Tocilizumab vs CRRT in Management of Cytokine Release Syndrome (CRS) in COVID-19
- Conditions
- Covid-19Cytokine StormTocilizumabCytokine Release SyndromeSARS
- Interventions
- Registration Number
- NCT04306705
- Lead Sponsor
- Tongji Hospital
- Brief Summary
Some patients infected with the COVID-19 can develop uncontrolled immune response, leading to potentially life-threatening damage to lung tissue. Tocilizumab was first approved by the U.S. FDA in 2010 for rheumatoid arthritis and might now be used to treat serious COVID-19 patients with lung damage, according to China's National Health Commission updated its treatment guidelines in 7th version.Continuous Renal Replacement Therapy (CRRT) was recommended by China's National Health Commission treatment guidelines in 1st-7th version to control sever COVID-19 patients.
- Detailed Description
Tocilizumab doesn't directly kill the novel coronavirus. It's known as an inhibitor of the receptor of interleukin 6 (IL-6), a pro-inflammatory cytokine. In the disease COVID-19, the body may respond to the pathogen by overproducing immune cells and their signaling molecules in a dangerous phenomenon called cytokine release storm.It has been recently speculated that IL-6 as a main culprit in that immune over activation among COVID-19 patients, hence the Tocilizumab clinical trial was initiated. In 2017, the FDA also approved Tocilizumab to treat cytokine release syndrome (CRS), a form of cytokine storm caused by CAR-T treatment. The investigator's hypothesis was that Tocilizumab would be associated with better clinical outcomes, such as decreased systemic inflammation, improved survival rate, better hemodynamic and improved of respiratory distress.Systemic inflammatory response syndrome was one of the main indications for treatment with CRRT. So it is clinically significant to compare the efficacy and safety of Tocilizumab and CRRT in management of CRS triggered by COVID-19.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 120
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Agrees to the collection of oropharyngeal or anal swabs and venous blood per protocol.
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Male or non-pregnant female adult ≥18 years of age at time of enrollment.
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Has laboratory-confirmed novel coronavirus infection as determined by polymerase chain reaction (PCR), or other commercial or public health assay in oropharyngeal or anal specimen within 72 hours prior to hospitalization.
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Illness of any duration, and at least one of the following:
- Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR
- Clinical assessment (evidence of rales/crackles on physical examination) AND SpO2 ≤93% on room air, OR
- Requiring mechanical ventilation and/or supplemental oxygen, OR
- Sustained fever in the past 24 hours and unresponsive to NSAID or steroid
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Serum IL-6 ≥3 times the upper limit of normal
- Alanine transaminase/aspartate transaminase (ALT/AST) > 5 times the upper limit of normal.
- Stage 4 severe chronic kidney disease or requiring dialysis (i.e. estimated glomerular filtration rate (eGFR) < 30 ml /min/1.73 m^2)
- Hemoglobin<80 g/L
- Leukocytes<2.0×10^9
- Platelets<50×10^9
- Pregnancy or breast feeding.
- Anticipated transfer to another hospital which is not a study site within 72 hours.
- Expected life span does not exceed 7 days.
- Allergy to any study medication.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Continuous Renal Replacement Therapy Continuous renal replacement therapy Femoral vein catheterization was performed to complete continuous renal replacement therapy for consecutive 3 times or more. Standard care Standard of care Standard of care therapy per local written policies or guidelines. Tocilizumab Standard of care Subjects received 8 mg/kg (body weight) Tocilizumab once in 100 ml 0.9% saline solution and administered intravenously within no less than 60 minutes. Tocilizumab was administered according to the local label. Continuous Renal Replacement Therapy Standard of care Femoral vein catheterization was performed to complete continuous renal replacement therapy for consecutive 3 times or more. Tocilizumab Tocilizumab Subjects received 8 mg/kg (body weight) Tocilizumab once in 100 ml 0.9% saline solution and administered intravenously within no less than 60 minutes. Tocilizumab was administered according to the local label.
- Primary Outcome Measures
Name Time Method Proportion of Participants With Normalization of Fever and Oxygen Saturation Through Day 14 First dose date up to 14 days This is a composite outcome measure. Criteria for fever normalization: Temperature \< 36.6 °C armpit, \< 37.2 °C oral sustained for at least 72 hours and criteria for oxygen normalization: peripheral capillary oxygen saturation (Sp02) \> 94% sustained for at least 72 hours.
- Secondary Outcome Measures
Name Time Method Change from baseline in white blood cell and differential count Day 1 through Day 28 Blood routine test
All-cause mortality up to 12 weeks Date and cause of death (if applicable).
Time to first negative in 2019 novel Corona virus RT-PCR test Up to 28 days Oropharyngeal or anal swabs
Change from baseline in hsCRP Day 1 through Day 28 Serum hsCRP
Change from baseline in cytokines IL-1β, IL-10, sIL-2R, IL-6, IL-8 and TNF-α Day 1 through Day 28 Serum inflammatory cytokines
Duration of hospitalization Up to 28 days Measured in days
Proportion of Participants With Normalization of Fever Through Day 14 First dose date up to 14 days Criteria for: Temperature \< 36.6 °C armpit, \< 37.2 °C oral, or \< 37.8 °C rectal sustained for at least 72 hours.
Change from baseline in proportion of CD4+CD3/CD8+CD3 T cells Day 1 through Day 28 (if applicable) Flow cytometry for peripheral whole blood
Trial Locations
- Locations (1)
Tongji Hospital
🇨🇳Wuhan, Hubei, China