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Tocilizumab in Coronavirus-19 Positive Patients

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ClinicalTrials.gov Identifier: NCT04423042
Recruitment Status : Not yet recruiting
First Posted : June 9, 2020
Last Update Posted : July 22, 2020
Sponsor:
Information provided by (Responsible Party):
University of Calgary

Study Description
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Brief Summary:
This is a cohort study of COVID-19 patients with hyperinflammation. It aims to determine the impact of adjunctive Tocilizumab (TCZ) to standard of care on the reduction of hyperinflammation-related mortality in COVID-19. Patients with COVID-19 are at high risk of life-threatening hyperinflammation and death. One in three COVID-19 patients admitted to ICU was found to develop life-threatening hyperinflammation. The risk of death when untreated is estimated to be 50-80%.

Condition or disease Intervention/treatment Phase
Covid19 COVID-19 Severe Acute Respiratory Syndrome Coronavirus 2 Coronavirus Inflammation Biological: Tocilizumab Phase 3

Detailed Description:

The novel coronavirus, SARS-Cov2/COVID-19, emerged in late 2019 in Wuhan, China. Quickly, SARS-CoV2 spread to all corners of the globe. In March 2020, The World Health Organization (WHO) declared SARS-CoV2/COVID-19 a pandemic. Individuals infected with SARS-CoV2 have a varied clinical presentation, ranging from asymptomatic or mild respiratory symptoms to severe involvement of the lower respiratory tract, with patients requiring mechanical ventilation. A particular point of interest is how the overall severity and clinical outcomes of COVID-19 patients may be associated with the excessive production of pro-inflammatory cytokines, or hyperinflammation, leading to acute respiratory distress syndrome. This state of hyperinflammation may be associated with increased mortality in COVID-19 patients. Tocilizumab, an Interleukin-6 antagonist, may help treat COVID-19 associated hyperinflammation.

This is a nested interventional cohort study of COVID-19 patients with hyperinflammation. It aims to determine the impact of adjunctive Tocilizumab (TCZ) to standard of care on the reduction of hyperinflammation-related mortality in COVID-19. Patients with COVID-19 are at high risk of life-threatening hyperinflammation and death. One in three COVID-19 patients admitted to ICU was found to develop life-threatening hyperinflammation. The risk of death when untreated is estimated to be 50-80%. TCZ treatment may reduce mortality.

Primary objective: To establish that tocilizumab, in addition to standard of care, reduces the 30-day mortality from hyperinflammation in COVID-19 disease significantly compared to no anti-interleukin therapy plus standard of care.

Secondary objectives: To evaluate the addition of tocilizumab therapy to standard of care on a number of secondary outcomes.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Nested Interventional Cohort Study to Assess the Efficacy and Safety of Adjunctive Humanized Monoclonal Interleukin-6 Receptor Blocker Tocilizumab (TCZ) Therapy to Standard of Care for the Reduction of Hyperinflammation Related Mortality in SARS-Cov2 Positive Patients
Estimated Study Start Date : July 30, 2020
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Tocilizumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Tocilizumab Arm
Tocilizumab 8 mg/kg IV up to a maximum of 800 mg with possible repetition of the same dosage within 28 hours (the optional second dose after 12 hours but before 28 hours following the first dose), based on the clinical judgement of the attending physician in consultation with the COVID-inflammation team.
 Biological: Tocilizumab
Tocilizumab binds to both soluble and membrane-bound interleukin-6 receptors and has been shown to inhibit interleukin 6-mediated signalling.
Other Name: Actemra
No Intervention: No Intervention Arm
No intervention arm patients will be identified from medical records, as being COVID-19 positive patients with hyperinflammation who did not receive any interleukin antagonist treatment.


Outcome Measures
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Primary Outcome Measures :
  1. All-cause mortality [ Time Frame: Assessed at 30 days post treatment ]
    Mortality status of participants


Secondary Outcome Measures :
  1. Ordinal Scale for evaluating subject clinical status at days 3, 8, 15, 30, 60 post treatment. [ Time Frame: Assessed at days 3, 8, 15, 30, 60 post treatment ]
    Uninfected, ambulatory, hospitalized: mild disease, hospitalized: severe disease, death


Eligibility Criteria
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Information from the National Library of Medicine

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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:

  1. Age ≥ 18 years
  2. All genders
  3. Hospitalization for suspected or confirmed SARS-CoV2 infection. COVID-19 diagnosis defined as positive on reverse-transcriptase polymerase chain reaction, with provincial laboratory confirmation.

  4. Signs of hyperinflammation (cytokine release syndrome) defined by the presence of any of the following:

    i. Elevated C-reactive protein (≥70 mg/dl and/or rising since last 24h not due to bacterial infection), ii. Ferritin (>700 mcg/L and/or rising since last 24h),

  5. Anti-interleukin treatment indication as per hyperinflammation team
  6. Informed consent for participation in the study

Exclusion Criteria:

  1. Goal of Care C (palliative care)
  2. Known hypersensitivity to TCZ or its components
  3. Current systemic immunosuppressive therapy; anti-interleukin 1 or anti-interleukin 6 treatment
  4. Known active bacterial or fungal infections or other clinical conditions that contraindicate TCZ and cannot be treated or resolved according to the physician's judgment
  5. Current or history of bowel perforation or diverticulitis
  6. Suspicion of active or latent tuberculosis
  7. Pregnant or breastfeeding patient
  8. Patients with known prior liver disease
Contacts and Locations
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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): NCT04423042


Contacts
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Contact: Jacinda R Larson, PhD 4039555537 jacinda.larson@albertahealthservices.ca
Contact: Namneet Sandhu, MPH namneet.sandhu@ucalgary.ca

Sponsors and Collaborators
University of Calgary
Investigators
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Principal Investigator: Susanne Benseler, MD PhD University of Calgary
More Information
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Additional Information:

Publications:

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Responsible Party: University of Calgary
ClinicalTrials.gov Identifier: NCT04423042    
Other Study ID Numbers: REB20-0713
First Posted: June 9, 2020    Key Record Dates
Last Update Posted: July 22, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Results will be rapidly published.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Coronavirus Infections
Severe Acute Respiratory Syndrome
Inflammation
Pathologic Processes
Coronaviridae Infections
 Nidovirales Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases