Comparison of Tocilizumab Versus Tocilizumab/Infliximab in Patients With COVID-19-associated Cytokine Storm Syndrome

NCT ID: NCT04734678

Last Updated: 2022-07-20

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 153 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-12-01
• Study Completion Date: 2021-08-01

Brief Summary

Since the end of 2019, Egypt and the whole world have been suffering from the Coronavirus Disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). According to the World Health Organization (WHO), since the emergence of this new pandemic, there have been more than 97 million confirmed cases of COVID-19 patients and two million death globally; around 160 thousand of these cases are in Egypt.

Tocilizumab play role among the unique therapeutic alternatives for the management of cytokine release syndrome (CRS), a life-threatening complication of chimeric antigen receptor (CAR) - T cell therapy. CRS occurs as a result of uncontrolled immune activation with release of pro-inflammatory cytokines and chemokines. Up till now, clinical trial and expertise with tocilizumab in COVID-19 patients has been limited. Despite preliminary encouraging results, recent studies suffered from limitations such as the absence of consistent treatment outline, a short post-treatment follow-up, and the absence of a comparison group.

A recent study discussed the possible beneficial effect of tumor necrosis factor (TNF) inhibitors in severe COVID-19. Specifically, TNF may aggravate lymphopenia through direct killing via TNF/TNFR1 signaling in T cells, and T cell dysfunction reveals an important yet underestimated target for immunomodulatory therapeutic approaches. Accordingly, anti-TNF may be considered as an encouraging therapeutic option in severe COVID-19.

These promising clinical findings encouraged us to use infliximab (IFX), a chimeric monoclonal anti-TNF antibody, as an experimental therapy in patients with moderate and severe COVID-19 in the absence of IBD.

In this study, we compare the outcomes of a large cohort of patients with moderate and severe COVID-19 pneumonia treated with tocilizumab in addition to standard management, with those of concomitantly hospitalized patients who received infliximab and tocilizumab in addition to standard management.

Conditions

Covid19; Cytokine Storm; Corona Virus Infection

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Study Groups

Group 1

Moderate and severe patients who were infected with SARS-CoV-2 and received treatment with tocilizumab in addition to standard management.

Tocilizumab

Intervention Type: DRUG

400 mg IV only once

Group 2

Moderate and severe patients who were infected with SARS-CoV-2 and received treatment with infliximab and tocilizumab in addition to standard management.

Tocilizumab

Intervention Type: DRUG

400 mg IV only once

Infliximab

Intervention Type: DRUG

5 mg/kg/day IV for 2 doses 12-24 hours

Interventions

Tocilizumab

400 mg IV only once

Intervention Type: DRUG

Infliximab

5 mg/kg/day IV for 2 doses 12-24 hours

Intervention Type: DRUG

Other Intervention Names

Actemra; Remicade

Eligibility Criteria

Inclusion Criteria

1. Age 18-65 years.

2. Able to provide informed consent.

3. Patients hospitalized with pneumonia proved by chest X-ray or CT scan.

4. Confirmed infection with COVID-2019 using RT-PCR or strongly suspected to be infected with pending confirmation studies.

5. Hyper-inflammation defined as elevation in either C-reactive protein (CRP, ≥ 100 mg/L, normal values <6 mg/L) or ferritin (≥ 900 ng/mL, normal value <400 ng/mL), in the presence of increased lactate dehydrogenase (LDH, >220 U/L).

6. And at least one of the following:

1. Respiratory frequency ≥30/min.

2. Blood oxygen saturation ≤93% on room air (RA).

3. Partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) <300 [18].

4. Worsening of lung involvement, defined as an increase in number and/or extension of pulmonary areas of consolidation, need for increased FiO2 to maintain stable O2 saturation, or worsening O2 saturation of >3% with stable FiO2.

Exclusion Criteria

1. Evidence of concomitant bacterial infection.

2. Concomitant use of other immunosuppressive biologic drugs.

3. Baseline elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 5-fold the upper limit of the normal range.

4. Pregnancy.

5. Treatment with any TNFα inhibitor in the past 30 days.

6. Known hypersensitivity to any TNFα inhibitor, murine proteins, or any component of the formulation.

7. Known or suspected active tuberculosis (TB) or a history of incompletely treated or latent TB.

8. Serious co-morbidity, including:

1. Myocardial infarction (within last month).

2. Moderate or severe heart failure (New York Heart Association (NYHA) class III or IV).

3. Hepatic patients child Pugh class C.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Misr International University

OTHER

Sponsor Role: collaborator

Ain Shams University

OTHER

Sponsor Role: lead

Responsible Party

Neven Sarhan

Lecturer at Faculty of Pharmacy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Neven Sarhan, PhD

Role: PRINCIPAL_INVESTIGATOR

Misr International University

Locations

Teachers Hospital

Cairo, Please Select, Egypt

Countries

Egypt

References

Sarhan NM, Warda AEA, Ibrahim HSG, Schaalan MF, Fathy SM. Evaluation of infliximab/tocilizumab versus tocilizumab among COVID-19 patients with cytokine storm syndrome. Sci Rep. 2023 Apr 20;13(1):6456. doi: 10.1038/s41598-023-33484-6.

Reference Type: DERIVED

PMID: 37081046 (View on PubMed)

Other Identifiers

COVID-Infliximab

Identifier Type: -

Identifier Source: org_study_id