Tocilizumab in Coronavirus-19 Positive Patients

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04423042
• Other study ID #: REB20-0713
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: July 30, 2020
• Est. completion date: June 2021

Study information

• Verified date: July 2020
• Source: University of Calgary
• Contact: Jacinda R Larson, PhD
• Phone: 4039555537
• Email: jacinda.larson[@]albertahealthservices.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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%.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: June 2021
• Est. primary completion date: June 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age = 18 years

2. All genders

3. Hospitalization for suspected or confirmed SARS-CoV2 infection. COVID-19 diagnosis defined as positive on reverse-transcriptase polymerase chain reaction, with provincial laboratory confirmation.

4. Signs of hyperinflammation (cytokine release syndrome) defined by the presence of any of the following:

i. 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),

5. Anti-interleukin treatment indication as per hyperinflammation team

6. Informed consent for participation in the study

Exclusion Criteria:

1. Goal of Care C (palliative care)

2. Known hypersensitivity to TCZ or its components

3. Current systemic immunosuppressive therapy; anti-interleukin 1 or anti-interleukin 6 treatment

4. 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

5. Current or history of bowel perforation or diverticulitis

6. Suspicion of active or latent tuberculosis

7. Pregnant or breastfeeding patient

8. Patients with known prior liver disease

Related Conditions & MeSH terms

• Coronavirus
• Coronavirus Infections
• COVID-19
• Covid19
• Inflammation
• Severe Acute Respiratory Syndrome
• Severe Acute Respiratory Syndrome Coronavirus 2

Intervention

Biological:
• Tocilizumab
Tocilizumab binds to both soluble and membrane-bound interleukin-6 receptors and has been shown to inhibit interleukin 6-mediated signalling.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Calgary

References & Publications (3)

Alzghari SK, Acuña 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. — View Citation

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. — View Citation

Zhang 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause mortality	Mortality status of participants	Assessed at 30 days post treatment
Secondary	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	Assessed at days 3, 8, 15, 30, 60 post treatment

External Links

•   Hoffmann-La Roche Limited. Product Monograph, ACTEMRA® tocilizumab.