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

March 16, 2020 updated by: YIKAI YU, Tongji Hospital

A Retrospective Study of Evaluating Safety and Efficacy of Tocilizumab Compared to Continuous Renal Replacement Therapy in Controlling CRS Triggered by COVID-19

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
120

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: YIKAI YU, M.D
  • Phone Number: +1 (484) 995-5917
  • Email: yuyikai@163.com

Study Contact Backup

  • Name: WEI TU, M.D
  • Phone Number: +86 15671678920

Study Locations

  • China
    • Hubei
      • Wuhan, Hubei, China, 430030
        • Recruiting
        • Tongji Hospital
        • Contact:
          • AIHUA DU, M.D
          • Phone Number: +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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
First dose date up to 14 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Duration of hospitalization
Time Frame: Up to 28 days
Measured in days
Up to 28 days
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.
First dose date up to 14 days
Change from baseline in white blood cell and differential count
Time Frame: Day 1 through Day 28
Blood routine test
Day 1 through Day 28
Time to first negative in 2019 novel Corona virus RT-PCR test
Time Frame: Up to 28 days
Oropharyngeal or anal swabs
Up to 28 days
All-cause mortality
Time Frame: up to 12 weeks
Date and cause of death (if applicable).
up to 12 weeks
Change from baseline in hsCRP
Time Frame: Day 1 through Day 28
Serum hsCRP
Day 1 through Day 28
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
Day 1 through Day 28
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
Day 1 through Day 28 (if applicable)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tongji Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Wuhan Central Hospital
Wuhan No.1 Hospital
Hubei Xinhua Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: SHAOXIAN HU, M.D, Tongji Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 20, 2020

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 30, 2020

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 20, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 8, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 12, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 13, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 17, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 16, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • WHTJCOVID-19

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

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