Treatment of Moderate to Severe Coronavirus Disease (COVID-19) in Hospitalized Patients
Latest Information Update: 20 Sep 2023
At a glance
- Drugs Baricitinib (Primary)
- Indications Adult respiratory distress syndrome; COVID 2019 infections; Respiratory tract infections
- Focus Therapeutic Use
- 15 Sep 2023 Planned End Date changed from 1 Sep 2023 to 1 Apr 2024.
- 15 Sep 2023 Planned primary completion date changed from 1 Apr 2023 to 1 Apr 2024.
- 14 Mar 2023 Planned End Date changed from 1 Mar 2023 to 1 Sep 2023.
Most Recent Events
Trial Overview
Purpose
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.
Primary Endpoints
Clinical status of subject at day 15 (on a 7 point ordinal scale).
description: 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.
time_frame: Up to 15 days
Other Endpoints
Status on an ordinal scale assessed daily while hospitalized and on days 15 and 29 and 180.
description: 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.
time_frame: Up to 180 days
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
Number of participants with normal pulmonary function and normal O2 saturation on days 11, 15 and 29
time_frame: Up to 29 days
Number of participants that developed Acute Respiratory Distress Syndrome (ARDS) after treatment
time_frame: Up to 24 weeks
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
Cause of death (if applicable)
time_frame: Up to 24 weeks
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
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
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
Duration of supplemental oxygen (if applicable)
time_frame: Up to 29 days
Duration of mechanical ventilation (if applicable)
time_frame: Up to 29 days
Duration of hospitalization
time_frame: Up to 29 days
Adverse events
time_frame: Up to 180 days
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
Percent of subjects with SARS-CoV-2 detectable in blood at days 3, 5, 8, 11, 15, 29 and 180.
time_frame: Up to 180 days
Quantitative SARS-CoV-2 viral load in blood at days 3, 5, 8, and 11, 15, 29, and 180.
time_frame: Up to 180 days [1]
Diseases Treated
| Indication | Qualifiers | Patient Segments |
|---|---|---|
| Adult respiratory distress syndrome | treatment | - |
| COVID 2019 infections | treatment | - |
| Respiratory tract infections | treatment | moderate, severe |
Subjects
- Subject Type patients
-
Number
Planned: 800
Actual: 363
- Sex male & female
- Age Group ≥ 18 years; adult
Patient 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.
Patient 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)
Trial Details
Identifiers
| Identifier | Owner |
|---|---|
| NCT04321993 | ClinicalTrials.gov: US National Institutes of Health |
| SAIL004 | - |
Trial Dates
-
Initiation Dates
Planned : 01 Apr 2020
Actual : 17 Apr 2020
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Primary Completion Dates
Planned : 01 Apr 2024
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End Dates
Planned : 01 Apr 2024
Other Details
- Design open; parallel; prospective
- Phase of Trial Phase II
- Location Canada
- Focus Therapeutic Use
Interventions
| Drugs | Route | Formulation |
|---|---|---|
| BaricitinibPrimary Drug | Oral | Tablet |
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.)
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.)
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).)
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.)
Clinical standard of care
Moderate and severe, not critical disease AND severe, critical disease as applicable
Trial Centres
Investigators
| Investigator | Centre Name | Trial Centre Country |
|---|---|---|
|
Barbara Goodall
(902) 292-0132 barbara.goodall@nshealth.ca
show details
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Lisa Barrett
(902) 473-6446 lisa.barrett@nshealth.ca
show details
|
-
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Centres
| Centre Name | Location | Trial Centre Country |
|---|---|---|
| - |
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| Dalhousie University |
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| Lisa Barrett |
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| Nova Scotia Health Authority |
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| Nova Scotia Health Authority | Halifax, Nova Scotia | Canada |
Trial History
| Event Date | Event Type | Comment |
|---|---|---|
| 20 Sep 2023 | Other trial event | Last checked against the ClinicalTrials.gov record. Updated 20 Sep 2023 |
| 15 Sep 2023 | Completion date | Planned End Date changed from 1 Sep 2023 to 1 Apr 2024. Updated 20 Sep 2023 |
| 15 Sep 2023 | Other trial event | Planned primary completion date changed from 1 Apr 2023 to 1 Apr 2024. Updated 20 Sep 2023 |
| 14 Mar 2023 | Completion date | Planned End Date changed from 1 Mar 2023 to 1 Sep 2023. Updated 16 Mar 2023 |
| 14 Mar 2023 | Other trial event | Planned primary completion date changed from 1 Feb 2023 to 1 Apr 2023. Updated 16 Mar 2023 |
| 14 Mar 2023 | Status change - active, no longer recruiting | Status changed from recruiting to active, no longer recruiting. Updated 16 Mar 2023 |
| 09 Mar 2022 | Completion date | Planned End Date changed from 1 Mar 2022 to 1 Mar 2023. Updated 25 Mar 2022 |
| 09 Mar 2022 | Other trial event | Planned primary completion date changed from 1 Feb 2022 to 1 Feb 2023. Updated 25 Mar 2022 |
| 22 Jul 2020 | Protocol amendment | Number of arms changed from 3 to 2. Drug Lopinavir/ritonavir and experimental arm: Lopinavir/ritonavir removed from study protocol. Planned number of subjects also decreased. Updated 27 Jul 2020 |
| 22 Jul 2020 | Other trial event | Planned number of patients changed from 1000 to 800. Updated 27 Jul 2020 |
| 02 Jul 2020 | Protocol amendment | Number of arms changed from 4 to 3. Drug Hydroxychloroquine sulfate and experimental arm: Hydroxychloroquine sulfate removed from study protocol. Updated 27 Jul 2020 |
| 15 May 2020 | Completion date | Planned End Date changed from 1 Jul 2021 to 1 Mar 2022. Updated 20 May 2020 |
| 15 May 2020 | Other trial event | Planned primary completion date changed from 1 Feb 2021 to 1 Feb 2022. Updated 20 May 2020 |
| 22 Apr 2020 | Status change - recruiting | Status changed from not yet recruiting to recruiting. Updated 27 Apr 2020 |
| 04 Apr 2020 | Other trial event | Planned initiation date changed from 1 Mar 2020 to 1 Apr 2020. Updated 08 Apr 2020 |
| 31 Mar 2020 | New trial record | New trial record Updated 31 Mar 2020 |
References
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ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2023;.
Available from: URL: http://clinicaltrials.gov
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