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

Primary Purpose

Cerebrovascular Accident, Chronic Obstructive Pulmonary Disease, Chronic Renal Failure

Status
Withdrawn
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Best Practice
Tocilizumab
Sponsored by
Emory University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cerebrovascular Accident

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Emory University Hospital/Winship Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm I (tocilizumab, standard of care)

Arm II (standard of care)

Arm Description

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.

Patients receive standard of care.

Outcomes

Primary Outcome Measures

7-day length of invasive mechanical ventilation (MV)
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
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.

Secondary Outcome Measures

Rate of intensive care (ICU) transfer
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
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
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
Will first be described by median and inter-quartile, and then compared between two arms by Wilcoxon Sum-Rank test
Length of hospital stay

Full Information

First Posted
April 7, 2020
Last Updated
June 16, 2020
Sponsor
Emory University
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04361552
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Study abandoned due to drug billing issues
Study Start Date
April 7, 2020 (Actual)
Primary Completion Date
June 2, 2020 (Actual)
Study Completion Date
June 2, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cerebrovascular Accident, Chronic Obstructive Pulmonary Disease, Chronic Renal Failure, Coronary Artery Disease, Diabetes Mellitus, Malignant Neoplasm, SARS Coronavirus 2 Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (tocilizumab, standard of care)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm II (standard of care)
Arm Type
Active Comparator
Arm Description
Patients receive standard of care.
Intervention Type
Other
Intervention Name(s)
Best Practice
Other Intervention Name(s)
standard of care, standard therapy
Intervention Description
Receive standard of care
Intervention Type
Biological
Intervention Name(s)
Tocilizumab
Other Intervention Name(s)
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
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
7-day length of invasive mechanical ventilation (MV)
Description
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.
Time Frame
Up to 7 days
Title
30-day mortality rate
Description
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.
Time Frame
Up to 30-day after randomization
Secondary Outcome Measure Information:
Title
Rate of intensive care (ICU) transfer
Description
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.
Time Frame
Up to 2 years
Title
Rate of invasive mechanical ventilation
Description
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.
Time Frame
Up to 2 years
Title
Rate of tracheostomy
Description
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.
Time Frame
Up to 2 years
Title
Length of ICU stay
Description
Will first be described by median and inter-quartile, and then compared between two arms by Wilcoxon Sum-Rank test
Time Frame
Up to 2 years
Title
Length of hospital stay
Time Frame
Up 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ajay K Nooka
Organizational Affiliation
Emory University Hospital/Winship Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory University Hospital/Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing 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.

Learn more about this trial

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

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