Clinical trial NCT04306705: Tocilizumab vs CRRT in Management of Cytokine Release Syndrome (CRS) in COVID-19
Official title: A Retrospective Study of Evaluating Safety and Efficacy of Tocilizumab Compared to Continuous Renal Replacement Therapy in Controlling CRS Triggered by COVID-19
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Covid-19
SARS
Cytokine Storm
Cytokine Release Syndrome
Tocilizumab
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
Collaborators: name: Hubei Xinhua Hospital
name: Wuhan No.1 Hospital
name: Wuhan Central Hospital
First posted: 2020-03-13
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Laboratory (RT-PCR) confirmed infection with 2019-nCoV. Lung involvement confirmed with chest imaging Hospitalized with a SaO2/SPO2≤93% on room air or Pa02/Fi02 ratio \<300mmHg and ≤14 days since illness onset.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of Participants With Normalization of Fever and Oxygen Saturation Through Day 14
timeFrame: First dose date up to 14 days
Secondary outcomes:
measure: Duration of hospitalization
timeFrame: Up to 28 days
measure: Proportion of Participants With Normalization of Fever Through Day 14
timeFrame: First dose date up to 14 days
measure: Change from baseline in white blood cell and differential count
timeFrame: Day 1 through Day 28
measure: Time to first negative in 2019 novel Corona virus RT-PCR test
timeFrame: Up to 28 days
measure: All-cause mortality
timeFrame: up to 12 weeks
measure: Change from baseline in hsCRP
timeFrame: Day 1 through Day 28
measure: Change from baseline in cytokines IL-1β, IL-10, sIL-2R, IL-6, IL-8 and TNF-α
timeFrame: Day 1 through Day 28
measure: Change from baseline in proportion of CD4+CD3/CD8+CD3 T cells
timeFrame: Day 1 through Day 28 (if applicable)
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
Study officials:
affiliation: Tongji Hospital
name: SHAOXIAN HU, M.D
role: STUDY_DIRECTOR
References: