Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04361552
Recruitment Status : Withdrawn (Study abandoned due to drug billing issues)
First Posted : April 24, 2020
Last Update Posted : June 18, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Ajay Nooka, Emory University

Tracking Information
First Submitted Date  ICMJE April 7, 2020
First Posted Date  ICMJE April 24, 2020
Last Update Posted Date June 18, 2020
Actual Study Start Date  ICMJE April 7, 2020
Actual Primary Completion Date June 2, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  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 for the Treatment of Cytokine Release Syndrome in Patients With COVID-19 (SARS-CoV-2 Infection)
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cerebrovascular Accident
  • Chronic Obstructive Pulmonary Disease
  • Chronic Renal Failure
  • Coronary Artery Disease
  • Diabetes Mellitus
  • Malignant Neoplasm
  • SARS Coronavirus 2 Infection
Intervention  ICMJE
  • 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  ICMJE
  • 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

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 Withdrawn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

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04361552
Other Study ID Numbers  ICMJE 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  ICMJE
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  ICMJE Emory University
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Ajay K Nooka Emory University Hospital/Winship Cancer Institute
PRS Account Emory University
Verification Date June 2020

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