Tocilizumab vs CRRT in Management of Cytokine Release Syndrome (CRS) in COVID-19

Tongji Hospital120 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

120

Conditions

Covid-19 SARS Cytokine Storm

Interventions

TocilizumabDRUG

Administered as an intravenous infusion.

Standard of careOTHER

Standard of care therapy per local written policies or guidelines and includes balancing of electrolytes and acid-base, the provision of enteral or parenteral nutrients support, antibiotics therapy, oxygen therapy and noninvasive ventilation.

Continuous renal replacement therapyPROCEDURE

Catheter insertion site is femoral vein.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Agrees to the collection of oropharyngeal or anal swabs and venous blood per protocol. 2. Male or non-pregnant female adult ≥18 years of age at time of enrollment. 3. 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. 4. Illness of any duration, and at least one of the following: 1. Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR 2. Clinical assessment (evidence of rales/crackles on physical examination) AND SpO2 ≤93% on room air, OR 3. Requiring mechanical ventilation and/or supplemental oxygen, OR 4. Sustained fever in the past 24 hours and unresponsive to NSAID or steroid 5. Serum IL-6 ≥3 times the upper limit of normal Exclusion Criteria: 1. Alanine transaminase/aspartate transaminase (ALT/AST) \> 5 times the upper limit of normal. 2. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. estimated glomerular filtration rate (eGFR) \< 30 ml /min/1.73 m\^2) 3. Hemoglobin\<80 g/L 4. Leukocytes\<2.0×10\^9 5. Platelets\<50×10\^9 6. Pregnancy or breast feeding. 7. Anticipated transfer to another hospital which is not a study site within 72 hours. 8. Expected life span does not exceed 7 days. 9. Allergy to any study medication.

Outcomes

Primary Outcomes

Proportion of Participants With Normalization of Fever and Oxygen Saturation Through Day 14

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.

Time frame: First dose date up to 14 days

Secondary Outcomes

Duration of hospitalization

Measured in days

Time frame: Up to 28 days

Proportion of Participants With Normalization of Fever Through Day 14

Criteria for: Temperature \< 36.6 °C armpit, \< 37.2 °C oral, or \< 37.8 °C rectal sustained for at least 72 hours.

Time frame: First dose date up to 14 days

Change from baseline in white blood cell and differential count

Blood routine test

Time frame: Day 1 through Day 28

Time to first negative in 2019 novel Corona virus RT-PCR test

Oropharyngeal or anal swabs

Time frame: Up to 28 days

All-cause mortality

Date and cause of death (if applicable).

Time frame: up to 12 weeks

Change from baseline in hsCRP

Serum hsCRP

Time frame: Day 1 through Day 28

Change from baseline in cytokines IL-1β, IL-10, sIL-2R, IL-6, IL-8 and TNF-α

Serum inflammatory cytokines

Time frame: Day 1 through Day 28

Change from baseline in proportion of CD4+CD3/CD8+CD3 T cells

Flow cytometry for peripheral whole blood

Time frame: Day 1 through Day 28 (if applicable)

Tocilizumab vs CRRT in Management of Cytokine Release Syndrome (CRS) in COVID-19

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts