Covid19Phase 3NCT04423042
Tocilizumab in Coronavirus-19 Positive Patients
A Phase 3 study testing Tocilizumab in people with Covid19 and COVID-19, run by University of Calgary.
Trial summary
This is a cohort study of COVID-19 patients with hyperinflammation. It aims to determine the impact of adjunctive Tocilizumab (TCZ) to standard of care on the reduction of hyperinflammation-related mortality in COVID-19. Patients with COVID-19 are at high risk of life-threatening hyperinflammation and death. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19, COVID-19, Severe Acute Respiratory Syndrome Coronavirus 2
- What is being tested?
- Tocilizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- 30 Jul 2020to Jun 2021
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- All genders
- Hospitalization for suspected or confirmed SARS-CoV2 infection. COVID-19 diagnosis defined as positive on reverse-transcriptase polymerase chain reaction, with provincial laboratory confirmation.
- Signs of hyperinflammation (cytokine release syndrome) defined by the presence of any of the following:
- Elevated C-reactive protein (≥70 mg/dl and/or rising since last 24h not due to bacterial infection), ii. Ferritin (>700 mcg/L and/or rising since last 24h),
- Anti-interleukin treatment indication as per hyperinflammation team
- Informed consent for participation in the study
Who cannot join
- Goal of Care C (palliative care)
- Known hypersensitivity to TCZ or its components
- Current systemic immunosuppressive therapy; anti-interleukin 1 or anti-interleukin 6 treatment
- Known active bacterial or fungal infections or other clinical conditions that contraindicate TCZ and cannot be treated or resolved according to the physician's judgment
- Current or history of bowel perforation or diverticulitis
- Suspicion of active or latent tuberculosis
- Pregnant or breastfeeding patient
- Patients with known prior liver disease
Trial locations and contacts
No sites are listed yet.
Namneet Sandhu, MPH contact
About this study
Official title: A Nested Interventional Cohort Study to Assess the Efficacy and Safety of Adjunctive Humanized Monoclonal Interleukin-6 Receptor Blocker Tocilizumab (TCZ) Therapy to Standard of Care for the Reduction of Hyperinflammation Related Mortality in SARS-Cov2 Positive Patients
This is a cohort study of COVID-19 patients with hyperinflammation. It aims to determine the impact of adjunctive Tocilizumab (TCZ) to standard of care on the reduction of hyperinflammation-related mortality in COVID-19. Patients with COVID-19 are at high risk of life-threatening hyperinflammation and death. One in three COVID-19 patients admitted to ICU was found to develop life-threatening hyperinflammation. The risk of death when untreated is estimated to be 50-80%.
Read the detailed description
The novel coronavirus, SARS-Cov2/COVID-19, emerged in late 2019 in Wuhan, China. Quickly, SARS-CoV2 spread to all corners of the globe. In March 2020, The World Health Organization (WHO) declared SARS-CoV2/COVID-19 a pandemic. Individuals infected with SARS-CoV2 have a varied clinical presentation, ranging from asymptomatic or mild respiratory symptoms to severe involvement of the lower respiratory tract, with patients requiring mechanical ventilation. A particular point of interest is how the overall severity and clinical outcomes of COVID-19 patients may be associated with the excessive production of pro-inflammatory cytokines, or hyperinflammation, leading to acute respiratory distress syndrome. This state of hyperinflammation may be associated with increased mortality in COVID-19 patients. Tocilizumab, an Interleukin-6 antagonist, may help treat COVID-19 associated hyperinflammation.
This is a nested interventional cohort study of COVID-19 patients with hyperinflammation. It aims to determine the impact of adjunctive Tocilizumab (TCZ) to standard of care on the reduction of hyperinflammation-related mortality in COVID-19. Patients with COVID-19 are at high risk of life-threatening hyperinflammation and death. One in three COVID-19 patients admitted to ICU was found to develop life-threatening hyperinflammation. The risk of death when untreated is estimated to be 50-80%. TCZ treatment may reduce mortality.
Primary objective: To establish that tocilizumab, in addition to standard of care, reduces the 30-day mortality from hyperinflammation in COVID-19 disease significantly compared to no anti-interleukin therapy plus standard of care.
Secondary objectives: To evaluate the addition of tocilizumab therapy to standard of care on a number of secondary outcomes.
