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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

Tracking Information
First Submitted Date  ICMJE June 5, 2020
First Posted Date  ICMJE June 9, 2020
Last Update Posted Date July 22, 2020
Estimated Study Start Date  ICMJE July 30, 2020
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2020)
All-cause mortality [ Time Frame: Assessed at 30 days post treatment ]
Mortality status of participants
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2020)
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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tocilizumab in Coronavirus-19 Positive Patients
Official Title  ICMJE 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
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%.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Covid19
  • COVID-19
  • Severe Acute Respiratory Syndrome Coronavirus 2
  • Coronavirus
  • Inflammation
Intervention  ICMJE 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
Study Arms  ICMJE
  • 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.
    Intervention: Biological: Tocilizumab
  • 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.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 5, 2020)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jacinda R Larson, PhD 4039555537 jacinda.larson@albertahealthservices.ca
Contact: Namneet Sandhu, MPH namneet.sandhu@ucalgary.ca
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04423042
Other Study ID Numbers  ICMJE REB20-0713
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Results will be rapidly published.
Responsible Party University of Calgary
Study Sponsor  ICMJE University of Calgary
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Susanne Benseler, MD PhD University of Calgary
PRS Account University of Calgary
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP