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

COVID-19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04321993
• Other study ID #: SAIL-004
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 17, 2020
• Est. completion date: April 2024

Study information

• Verified date: September 2023
• Source: Nova Scotia Health Authority
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 363
• Est. completion date: April 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Coronavirus Infections
• COVID-19

Intervention

Drug:
• Baricitinib (janus kinase inhibitor)
Baricitinib will be administered as 4 mg po daily for 14 days or until hospital discharge, whichever is sooner.
• 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.
• 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).
• 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.

Locations

Country	Name	City	State
Canada	Nova Scotia Health Authority	Halifax	Nova Scotia

Sponsors (3)

Lead Sponsor	Collaborator
Lisa Barrett	Dalhousie University, Nova Scotia Health Authority

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Global and SARS-CoV-2-specific immune responses before, during and after intervention and in standard of care treatment arm		Up to 180 days
Primary	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.	Up to 15 days
Secondary	Status on an ordinal scale assessed daily while hospitalized and on days 15 and 29 and 180.	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.	Up to 180 days
Secondary	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.	Up to 29 days
Secondary	Number of participants with normal pulmonary function and normal O2 saturation on days 11, 15 and 29		Up to 29 days
Secondary	Number of participants that developed Acute Respiratory Distress Syndrome (ARDS) after treatment		Up to 24 weeks
Secondary	Length of time to clinical progression	Time to clinical progression, defined as the time to death, mechanical ventilation, or ICU admission	Up to 29 days
Secondary	Cause of death (if applicable)		Up to 24 weeks
Secondary	Sequential Organ Failure Assessment (SOFA) score, daily while hospitalized and on days 15 and 29. (Initial, highest, deltas and mean)		Up to 29 days
Secondary	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	Up to 29 days
Secondary	Length of time to normalization of oxygen saturation	Oxygen normalization as defined by: peripheral capillary oxygen saturation (Sp02) > 94% sustained minimum 24 hours.	Up to 29 days
Secondary	Duration of supplemental oxygen (if applicable)		Up to 29 days
Secondary	Duration of mechanical ventilation (if applicable)		Up to 29 days
Secondary	Duration of hospitalization		Up to 29 days
Secondary	Adverse events		Up to 180 days