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Completed

NCT Number: NCT04734678

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

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.

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Key information

Conditions

Covid19 COVID-19 Corona Virus Infection Coronaviridae Infections Coronavirus Infections Cytokine Release Syndrome Cytokine Storm Infections Inflammation Lung Diseases Nidovirales Infections Pathologic Processes Pathological Conditions, Signs and Symptoms Pneumonia Pneumonia, Viral RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Shock Systemic Inflammatory Response Syndrome Virus Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Teachers Hospital

Cairo, Please Select, 11314, Egypt

Who can participate

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

Tocilizumab

Drug

400 mg IV only once

Other names: Actemra

Infliximab

Drug

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

Other names: Remicade

Primary outcomes

  1. Patients' clinical status improvement using six category scale

    Time frame: Two weeks

    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.

  2. Time to improvement in oxygenation

    Time frame: 48 hours

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

  3. Duration of hospitalization

    Time frame: Two weeks

    Total admission period

  4. Mortality rate

    Time frame: Two weeks

    Death during hospitalization

Secondary outcomes

  1. Incidence of non-invasive mechanical ventilation

    Time frame: Two weeks

    Need for non-invasive mechanical ventilation

  2. Duration of non-invasive mechanical ventilation

    Time frame: Two weeks

    Time required for non-invasive mechanical ventilation

  3. Incidence of invasive mechanical ventilation

    Time frame: Two weeks

    Need for invasive mechanical ventilation

  4. Duration of invasive mechanical ventilation

    Time frame: Two weeks

    Time required for invasive mechanical ventilation

  5. Occurrence of Secondary infections

    Time frame: Two weeks

    Especially Sepsis

  6. Monitoring of adverse events

    Time frame: Two weeks

    Monitoring of adverse events especially elevation of liver enzymes daily

  7. Occurrence of cardiovascular events

    Time frame: Two weeks

    Prevalence of heart failure, tachycardia and hypertension

Sponsors and collaborators

Lead sponsor

Ain Shams University

Other

Collaborators

  • Misr International University

Registry information

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Feb 2, 2021
Registry last updated
Jul 20, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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