- Conditions
- Covid19, COVID-19, Severe Acute Respiratory Syndrome Coronavirus 2, Coronavirus, Inflammation
- Being tested
- Tocilizumab
- Medical subject headings
- COVID-19, Coronavirus Infections, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabBiological
Also called Actemra
Tocilizumab binds to both soluble and membrane-bound interleukin-6 receptors and has been shown to inhibit interleukin 6-mediated signalling.
| Study group | Role | What they receive |
|---|---|---|
| Tocilizumab Arm | Experimental | Tocilizumab 8 mg/kg IV up to a maximum of 800 mg with possible repetition of the same dosage within 28 hours (the optional second dose after 12 hours but before 28 hours following the first dose), based on the clinical judgement of the attending physician in consultation with the COVID-inflammation team. Receives: Biological: Tocilizumab |
| No Intervention Arm | No intervention | No intervention arm patients will be identified from medical records, as being COVID-19 positive patients with hyperinflammation who did not receive any interleukin antagonist treatment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause mortality
Mortality status of participants
Measured: Assessed at 30 days post treatment
Secondary outcomes (1)
Ordinal Scale for evaluating subject clinical status at days 3, 8, 15, 30, 60 post treatment.
Uninfected, ambulatory, hospitalized: mild disease, hospitalized: severe disease, death
Measured: Assessed at days 3, 8, 15, 30, 60 post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2020
- Study start30 Jul 2020 (estimated)
- Primary completionJun 2021 (estimated)
- Study completionJun 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- More trials run by University of CalgaryThe 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Susanne Benseler, MD PhD, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04423042
- Sponsor's protocol ID
- REB20-0713
- Status last verified
- Jul 2020
- First submitted
- 5 Jun 2020
- Last updated
- 22 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Results will be rapidly published.
Publications
Xu X, Han M, Li T, Sun W, Wang D, Fu B, Zhou Y, Zheng X, Yang Y, Li X, Zhang X, Pan A, Wei H. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A. 2020 May 19;117(20):10970-10975. doi: 10.1073/pnas.2005615117. Epub 2020 Apr 29.
PubMed 32350134Alzghari SK, Acuna VS. Supportive Treatment with Tocilizumab for COVID-19: A Systematic Review. J Clin Virol. 2020 Jun;127:104380. doi: 10.1016/j.jcv.2020.104380. Epub 2020 Apr 21. No abstract available.
PubMed 32353761Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents. 2020 May;55(5):105954. doi: 10.1016/j.ijantimicag.2020.105954. Epub 2020 Mar 29.
PubMed 32234467
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Nested Interventional Cohort Study to Assess the Efficacy and Safety of Adjunctive Humanized Monoclonal Interleukin-6 Receptor Blocker Tocilizumab (TCZ) Therapy to Standard of Care for the Reduction of Hyperinflammation Related Mortality in SARS-Cov2 Positive Patients
- ClinicalTrials.gov ID
- NCT04423042
- Acronym / sponsor ID
- REB20-0713
- Conditions
- Covid19, COVID-19, Severe Acute Respiratory Syndrome Coronavirus 2, Coronavirus, Inflammation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Study start
- 30 Jul 2020 (estimated)
- Primary completion
- Jun 2021 (estimated)
- Study completion
- Jun 2021 (estimated)
- First posted
- 9 Jun 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.
This is a cohort study of COVID-19 patients with hyperinflammation. It aims to determine the impact of adjunctive Tocilizumab (TCZ) to standard of care on the reduction of hyperinflammation-related mortality in COVID-19. Patients with COVID-19 are at high risk of life-threatening hyperinflammation and death. One in three COVID-19 patients admitted to ICU was found to develop life-threatening hyperinflammation. The risk of death when untreated is estimated to be 50-80%.
Detailed description
The novel coronavirus, SARS-Cov2/COVID-19, emerged in late 2019 in Wuhan, China. Quickly, SARS-CoV2 spread to all corners of the globe. In March 2020, The World Health Organization (WHO) declared SARS-CoV2/COVID-19 a pandemic. Individuals infected with SARS-CoV2 have a varied clinical presentation, ranging from asymptomatic or mild respiratory symptoms to severe involvement of the lower respiratory tract, with patients requiring mechanical ventilation. A particular point of interest is how the overall severity and clinical outcomes of COVID-19 patients may be associated with the excessive production of pro-inflammatory cytokines, or hyperinflammation, leading to acute respiratory distress syndrome. This state of hyperinflammation may be associated with increased mortality in COVID-19 patients. Tocilizumab, an Interleukin-6 antagonist, may help treat COVID-19 associated hyperinflammation.
