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

NCT04361552 | Withdrawn Phase 3 DMC FDA Drug

• 4 other identifiers: STUDY00000419NCI-2020-02314WINSHIP4998-20P30CA138292
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 7 days

• 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.

  Up to 30-day after randomization

Secondary Outcomes (5)

• Rate of intensive care (ICU) transfer

  Up to 2 years

• Rate of invasive mechanical ventilation

  Up to 2 years

• Rate of tracheostomy

  Up to 2 years

• Length of ICU stay

  Up to 2 years

• Length of hospital stay

  Up 2 years

Study Arms (2)

Arm I (tocilizumab, standard of care)

EXPERIMENTAL

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; Biological: Tocilizumab

Arm II (standard of care)

ACTIVE COMPARATOR

Patients receive standard of care.

Other: Best Practice

Interventions

Best Practice OTHER

Receive standard of care

Also known as: standard of care, standard therapy

Arm I (tocilizumab, standard of care); Arm II (standard of care)

Tocilizumab BIOLOGICAL

Given IV

Also known as: 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

Arm I (tocilizumab, standard of care)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Stroke; Pulmonary Disease, Chronic Obstructive; Kidney Failure, Chronic; Coronary Artery Disease; Diabetes Mellitus; Neoplasms; COVID-19

Interventions

Practice Guidelines as Topic; Standard of Care; tocilizumab; Immunoglobulin G; Disulfides

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Intervention Hierarchy (Ancestors)

Guidelines as Topic; Quality Assurance, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality Indicators, Health Care; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Ajay K Nooka

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 7, 2020
• First Posted: April 24, 2020
• Study Start: April 7, 2020
• Primary Completion: June 2, 2020
• Study Completion: June 2, 2020
• Last Updated: June 18, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)