Tocilizumab for the Treatment of Cytokine Release Syndrome in Patients With COVID-19 (SARS-CoV-2 Infection)

• ClinicalTrials.gov Identifier: NCT04361552
• Recruitment Status: Withdrawn
• First Posted: April 24, 2020
• Last Update Posted: June 18, 2020
• Sponsor: Emory University
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Ajay Nooka, Emory University

Tracking Information

• First Submitted Date: April 7, 2020
• First Posted Date: April 24, 2020
• Last Update Posted Date: June 18, 2020
• Actual Study Start Date: April 7, 2020
• Actual Primary Completion Date: June 2, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 22, 2020)

• 7-day length of invasive mechanical ventilation (MV) [ Time Frame: Up to 7 days ]
  The 7-day length of invasive MV for each arm will be estimated with 95% confidence intervals (CIs) using the exact binomial distribution. Their difference by the arms will be tested by Cochran-Mantel-Haenszel (CMH) test stratified by the age group and Sequential Organ Failure Assessment (SOFA) score at significance level of 0.05.
• 30-day mortality rate [ Time Frame: Up to 30-day after randomization ]
  Defined as death within 30-day after randomization. The 30-day mortality rate for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 22, 2020)

• Rate of intensive care (ICU) transfer [ Time Frame: Up to 2 years ]
  The rate of ICU transfer for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.
• Rate of invasive mechanical ventilation [ Time Frame: Up to 2 years ]
  The rate of invasive mechanical ventilation for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.
• Rate of tracheostomy [ Time Frame: Up to 2 years ]
  The rate of tracheostomy for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.
• Length of ICU stay [ Time Frame: Up to 2 years ]
  Will first be described by median and inter-quartile, and then compared between two arms by Wilcoxon Sum-Rank test
• Length of hospital stay [ Time Frame: Up 2 years ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Tocilizumab for the Treatment of Cytokine Release Syndrome in Patients With COVID-19 (SARS-CoV-2 Infection)
• Official Title: Tociluzumab for Cytokine Release Syndrome With SARS-CoV-2: An Open-Labeled, Randomized Phase 3 Trial
• Brief Summary: This phase III trial compares the effect of adding tocilizumab to standard of care versus standard of care alone in treating cytokine release syndrome (CRS) in patients with SARS-CoV-2 infection. CRS is a potentially serious disorder caused by the release of an excessive amount of substance that is made by cells of the immune system (cytokines) as a response to viral infection. Tocilizumab is used to decrease the body's immune response. Adding tocilizumab to standard of care may work better in treating CRS in patients with SARS-CoV-2 infection compared to standard of care alone.

Detailed Description

PRIMARY OBJECTIVE:

I. To decrease the length of invasive mechanical ventilation (MV) and rate of 30-day mortality from CRS due to SARS-CoV-2.

SECONDARY OBJECTIVES:

I. To decrease the rates of intensive care unit (ICU) transfer. II. To decrease the rate of invasive mechanical ventilation (MV). III. To decrease the length of ICU stay. IV. To decrease the rate of tracheostomy. V. Safety and efficacy of tociluzumab. VI. Biomarker assessment for response.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive tocilizumab intravenously (IV) every 12 hours for up to 3 doses in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care.

ARM II: Patients receive standard of care.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Cerebrovascular Accident
• Chronic Obstructive Pulmonary Disease
• Chronic Renal Failure
• Coronary Artery Disease
• Diabetes Mellitus
• Malignant Neoplasm
• SARS Coronavirus 2 Infection

Intervention

• Other: Best Practice
  Receive standard of care
  Other Names:

  • standard of care
  • standard therapy
• Biological: Tocilizumab
  Given IV
  Other Names:

  • Actemra
  • Immunoglobulin G1, Anti-(Human Interleukin 6 Receptor) (Human-Mouse Monoclonal MRA Heavy Chain), Disulfide with Human-Mouse Monoclonal MRA Kappa-Chain, Dimer
  • MRA
  • R-1569
  • RoActemra

Study Arms

• Experimental: Arm I (tocilizumab, standard of care)
  Patients receive tocilizumab IV every 12 hours for up to 3 doses in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care.
  Interventions:

  • Other: Best Practice
  • Biological: Tocilizumab
• Active Comparator: Arm II (standard of care)
  Patients receive standard of care.
  Intervention: Other: Best Practice

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: June 16, 2020): 0
• Original Estimated Enrollment (submitted: April 22, 2020): 180
• Actual Study Completion Date: June 2, 2020
• Actual Primary Completion Date: June 2, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis with SARS-CoV-2 by the currently available assays (Food and Drug Administration [FDA] approved)

• Should be hospitalized and exhibit at least one of the following predictors of mortality

  • Age >= 65 years
  • Current smoker (smoked >= 100 cigarettes in life and actively smoking)
  • Chronic obstructive pulmonary disease (COPD)
  • Diabetes
  • Hypertension
  • Coronary artery disease
  • Cerebrovascular accident (CVA)
  • Chronic renal disease (creatinine of >= 2 mg/dl)
  • Cancer
  • Patients that have C-reactive protein (CRP) >= 10 mg/L
  • D-dimer >= 0.5 mg/L
  • Procalcitonin >= 0.5 mg/L
  • Lactate dehydrogenase (LDH) >= upper limit of normal (ULN)
• Patients or authorized family member willing to sign informed consent to participate in this study

Exclusion Criteria:

• Pregnant or lactating women
• Hypersensitivity to tocilizumab
• Patients or authorized family member unwilling to sign informed consent to participate in this study
• Uncontrolled tuberculosis, or any uncontrolled fungal infection (eg: candidemia)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04361552
• Other Study ID Numbers: STUDY00000419; NCI-2020-02314 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); WINSHIP4998-20 ( Other Identifier: Emory University Hospital/Winship Cancer Institute ); P30CA138292 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Results of the trial and not individual patient data will be shared. The study protocol, consent, and investigator's brochure will be available. The statistical plan is incorporated into the protocol, along with inclusion and exclusion criteria.

• Responsible Party: Ajay Nooka, Emory University
• Study Sponsor: Emory University
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ajay K Nooka; Emory University Hospital/Winship Cancer Institute

• PRS Account: Emory University
• Verification Date: June 2020