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

Sponsor

Emory University (Other)

Overall Status

Withdrawn

CT.gov ID

NCT04361552

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arms

1.8

Actual Duration (Months)

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Cerebrovascular Accident Chronic Obstructive Pulmonary Disease Chronic Renal Failure Coronary Artery Disease Diabetes Mellitus Malignant Neoplasm SARS Coronavirus 2 Infection	Other: Best Practice Biological: Tocilizumab	Phase 3

Detailed Description

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Tociluzumab for Cytokine Release Syndrome With SARS-CoV-2: An Open-Labeled, Randomized Phase 3 Trial

Actual Study Start Date :

Apr 7, 2020

Actual Primary Completion Date :

Jun 2, 2020

Actual Study Completion Date :

Jun 2, 2020

Arms and Interventions

Arm	Intervention/Treatment
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.	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
Active Comparator: Arm II (standard of care) Patients receive standard of care.	Other: Best Practice Receive standard of care Other Names: standard of care standard therapy

Arm

Intervention/Treatment

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.

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

Active Comparator: Arm II (standard of care)

Patients receive standard of care.

Other: Best Practice

Receive standard of care

Other Names:

standard of care

standard therapy

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Rate of intensive care (ICU) transfer [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 [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 [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 [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 [Up 2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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)