Treatment of Moderate to Severe Coronavirus Disease (COVID-19) in Hospitalized Patients
- Conditions
- COVID-19
- Interventions
- Registration Number
- NCT04321993
- Lead Sponsor
- Lisa Barrett
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 363
- 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.
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Remdesivir + baricitinib Remdesivir (antiviral) + barictinib (janus kinase inhibitor) Moderate and severe, not critical disease Remdesivir Remdesivir (antiviral) Moderate and severe, not critical disease Tocilizumab Tocilizumab (interleukin 6 inhibitor) Severe, critical disease Baricitinib Baricitinib (janus kinase inhibitor) Moderate and severe, not critical disease
- Primary Outcome Measures
Name Time Method Clinical status of subject at day 15 (on a 7 point ordinal scale). Up to 15 days 1. Not hospitalized, no limitations on activities
2. Not hospitalized, limitation on activities;
3. Hospitalized, not requiring supplemental oxygen;
4. Hospitalized, requiring supplemental oxygen;
5. Hospitalized, on non-invasive ventilation or high flow oxygen devices;
6. Hospitalized, on invasive mechanical ventilation or ECMO;
7. Death.
- Secondary Outcome Measures
Name Time Method 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.
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
Number of participants that developed Acute Respiratory Distress Syndrome (ARDS) after treatment Up to 24 weeks Cause of death (if applicable) Up to 24 weeks 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.
Status on an ordinal scale assessed daily while hospitalized and on days 15 and 29 and 180. Up to 180 days 1. Not hospitalized, no limitations on activities
2. Not hospitalized, limitation on activities;
3. Hospitalized, not requiring supplemental oxygen;
4. Hospitalized, requiring supplemental oxygen;
5. Hospitalized, on non-invasive ventilation or high flow oxygen devices;
6. Hospitalized, on invasive mechanical ventilation or ECMO;
7. Death.Number of participants with normal pulmonary function and normal O2 saturation on days 11, 15 and 29 Up to 29 days Duration of supplemental oxygen (if applicable) Up to 29 days Duration of mechanical ventilation (if applicable) Up to 29 days Adverse events Up to 180 days Sequential Organ Failure Assessment (SOFA) score, daily while hospitalized and on days 15 and 29. (Initial, highest, deltas and mean) Up to 29 days Duration of hospitalization Up to 29 days
Trial Locations
- Locations (1)
Nova Scotia Health Authority
🇨🇦Halifax, Nova Scotia, Canada