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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04321993
Recruitment Status : Recruiting
First Posted : March 26, 2020
Last Update Posted : March 24, 2022
Sponsor:
Collaborators:
Nova Scotia Health Authority
Dalhousie University
Information provided by (Responsible Party):
Lisa Barrett, Nova Scotia Health Authority

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.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Baricitinib (janus kinase inhibitor) Drug: Remdesivir (antiviral) + barictinib (janus kinase inhibitor) Drug: Remdesivir (antiviral) Drug: Tocilizumab (interleukin 6 inhibitor) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 800 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Moderate to Severe Coronavirus Disease (COVID-19) in Hospitalized Patients
Actual Study Start Date : April 17, 2020
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.

Experimental: 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).

Experimental: 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.


Experimental: 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.

No Intervention: Clinical standard of care
Moderate and severe, not critical disease AND severe, critical disease as applicable



Primary Outcome Measures :
  1. Clinical status of subject at day 15 (on a 7 point ordinal scale). [ Time Frame: 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 :
  1. Status on an ordinal scale assessed daily while hospitalized and on days 15 and 29 and 180. [ Time Frame: 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.

  2. Length of time to clinical improvement [ Time Frame: 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.

  3. Number of participants with normal pulmonary function and normal O2 saturation on days 11, 15 and 29 [ Time Frame: Up to 29 days ]
  4. Number of participants that developed Acute Respiratory Distress Syndrome (ARDS) after treatment [ Time Frame: Up to 24 weeks ]
  5. Length of time to clinical progression [ Time Frame: Up to 29 days ]
    Time to clinical progression, defined as the time to death, mechanical ventilation, or ICU admission

  6. Cause of death (if applicable) [ Time Frame: Up to 24 weeks ]
  7. 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 ]
  8. Length of time to normalization of fever [ Time Frame: 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

  9. Length of time to normalization of oxygen saturation [ Time Frame: Up to 29 days ]
    Oxygen normalization as defined by: peripheral capillary oxygen saturation (Sp02) > 94% sustained minimum 24 hours.

  10. Duration of supplemental oxygen (if applicable) [ Time Frame: Up to 29 days ]
  11. Duration of mechanical ventilation (if applicable) [ Time Frame: Up to 29 days ]
  12. Duration of hospitalization [ Time Frame: Up to 29 days ]
  13. Adverse events [ Time Frame: Up to 180 days ]

Other Outcome Measures:
  1. 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 ]
  2. 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 ]
  3. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

  • 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:

  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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04321993


Contacts
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Contact: Barbara Goodall (902) 292-0132 barbara.goodall@nshealth.ca
Contact: Lisa Barrett (902) 473-6446 lisa.barrett@nshealth.ca

Locations
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Canada, Nova Scotia
Nova Scotia Health Authority Recruiting
Halifax, Nova Scotia, Canada, B3H 1V7
Contact: Lisa Barrett, MD       lisa.barrett@nshealth.ca   
Contact: Barbara Goodall       barbara.goodall@nshealth.ca   
Sponsors and Collaborators
Lisa Barrett
Nova Scotia Health Authority
Dalhousie University
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Responsible Party: Lisa Barrett, Clinician Scientist, Nova Scotia Health Authority
ClinicalTrials.gov Identifier: NCT04321993    
Other Study ID Numbers: SAIL-004
First Posted: March 26, 2020    Key Record Dates
Last Update Posted: March 24, 2022
Last Verified: March 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Lisa Barrett, Nova Scotia Health Authority:
COVID
coronavirus
SARS-CoV-2
Additional relevant MeSH terms:
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COVID-19
Coronavirus Infections
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Antiviral Agents
Remdesivir
Janus Kinase Inhibitors
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors