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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04306705
Recruitment Status : Recruiting
First Posted : March 13, 2020
Last Update Posted : March 17, 2020
Sponsor:
Collaborators:
Hubei Xinhua Hospital
Wuhan No.1 Hospital
Wuhan central hospital
Information provided by (Responsible Party):
YIKAI YU, 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.

Condition or disease Intervention/treatment
Covid-19 SARS Cytokine Storm Cytokine Release Syndrome Tocilizumab Drug: Tocilizumab Other: Standard of care Procedure: Continuous renal replacement therapy

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.

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Study Type : Observational
Estimated Enrollment : 120 participants
Observational Model: Cohort
Time Perspective: Retrospective
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
Actual Study Start Date : February 20, 2020
Estimated Primary Completion Date : May 30, 2020
Estimated Study Completion Date : June 20, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Tocilizumab

Group/Cohort Intervention/treatment
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.
Drug: Tocilizumab
Administered as an intravenous infusion.
Other Name: Actemra

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.

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

Standard care
Standard of care therapy per local written policies or guidelines.
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.




Primary Outcome Measures :
  1. Proportion of Participants With Normalization of Fever and Oxygen Saturation Through Day 14 [ Time Frame: 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 :
  1. Duration of hospitalization [ Time Frame: Up to 28 days ]
    Measured in days

  2. Proportion of Participants With Normalization of Fever Through Day 14 [ Time Frame: 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.

  3. Change from baseline in white blood cell and differential count [ Time Frame: Day 1 through Day 28 ]
    Blood routine test

  4. Time to first negative in 2019 novel Corona virus RT-PCR test [ Time Frame: Up to 28 days ]
    Oropharyngeal or anal swabs

  5. All-cause mortality [ Time Frame: up to 12 weeks ]
    Date and cause of death (if applicable).

  6. Change from baseline in hsCRP [ Time Frame: Day 1 through Day 28 ]
    Serum hsCRP

  7. Change from baseline in cytokines IL-1β, IL-10, sIL-2R, IL-6, IL-8 and TNF-α [ Time Frame: Day 1 through Day 28 ]
    Serum inflammatory cytokines

  8. Change from baseline in proportion of CD4+CD3/CD8+CD3 T cells [ Time Frame: Day 1 through Day 28 (if applicable) ]
    Flow cytometry for peripheral whole blood



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04306705


Contacts
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Contact: YIKAI YU, M.D +1 (484) 995-5917 yuyikai@163.com
Contact: WEI TU, M.D +86 15671678920

Locations
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China, Hubei
Tongji Hospital Recruiting
Wuhan, Hubei, China, 430030
Contact: AIHUA DU, M.D    +86 2783662886      
Principal Investigator: YIKAI YU, M.D         
Sub-Investigator: SHAOXIAN HU, M.D         
Sub-Investigator: YIHAN YU, M.D         
Sub-Investigator: LINGLI DONG, M.D         
Sub-Investigator: WEI TU, M.D         
Sub-Investigator: RUI XING, M.D         
Sub-Investigator: ZHENG WANG, M.D         
Sub-Investigator: CONG YE, M.D         
Sub-Investigator: FEI YU, M.D         
Sub-Investigator: GUIFEN SHEN, M.D         
Sub-Investigator: YUJIE DAI, M.D         
Sponsors and Collaborators
Tongji Hospital
Hubei Xinhua Hospital
Wuhan No.1 Hospital
Wuhan central hospital
Investigators
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Study Director: SHAOXIAN HU, M.D Tongji Hospital
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Responsible Party: YIKAI YU, Clinical professor, Tongji Hospital
ClinicalTrials.gov Identifier: NCT04306705    
Other Study ID Numbers: WHTJCOVID-19
First Posted: March 13, 2020    Key Record Dates
Last Update Posted: March 17, 2020
Last Verified: March 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Additional relevant MeSH terms:
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Syndrome
Disease
Pathologic Processes