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

Phase 3

Withdrawn

• Conditions: SARS Coronavirus 2 Infection; Chronic Obstructive Pulmonary Disease; Chronic Renal Failure; Coronary Artery Disease; Diabetes Mellitus; Cerebrovascular Accident; Malignant Neoplasm
• Interventions: Other: Best Practice; Biological: Tocilizumab

• Registration Number: NCT04361552
• Lead Sponsor: Emory University

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2020-04-07
• Study First Submitted: 2020-04-07
• Study First Submitted QC: 2020-04-22
• Study First Posted: 2020-04-24
• Status Verified: 2020-06
• Primary Completion: 2020-06-02
• Study Completion: 2020-06-02
• Last Update Submitted: 2020-06-16
• Last Update Posted: 2020-06-18

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (tocilizumab, standard of care)	Best Practice	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 I (tocilizumab, standard of care)	Tocilizumab	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 II (standard of care)	Best Practice	Patients receive standard of care.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Length of hospital stay	Up 2 years
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 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 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

Trial Locations

Locations (1)

Emory University Hospital/Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States