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

Covid-19 Clinical Trial

— TACOS  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04306705
• Other study ID #: WHTJCOVID-19
• Status: Recruiting
• Start date: February 20, 2020
• Est. completion date: June 20, 2020

Study information

• Verified date: March 2020
• Source: Tongji Hospital
• Contact: YIKAI YU, M.D
• Phone: +1 (484) 995-5917
• Email: yuyikai[@]163.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: June 20, 2020
• Est. primary completion date: May 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Covid-19
• Cytokine Release Syndrome
• Cytokine Storm
• SARS
• Syndrome
• Tocilizumab

Intervention

Drug:
• Tocilizumab
Administered as an intravenous infusion.

Other:
• Standard of care
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.

Procedure:
• Continuous renal replacement therapy
Catheter insertion site is femoral vein.

Locations

Country	Name	City	State
China	Tongji Hospital	Wuhan	Hubei

Sponsors (4)

Lead Sponsor	Collaborator
Tongji Hospital	Hubei Xinhua Hospital, Wuhan central hospital, Wuhan No.1 Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	First dose date up to 14 days
Secondary	Duration of hospitalization	Measured in days	Up to 28 days
Secondary	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.	First dose date up to 14 days
Secondary	Change from baseline in white blood cell and differential count	Blood routine test	Day 1 through Day 28
Secondary	Time to first negative in 2019 novel Corona virus RT-PCR test	Oropharyngeal or anal swabs	Up to 28 days
Secondary	All-cause mortality	Date and cause of death (if applicable).	up to 12 weeks
Secondary	Change from baseline in hsCRP	Serum hsCRP	Day 1 through Day 28
Secondary	Change from baseline in cytokines IL-1ß, IL-10, sIL-2R, IL-6, IL-8 and TNF-a	Serum inflammatory cytokines	Day 1 through Day 28
Secondary	Change from baseline in proportion of CD4+CD3/CD8+CD3 T cells	Flow cytometry for peripheral whole blood	Day 1 through Day 28 (if applicable)