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

Tongji Hospital

Status: Unknown

Conditions: Cytokine Release Syndrome; Tocilizumab; Cytokine Storm; Covid-19; SARS

Treatments: Procedure: Continuous renal replacement therapy; Other: Standard of care; Drug: Tocilizumab

Study type: Observational

Funder types: Other

Identifiers

NCT04306705

WHTJCOVID-19

Details and patient eligibility

About

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.

Full 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

120 participants in 3 patient groups

Tocilizumab

Description:

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.

Treatment:

Drug: Tocilizumab

Other: Standard of care

Continuous Renal Replacement Therapy

Description:

Femoral vein catheterization was performed to complete continuous renal replacement therapy for consecutive 3 times or more.

Treatment:

Procedure: Continuous renal replacement therapy

Other: Standard of care

Standard care

Description:

Standard of care therapy per local written policies or guidelines.

Treatment:

Other: Standard of care