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

Covid19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04734678
• Other study ID #: COVID-Infliximab
• Status: Completed
• Start date: December 1, 2020
• Est. completion date: August 1, 2021

Study information

• Verified date: July 2022
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 153
• Est. completion date: August 1, 2021
• Est. primary completion date: June 1, 2021
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 TNFa inhibitor in the past 30 days.

6. Known hypersensitivity to any TNFa 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.

Related Conditions & MeSH terms

• Corona Virus Infection
• Coronavirus Infections
• COVID-19
• Covid19
• Cytokine Release Syndrome
• Cytokine Storm

Intervention

Drug:
• Tocilizumab
400 mg IV only once
• Infliximab
5 mg/kg/day IV for 2 doses 12-24 hours

Locations

Country	Name	City	State
Egypt	Teachers Hospital	Cairo	Please Select

Sponsors (2)

Lead Sponsor	Collaborator
Ain Shams University	Misr International University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Time to improvement in oxygenation	Increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2	48 hours
Primary	Duration of hospitalization	Total admission period	Two weeks
Primary	Mortality rate	Death during hospitalization	Two weeks
Secondary	Incidence of non-invasive mechanical ventilation	Need for non-invasive mechanical ventilation	Two weeks
Secondary	Duration of non-invasive mechanical ventilation	Time required for non-invasive mechanical ventilation	Two weeks
Secondary	Incidence of invasive mechanical ventilation	Need for invasive mechanical ventilation	Two weeks
Secondary	Duration of invasive mechanical ventilation	Time required for invasive mechanical ventilation	Two weeks
Secondary	Occurrence of Secondary infections	Especially Sepsis	Two weeks
Secondary	Monitoring of adverse events	Monitoring of adverse events especially elevation of liver enzymes daily	Two weeks
Secondary	Occurrence of cardiovascular events	Prevalence of heart failure, tachycardia and hypertension	Two weeks