Clinical trial NCT04321993: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: COVID-19
Keywords: COVID
coronavirus
SARS-CoV-2
Lead sponsor: Nova Scotia Health Authority
Sponsor class: OTHER
Collaborators: name: Nova Scotia Health Authority
name: Dalhousie University
First posted: 2020-03-26
Enrollment: 363
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Clinical status of subject at day 15 (on a 7 point ordinal scale).
timeFrame: Up to 15 days
Secondary outcomes:
measure: Status on an ordinal scale assessed daily while hospitalized and on days 15 and 29 and 180.
timeFrame: Up to 180 days
measure: Length of time to clinical improvement
timeFrame: Up to 29 days
measure: Number of participants with normal pulmonary function and normal O2 saturation on days 11, 15 and 29
timeFrame: Up to 29 days
measure: Number of participants that developed Acute Respiratory Distress Syndrome (ARDS) after treatment
timeFrame: Up to 24 weeks
measure: Length of time to clinical progression
timeFrame: Up to 29 days
measure: Cause of death (if applicable)
timeFrame: Up to 24 weeks
measure: Sequential Organ Failure Assessment (SOFA) score, daily while hospitalized and on days 15 and 29. (Initial, highest, deltas and mean)
timeFrame: Up to 29 days
measure: Length of time to normalization of fever
timeFrame: Up to 29 days
measure: Length of time to normalization of oxygen saturation
timeFrame: Up to 29 days
measure: Duration of supplemental oxygen (if applicable)
timeFrame: Up to 29 days
measure: Duration of mechanical ventilation (if applicable)
timeFrame: Up to 29 days
measure: Duration of hospitalization
timeFrame: Up to 29 days
measure: Adverse events
timeFrame: Up to 180 days
Other outcomes:
measure: Global and SARS-CoV-2-specific immune responses before, during and after intervention and in standard of care treatment arm
timeFrame: Up to 180 days
Locations:
city: Halifax
country: Canada
facility: Nova Scotia Health Authority
state: Nova Scotia
Study officials:
References: