Covid19NCT04734678
Comparison of Tocilizumab Versus Tocilizumab/Infliximab in Patients With COVID-19-associated Cytokine Storm Syndrome
An observational study of Covid19 and Cytokine Storm, run by Ain Shams University at 1 site in Egypt.
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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Covid19, Cytokine Storm, Corona Virus Infection
- What is being tested?
- Tocilizumab and Infliximab
- Type of treatment
- Injection or infusion
- How many people
- 153 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Dec 2020to 1 Aug 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Adult, Older adult
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.
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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
- Being tested
- Tocilizumab, Infliximab
- Keywords
- COVID-19, Cytokine Storm, Tocilizumab, Infliximab
- Medical subject headings
- COVID-19, Cytokine Release Syndrome, Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
Also called Actemra
400 mg IV only once
InfliximabDrug
Also called Remicade
5 mg/kg/day IV for 2 doses 12-24 hours
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Moderate and severe patients who were infected with SARS-CoV-2 and received treatment with tocilizumab in addition to standard management. Receives: 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. Receives: Drug: Tocilizumab; Drug: Infliximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Two weeks
Time to improvement in oxygenation
Increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2
Measured: 48 hours
Duration of hospitalization
Total admission period
Measured: Two weeks
Mortality rate
Death during hospitalization
Measured: Two weeks
Secondary outcomes (7)
Incidence of non-invasive mechanical ventilation
Need for non-invasive mechanical ventilation
Measured: Two weeks
Duration of non-invasive mechanical ventilation
Time required for non-invasive mechanical ventilation
Measured: Two weeks
Incidence of invasive mechanical ventilation
Need for invasive mechanical ventilation
Measured: Two weeks
Duration of invasive mechanical ventilation
Time required for invasive mechanical ventilation
Measured: Two weeks
Occurrence of Secondary infections
Especially Sepsis
Measured: Two weeks
Monitoring of adverse events
Monitoring of adverse events especially elevation of liver enzymes daily
Measured: Two weeks
Occurrence of cardiovascular events
Prevalence of heart failure, tachycardia and hypertension
Measured: Two weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2021
- Study start1 Dec 2020
- Primary completion1 Jun 2021
- Study completion1 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 153 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Collaborators
- Misr International University
- Responsible party
- Principal investigator, Neven Sarhan, Misr International University
- Investigators
- Neven Sarhan, PhD, Principal investigator, Misr International University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04734678
- Sponsor's protocol ID
- COVID-Infliximab
- Status last verified
- Jul 2022
- First submitted
- 31 Jan 2021
- Last updated
- 20 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37081046
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Tocilizumab Versus Tocilizumab/Infliximab in Patients With COVID-19-associated Cytokine Storm Syndrome
- ClinicalTrials.gov ID
- NCT04734678
- Acronym / sponsor ID
- COVID-Infliximab
- Conditions
- Covid19, Cytokine Storm, Corona Virus Infection
- Keywords
- COVID-19, Cytokine Storm, Tocilizumab, Infliximab
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 153 participants (actual)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Collaborators
- Misr International University
- Study start
- 1 Dec 2020 (actual)
- Primary completion
- 1 Jun 2021 (actual)
- Study completion
- 1 Aug 2021 (actual)
- First posted
- 2 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | – | Drug: TocilizumabModerate and severe patients who were infected with SARS-CoV-2 and received treatment with tocilizumab in addition to standard management. |
| Group 2 | – | Drug: Tocilizumab, Drug: InfliximabModerate and severe patients who were infected with SARS-CoV-2 and received treatment with infliximab and tocilizumab in addition to standard management. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (10 listed)
- 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).
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TocilizumabAlso: Actemra400 mg IV only once | Drug | Group 1, Group 2 |
| InfliximabAlso: Remicade5 mg/kg/day IV for 2 doses 12-24 hours | Drug | Group 2 |
Primary outcome
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.
Time to improvement in oxygenation
Time frame: 48 hours
Increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2
Duration of hospitalization
Time frame: Two weeks
Total admission period
Mortality rate
Time frame: Two weeks
Death during hospitalization
7 secondary outcomes
Incidence of non-invasive mechanical ventilation
Time frame: Two weeks
Duration of non-invasive mechanical ventilation
Time frame: Two weeks
Incidence of invasive mechanical ventilation
Time frame: Two weeks
Duration of invasive mechanical ventilation
Time frame: Two weeks
Occurrence of Secondary infections
Time frame: Two weeks
Monitoring of adverse events
Time frame: Two weeks
Occurrence of cardiovascular events
Time frame: Two weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2022.
- Derived from this study: PubMed 37081046Sarhan 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Neven Sarhan, PhD principal investigator
Misr International University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Covid19 and Cytokine Storm, run by Ain Shams University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patients' clinical status improvement using six category scale (time frame: Two weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04734678, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2022.