COVID-19Phase 2NCT04425538
A Phase 2 Trial of Infliximab in Coronavirus Disease 2019 (COVID-19).
A Phase 2 study testing Infliximab in people with COVID-19, run by Tufts Medical Center at 1 site in United States.
Trial summary
The investigators hypothesize that early institution of TNFα inhibitor therapy in patients with severe COVID-19 infections will prevent further clinical deterioration and reduce the need for advanced cardiorespiratory support and early mortality. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Infliximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2020to 22 Jan 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older
- Able to provide informed consent
- Hospitalized adult patients with pneumonia evidenced by chest X-ray or CT scan
- Laboratory (RT-PCR) confirmed infection with 2019-nCoV or strongly suspected to be infected with SARS-COV2 with confirmation studies pending
- And at least one of the following:
- Respiratory frequency ≥30/min
Show all 9Show fewer
- Blood oxygen saturation ≤93% on RA
- Partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) <300
- 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
- Treatment with any TNFα inhibitor in the past 30 days
- Known hypersensitivity to any TNFα inhibitor, murine proteins, or any component of the formulation
- Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count (ANC) less than 1000 mm3, hemoglobin <8.0g/L, platelets <50,000 per mm3, or AST or ALT greater than 5 x ULN
- Known active or latent Hepatitis B
- Known or suspected active tuberculosis (TB) or a history of incompletely treated or latent TB.
- Pregnancy
Show all 14Show fewer
- Intubated for >48hours
- Patients with uncontrolled systemic bacterial or fungal infections (Patients with a history of positive bacterial or fungal cultures but on enrollment are on appropriate therapy with negative repeat cultures may be enrolled)
- Serious co-morbidity, including:
- Myocardial infarction (within last month)
- Moderate or severe heart failure (New York Heart Association (NYHA) class III or IV)
- Acute stroke (within last month)
- Uncontrolled malignancy
- Stage 4 severe chronic kidney disease or requiring dialysis (i.e. estimated glomerular filtration rate (eGFR) < 30 ml /min/1.73 m^2) at baseline
Trial locations and contacts
1 site in 1 country.
About this study
The investigators hypothesize that early institution of TNFα inhibitor therapy in patients with severe COVID-19 infections will prevent further clinical deterioration and reduce the need for advanced cardiorespiratory support and early mortality. To address this hypothesis, a prospective, single center, phase 2 trial is proposed to assess the efficacy of infliximab or infliximab-abda in hospitalized adult patients with severe or critical COVID-19. Observations from this study will inform the conduct of prospective randomized controlled studies to follow.
Read the detailed description
The investigators hypothesize that early institution of TNFα inhibitor therapy in patients with severe COVID-19 infections will prevent further clinical deterioration and reduce the need for advanced cardiorespiratory support and early mortality. To address this hypothesis, a prospective, single center, phase 2 trial is proposed to assess the efficacy of infliximab or infliximab-abda in hospitalized adult patients with severe or critical COVID-19. Observations from this study will inform the conduct of prospective randomized controlled studies to follow.
Infliximab and Infliximab-abda are TNFα inhibitors currently FDA-approved for the treatment of autoimmune disorders, including Crohn's disease and rheumatoid arthritis. The risks and adverse reactions are described in the approved prescribing information for infliximab (or infliximab-abda). Infliximab will be used when available. Should infliximab be unavailable in the pharmacy, infliximab-abda, a biosimilar, will be used.
Treatment with infliximab or infliximab-abda 5mg/kg IV should ideally be administered within 6 hours of enrollment, and no more than 24 hours following enrollment. Pre-medication with Tylenol 650 mg once 30 minutes prior to infusion would be recommended. Other pre-medications may be given at the discretion of the treating physician. These include diphenhydramine 50mg by mouth, as well as prednisone 20mg by mouth, both given 30 minutes prior to infusion. Pulse and blood pressure should be monitored every 30 minutes during the infusion, and patients should be monitored for at least 30 minutes following the infusion.
Retreatment with infliximab is permitted at treating physician discretion 7-21 days following primary therapy and based on initial response; the usual treatment schedule is every 2 weeks, this interval is not strictly enforced given the uncertainty of outcomes with primary therapy.
- Conditions
- COVID-19
- Being tested
- Infliximab
- Keywords
- COVID-19
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InfliximabDrug
Also called infliximab-abda
Either infliximab or infliximab-abda will be used at the discretion of the investigator
| Study group | Role | What they receive |
|---|---|---|
| Infliximab | Experimental | All patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. Receives: Drug: Infliximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Improvement in Oxygenation
Time to improvement in oxygenation (increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2)
Measured: 28 Days
Number of p[Atients With Improvement in Oxygenation
Number of participants who showed improvement in oxygenation (increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2)
Measured: 28 Days
Secondary outcomes (14)
28-Day Survival Status
Number of patients who were confirmed to be alive 28 days from enrollment onto the study.
Measured: 28 Days
Duration of Supplemental Oxygen Administration by Nasal Cannula
Duration of supplemental oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device
Measured: 28 Days
Duration of Non-invasive Ventilation or by Non-rebreather Mask or High-flow Nasal Cannula
Duration of non-invasive ventilation or by non-rebreather mask or high-flow nasal cannula
Measured: 28 Days
Number of Patients Requiring Mechanical Ventilation
Number of patients enrolled who required mechanical ventilation
Measured: 28 Days
Number of Patients Requiring Vasopressor Support
Number of participants who required vasopressor support
Measured: 28 Days
Number of Patients Requiring Extracorporeal Membrane Oxygenation
Number of patients requiring extracorporeal membrane oxygenation
Measured: 28 Days
Number of Patients With Fever
Number of patients who exhibited fever during the study period
Measured: 28 Days
Correlation of Dynamic Changes in IP-10 to Cytokine Profile
Correlation of dynamic changes in IP-10 to cytokine profile between day 3 and baseline
Measured: 3 Days
Duration of Hospitalization
Duration of hospitalization
Measured: 28 Days
Number of Patients Who Developed Secondary Infections
Number of patients who developed secondary infections
Measured: 28 Days
Number of Patients Requiring Supplemental Oxygen Administration by Nasal Cannula
Incidence of supplemental oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device
Measured: 28 Days
Duration of Mechanical Ventilation
duration of use of mechanical ventilation (for patients requiring mechanical ventilation)
Measured: 28 Days
Number of Patients Requiring Non-invasive Ventilation or by Non-rebreather Mask or High-flow Nasal Cannula
Number of participants who required non-invasive ventilation or by non-rebreather mask or high-flow nasal cannula
Measured: 28 Days
Assessment of Cytokine and Inflammatory Profile at Baseline
Assessment of cytokine and inflammatory profile at baseline (TNFα, IL-1b, IL-2, IL-6, ferritin) after therapy
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start1 Jun 2020
- Primary completion22 Jan 2021
- Study completion22 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tufts Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Paul Mathew, MD, Principal investigator, Tufts Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04425538
- Sponsor's protocol ID
- STUDY00000564
- Status last verified
- Apr 2022
- First submitted
- 8 Jun 2020
- Last updated
- 20 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hachem H, Godara A, Schroeder C, Fein D, Mann H, Lawlor C, Marshall J, Klein A, Poutsiaka D, Breeze JL, Joshi R, Mathew P. Rapid and sustained decline in CXCL-10 (IP-10) annotates clinical outcomes following TNF-alpha antagonist therapy in hospitalized patients with severe and critical COVID-19 respiratory failure. medRxiv [Preprint]. 2021 Jun 2:2021.05.29.21258010. doi: 10.1101/2021.05.29.21258010.
PubMed 34100026Hachem H, Godara A, Schroeder C, Fein D, Mann H, Lawlor C, Marshall J, Klein A, Poutsiaka D, Breeze JL, Joshi R, Mathew P. Rapid and sustained decline in CXCL-10 (IP-10) annotates clinical outcomes following TNFalpha-antagonist therapy in hospitalized patients with severe and critical COVID-19 respiratory failure. J Clin Transl Sci. 2021 Jun 25;5(1):e146. doi: 10.1017/cts.2021.805. eCollection 2021.
PubMed 34457357
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Trial of Infliximab in Coronavirus Disease 2019 (COVID-19).
- ClinicalTrials.gov ID
- NCT04425538
- Acronym / sponsor ID
- STUDY00000564
- Conditions
- COVID-19
- Keywords
- COVID-19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Tufts Medical CenterUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- 1 Jun 2020 (actual)
- Primary completion
- 22 Jan 2021 (actual)
- Study completion
- 22 Jan 2021 (actual)
- First posted
- 11 Jun 2020 (actual)
- Results
- Posted 3 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators hypothesize that early institution of TNFα inhibitor therapy in patients with severe COVID-19 infections will prevent further clinical deterioration and reduce the need for advanced cardiorespiratory support and early mortality. To address this hypothesis, a prospective, single center, phase 2 trial is proposed to assess the efficacy of infliximab or infliximab-abda in hospitalized adult patients with severe or critical COVID-19. Observations from this study will inform the conduct of prospective randomized controlled studies to follow.
Detailed description
The investigators hypothesize that early institution of TNFα inhibitor therapy in patients with severe COVID-19 infections will prevent further clinical deterioration and reduce the need for advanced cardiorespiratory support and early mortality. To address this hypothesis, a prospective, single center, phase 2 trial is proposed to assess the efficacy of infliximab or infliximab-abda in hospitalized adult patients with severe or critical COVID-19. Observations from this study will inform the conduct of prospective randomized controlled studies to follow.
