Covid-19TACOSNCT04306705
Tocilizumab vs CRRT in Management of Cytokine Release Syndrome (CRS) in COVID-19
An observational study of Covid-19 and SARS, run by Tongji Hospital at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Covid-19, SARS, Cytokine Storm
- What is being tested?
- Tocilizumab and Continuous renal replacement therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 120 participants
- Where
- 1 siteChina
- Study dates
- 20 Feb 2020to 20 Jun 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Agrees to the collection of oropharyngeal or anal swabs and venous blood per protocol.
- Male or non-pregnant female adult ≥18 years of age at time of enrollment.
- 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.
- Illness of any duration, and at least one of the following:
- Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR
- Clinical assessment (evidence of rales/crackles on physical examination) AND SpO2 ≤93% on room air, OR
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- Requiring mechanical ventilation and/or supplemental oxygen, OR
- Sustained fever in the past 24 hours and unresponsive to NSAID or steroid
- Serum IL-6 ≥3 times the upper limit of normal
Who cannot join
- Alanine transaminase/aspartate transaminase (ALT/AST) > 5 times the upper limit of normal.
- Stage 4 severe chronic kidney disease or requiring dialysis (i.e. estimated glomerular filtration rate (eGFR) < 30 ml /min/1.73 m^2)
- Hemoglobin<80 g/L
- Leukocytes<2.0×10^9
- Platelets<50×10^9
- Pregnancy or breast feeding.
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- Anticipated transfer to another hospital which is not a study site within 72 hours.
- Expected life span does not exceed 7 days.
- Allergy to any study medication.
Trial locations and contacts
1 site in 1 country.
WEI TU, M.D contact
China1 site, 1 recruiting
- Recruiting
Tongji Hospital
Wuhan, Hubei, 430030
AIHUA DU, M.D, +86 2783662886
YIKAI YU, M.D
About this study
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
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.
Read the 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.
- Conditions
- Covid-19, SARS, Cytokine Storm, Cytokine Release Syndrome, Tocilizumab
- Being tested
- Tocilizumab, Standard of care, Continuous renal replacement therapy
- Medical subject headings
- COVID-19, Cytokine Release Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
Also called Actemra
Administered as an intravenous infusion.
Standard of careOther
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 therapyProcedure or surgery
Catheter insertion site is femoral vein.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Tocilizumab; Other: Standard of care | |
| Continuous Renal Replacement Therapy | Femoral vein catheterization was performed to complete continuous renal replacement therapy for consecutive 3 times or more. Receives: Other: Standard of care; Procedure: Continuous renal replacement therapy | |
| Standard care | Standard of care therapy per local written policies or guidelines. Receives: Other: Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: First dose date up to 14 days
Secondary outcomes (8)
Duration of hospitalization
Measured in days
Measured: Up to 28 days
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.
Measured: First dose date up to 14 days
Change from baseline in white blood cell and differential count
Blood routine test
Measured: Day 1 through Day 28
Time to first negative in 2019 novel Corona virus RT-PCR test
Oropharyngeal or anal swabs
Measured: Up to 28 days
All-cause mortality
Date and cause of death (if applicable).
Measured: up to 12 weeks
Change from baseline in hsCRP
Serum hsCRP
Measured: Day 1 through Day 28
Change from baseline in cytokines IL-1β, IL-10, sIL-2R, IL-6, IL-8 and TNF-α
Serum inflammatory cytokines
Measured: Day 1 through Day 28
Change from baseline in proportion of CD4+CD3/CD8+CD3 T cells
Flow cytometry for peripheral whole blood
Measured: Day 1 through Day 28 (if applicable)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2020
- Study start20 Feb 2020
- Primary completion30 May 2020 (estimated)
- Study completion20 Jun 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid-19Studies of the same condition, open and under way.
- More trials run by Tongji HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tongji Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Hubei Xinhua Hospital, Wuhan No.1 Hospital, Wuhan Central Hospital
- Responsible party
- Principal investigator, YIKAI YU, Tongji Hospital
- Investigators
- SHAOXIAN HU, M.D, Study director, Tongji Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04306705
- Sponsor's protocol ID
- WHTJCOVID-19
- Acronym
- TACOS
- Status last verified
- Mar 2020
- First submitted
- 8 Mar 2020
- Last updated
- 17 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04306705
- Acronym / sponsor ID
- TACOS / WHTJCOVID-19
- Conditions
- Covid-19, SARS, Cytokine Storm, Cytokine Release Syndrome, Tocilizumab
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Tongji HospitalUniversity, hospital or other
- Collaborators
- Hubei Xinhua Hospital, Wuhan No.1 Hospital, Wuhan Central Hospital
- Study start
- 20 Feb 2020 (actual)
- Primary completion
- 30 May 2020 (estimated)
- Study completion
- 20 Jun 2020 (estimated)
- First posted
- 13 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Tocilizumab | – | Drug: Tocilizumab, Other: Standard of careSubjects 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. |
| Continuous Renal Replacement Therapy | – | Other: Standard of care, Procedure: Continuous renal replacement therapyFemoral vein catheterization was performed to complete continuous renal replacement therapy for consecutive 3 times or more. |
| Standard care | – | Other: Standard of careStandard of care therapy per local written policies or guidelines. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (9 listed)
- Agrees to the collection of oropharyngeal or anal swabs and venous blood per protocol.
- Male or non-pregnant female adult ≥18 years of age at time of enrollment.
- 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.
- Illness of any duration, and at least one of the following:
- Serum IL-6 ≥3 times the upper limit of normal
Key exclusion criteria (9 listed)
- Alanine transaminase/aspartate transaminase (ALT/AST) > 5 times the upper limit of normal.
- Stage 4 severe chronic kidney disease or requiring dialysis (i.e. estimated glomerular filtration rate (eGFR) < 30 ml /min/1.73 m^2)
- Hemoglobin<80 g/L
- Leukocytes<2.0×10^9
- Platelets<50×10^9
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TocilizumabAlso: ActemraAdministered as an intravenous infusion. | Drug | Tocilizumab |
| Standard of careStandard 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. | Other | Continuous Renal Replacement Therapy, Standard care, Tocilizumab |
| Continuous renal replacement therapyCatheter insertion site is femoral vein. | Procedure or surgery | Continuous Renal Replacement Therapy |
Primary outcome
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.
8 secondary outcomes
Duration of hospitalization
Time frame: Up to 28 days
Proportion of Participants With Normalization of Fever Through Day 14
Time frame: First dose date up to 14 days
Change from baseline in white blood cell and differential count
Time frame: Day 1 through Day 28
Time to first negative in 2019 novel Corona virus RT-PCR test
Time frame: Up to 28 days
All-cause mortality
Time frame: up to 12 weeks
Change from baseline in hsCRP
Time frame: 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
Change from baseline in proportion of CD4+CD3/CD8+CD3 T cells
Time frame: Day 1 through Day 28 (if applicable)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
WEI TU, M.D contact
SHAOXIAN HU, M.D study director
Tongji Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Covid-19 and SARS, run by Tongji Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact YIKAI YU, M.D (+1 (484) 995-5917, yuyikai@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants With Normalization of Fever and Oxygen Saturation Through Day 14 (time frame: First dose date up to 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2020.