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

NCT04734678 | Completed DMC FDA Drug

• 1 other identifier: COVID-Infliximab
• Study Type: observational
• Target: 153
• Locations: 1 country
• Sites: 1

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

Keywords

COVID-19; Cytokine Storm; Tocilizumab; Infliximab

Outcome Measures

Primary Outcomes (4)

• Patients' clinical status improvement using six category scale

  The categories were defined as follows: 1) patient discharged, 2) hospitalization not requiring supplemental oxygen, 3) hospitalization requiring supplemental low-flow oxygen, 4) hospitalization requiring high-flow supplemental oxygen, 5) hospitalization requiring invasive mechanical ventilation, 6) death.

  Two weeks

• Time to improvement in oxygenation

  Increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2

  48 hours

• Duration of hospitalization

  Total admission period

  Two weeks

• Mortality rate

  Death during hospitalization

  Two weeks

Secondary Outcomes (7)

• Incidence of non-invasive mechanical ventilation

  Two weeks

• Duration of non-invasive mechanical ventilation

  Two weeks

• Incidence of invasive mechanical ventilation

  Two weeks

• Duration of invasive mechanical ventilation

  Two weeks

• Occurrence of Secondary infections

  Two weeks

Study Arms (2)

Group 1

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

Drug: Tocilizumab

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.

Drug: Tocilizumab; Drug: Infliximab

Interventions

Tocilizumab DRUG

400 mg IV only once

Also known as: Actemra

Group 1; Group 2

Infliximab DRUG

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

Also known as: Remicade

Group 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

All patients received the same background treatment for 5 days, following an Institutional protocol for standard of care: hydroxychloroquine 400 mg daily, lopinavir/ritonavir 400/100 mg twice daily or/and remdisivir 200 mg LD then 100 once daily as a maintenance dose and anti-coagulation prophylaxis with enoxaparin subcutaneously once a day if D-dimmer between 500-1000 or enoxaparin therapeutic subcutaneously twice daily if D-dimmer \>1000.

You may qualify if:

• Age 18-65 years.
• Able to provide informed consent.
• Patients hospitalized with pneumonia proved by chest X-ray or CT scan.
• Confirmed infection with COVID-2019 using RT-PCR or strongly suspected to be infected with pending confirmation studies.
• 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).
• And at least one of the following:
• Respiratory frequency ≥30/min.
• Blood oxygen saturation ≤93% on room air (RA).
• Partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) \<300 \[18\].
• 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.

You may not qualify if:

• Evidence of concomitant bacterial infection.
• Concomitant use of other immunosuppressive biologic drugs.
• Baseline elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels \> 5-fold the upper limit of the normal range.
• Pregnancy.
• Treatment with any TNFα inhibitor in the past 30 days.
• Known hypersensitivity to any TNFα inhibitor, murine proteins, or any component of the formulation.
• Known or suspected active tuberculosis (TB) or a history of incompletely treated or latent TB.
• Serious co-morbidity, including:
• Myocardial infarction (within last month).
• Moderate or severe heart failure (New York Heart Association (NYHA) class III or IV).
• Hepatic patients child Pugh class C.

Sponsors & Collaborators

• Ain Shams University: lead
• Misr International University: collaborator

Study Sites (1)

Teachers Hospital

Cairo, Please Select, 11314, Egypt

Location

Related Publications (1)

• 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.

  PMID: 37081046 DERIVED

MeSH Terms

Conditions

COVID-19; Cytokine Release Syndrome; Coronavirus Infections

Interventions

tocilizumab; Infliximab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Neven Sarhan, PhD

  Misr International University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer at Faculty of Pharmacy

Study Record Dates

• First Submitted: January 31, 2021
• First Posted: February 2, 2021
• Study Start: December 1, 2020
• Primary Completion: June 1, 2021
• Study Completion: August 1, 2021
• Last Updated: July 20, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)