This is a nested interventional cohort study of COVID-19 patients with hyperinflammation. It aims to determine the impact of adjunctive Tocilizumab (TCZ) to standard of care on the reduction of hyperinflammation-related mortality in COVID-19. Patients with COVID-19 are at high risk of life-threatening hyperinflammation and death. One in three COVID-19 patients admitted to ICU was found to develop life-threatening hyperinflammation. The risk of death when untreated is estimated to be 50-80%. TCZ treatment may reduce mortality.
Primary objective: To establish that tocilizumab, in addition to standard of care, reduces the 30-day mortality from hyperinflammation in COVID-19 disease significantly compared to no anti-interleukin therapy plus standard of care.
Secondary objectives: To evaluate the addition of tocilizumab therapy to standard of care on a number of secondary outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tocilizumab Arm | Experimental | Biological: TocilizumabTocilizumab 8 mg/kg IV up to a maximum of 800 mg with possible repetition of the same dosage within 28 hours (the optional second dose after 12 hours but before 28 hours following the first dose), based on the clinical judgement of the attending physician in consultation with the COVID-inflammation team. |
| No Intervention Arm | No intervention | –No intervention arm patients will be identified from medical records, as being COVID-19 positive patients with hyperinflammation who did not receive any interleukin antagonist treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥ 18 years
- All genders
- Hospitalization for suspected or confirmed SARS-CoV2 infection. COVID-19 diagnosis defined as positive on reverse-transcriptase polymerase chain reaction, with provincial laboratory confirmation.
- Signs of hyperinflammation (cytokine release syndrome) defined by the presence of any of the following:
- Anti-interleukin treatment indication as per hyperinflammation team
Key exclusion criteria (8 listed)
- Goal of Care C (palliative care)
- Known hypersensitivity to TCZ or its components
- Current systemic immunosuppressive therapy; anti-interleukin 1 or anti-interleukin 6 treatment
- Known active bacterial or fungal infections or other clinical conditions that contraindicate TCZ and cannot be treated or resolved according to the physician's judgment
- Current or history of bowel perforation or diverticulitis
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: ActemraTocilizumab binds to both soluble and membrane-bound interleukin-6 receptors and has been shown to inhibit interleukin 6-mediated signalling. | Biological | Tocilizumab Arm |
Primary outcome
All-cause mortality
Time frame: Assessed at 30 days post treatment
Mortality status of participants
1 secondary outcome
Ordinal Scale for evaluating subject clinical status at days 3, 8, 15, 30, 60 post treatment.
Time frame: Assessed at days 3, 8, 15, 30, 60 post treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2020.
- Background: PubMed 32350134Xu X, Han M, Li T, Sun W, Wang D, Fu B, Zhou Y, Zheng X, Yang Y, Li X, Zhang X, Pan A, Wei H. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A. 2020 May 19;117(20):10970-10975. doi: 10.1073/pnas.2005615117. Epub 2020 Apr 29.
- Background: PubMed 32353761Alzghari SK, Acuna VS. Supportive Treatment with Tocilizumab for COVID-19: A Systematic Review. J Clin Virol. 2020 Jun;127:104380. doi: 10.1016/j.jcv.2020.104380. Epub 2020 Apr 21. No abstract available.
- Background: PubMed 32234467Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents. 2020 May;55(5):105954. doi: 10.1016/j.ijantimicag.2020.105954. Epub 2020 Mar 29.
- Hoffmann-La Roche Limited. Product Monograph, ACTEMRA® tocilizumab.Link provided by the sponsor.
- Individual participant dataSharing planned: No. Results will be rapidly published.
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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.
Namneet Sandhu, MPH contact
Susanne Benseler, MD PhD principal investigator
University of Calgary
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tocilizumab in people with Covid19 and COVID-19, run by University of Calgary.
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 7 inclusion and 8 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 22 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Jacinda R Larson, PhD (4039555537, jacinda.larson@albertahealthservices.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All-cause mortality (time frame: Assessed at 30 days post treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04423042, which also lists 3 linked publications.
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 22 Jul 2020.