalization of fever

Description

Fever normalization as defined by: Temperature < 36.6 °C armpit, < 37.2 °C oral, or < 37.8 °C rectal sustained for minimum 24 hours

Time Frame

Up to 29 days

Title

Length of time to normalization of oxygen saturation

Description

Oxygen normalization as defined by: peripheral capillary oxygen saturation (Sp02) > 94% sustained minimum 24 hours.

Time Frame

Up to 29 days

Title

Duration of supplemental oxygen (if applicable)

Time Frame

Up to 29 days

Title

Duration of mechanical ventilation (if applicable)

Time Frame

Up to 29 days

Title

Duration of hospitalization

Time Frame

Up to 29 days

Title

Adverse events

Time Frame

Up to 180 days

Other Pre-specified Outcome Measures:

Title

Global and SARS-CoV-2-specific immune responses before, during and after intervention and in standard of care treatment arm

Time Frame

Up to 180 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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: 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 Remdesivir: Known hypersensitivity to remdesivir or any of its components Weight below 40 kg SpO2 ≥ 94% on room air Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR <30)

Facility Information:

Facility Name

Nova Scotia Health Authority

City

Halifax

State/Province

Nova Scotia

ZIP/Postal Code

B3H 1V7

Country

Canada

12. IPD Sharing Statement

Learn more about this trial

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

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