Infliximab and Infliximab-abda are TNFα inhibitors currently FDA-approved for the treatment of autoimmune disorders, including Crohn's disease and rheumatoid arthritis. The risks and adverse reactions are described in the approved prescribing information for infliximab (or infliximab-abda). Infliximab will be used when available. Should infliximab be unavailable in the pharmacy, infliximab-abda, a biosimilar, will be used.
Treatment with infliximab or infliximab-abda 5mg/kg IV should ideally be administered within 6 hours of enrollment, and no more than 24 hours following enrollment. Pre-medication with Tylenol 650 mg once 30 minutes prior to infusion would be recommended. Other pre-medications may be given at the discretion of the treating physician. These include diphenhydramine 50mg by mouth, as well as prednisone 20mg by mouth, both given 30 minutes prior to infusion. Pulse and blood pressure should be monitored every 30 minutes during the infusion, and patients should be monitored for at least 30 minutes following the infusion.
Retreatment with infliximab is permitted at treating physician discretion 7-21 days following primary therapy and based on initial response; the usual treatment schedule is every 2 weeks, this interval is not strictly enforced given the uncertainty of outcomes with primary therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Infliximab | Experimental | Drug: InfliximabAll patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age 18 years or older
- Able to provide informed consent
- Hospitalized adult patients with pneumonia evidenced by chest X-ray or CT scan
- Laboratory (RT-PCR) confirmed infection with 2019-nCoV or strongly suspected to be infected with SARS-COV2 with confirmation studies pending
- And at least one of the following:
Key exclusion criteria (14 listed)
- Treatment with any TNFα inhibitor in the past 30 days
- Known hypersensitivity to any TNFα inhibitor, murine proteins, or any component of the formulation
- Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count (ANC) less than 1000 mm3, hemoglobin <8.0g/L, platelets <50,000 per mm3, or AST or ALT greater than 5 x ULN
- Known active or latent Hepatitis B
- Known or suspected active tuberculosis (TB) or a history of incompletely treated or latent TB.
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 |
|---|---|---|
| InfliximabAlso: infliximab-abdaEither infliximab or infliximab-abda will be used at the discretion of the investigator | Drug | Infliximab |
Primary outcome
Time to Improvement in Oxygenation
Time frame: 28 Days
Time to improvement in oxygenation (increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2)
Number of p[Atients With Improvement in Oxygenation
Time frame: 28 Days
Number of participants who showed improvement in oxygenation (increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2)
14 secondary outcomes
28-Day Survival Status
Time frame: 28 Days
Duration of Supplemental Oxygen Administration by Nasal Cannula
Time frame: 28 Days
Duration of Non-invasive Ventilation or by Non-rebreather Mask or High-flow Nasal Cannula
Time frame: 28 Days
Number of Patients Requiring Mechanical Ventilation
Time frame: 28 Days
Number of Patients Requiring Vasopressor Support
Time frame: 28 Days
Number of Patients Requiring Extracorporeal Membrane Oxygenation
Time frame: 28 Days
Number of Patients With Fever
Time frame: 28 Days
Correlation of Dynamic Changes in IP-10 to Cytokine Profile
Time frame: 3 Days
Duration of Hospitalization
Time frame: 28 Days
Number of Patients Who Developed Secondary Infections
Time frame: 28 Days
Number of Patients Requiring Supplemental Oxygen Administration by Nasal Cannula
Time frame: 28 Days
Duration of Mechanical Ventilation
Time frame: 28 Days
Number of Patients Requiring Non-invasive Ventilation or by Non-rebreather Mask or High-flow Nasal Cannula
Time frame: 28 Days
Assessment of Cytokine and Inflammatory Profile at Baseline
Time frame: Baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 34100026Hachem H, Godara A, Schroeder C, Fein D, Mann H, Lawlor C, Marshall J, Klein A, Poutsiaka D, Breeze JL, Joshi R, Mathew P. Rapid and sustained decline in CXCL-10 (IP-10) annotates clinical outcomes following TNF-alpha antagonist therapy in hospitalized patients with severe and critical COVID-19 respiratory failure. medRxiv [Preprint]. 2021 Jun 2:2021.05.29.21258010. doi: 10.1101/2021.05.29.21258010.
- Results publication: PubMed 34457357Hachem H, Godara A, Schroeder C, Fein D, Mann H, Lawlor C, Marshall J, Klein A, Poutsiaka D, Breeze JL, Joshi R, Mathew P. Rapid and sustained decline in CXCL-10 (IP-10) annotates clinical outcomes following TNFalpha-antagonist therapy in hospitalized patients with severe and critical COVID-19 respiratory failure. J Clin Transl Sci. 2021 Jun 25;5(1):e146. doi: 10.1017/cts.2021.805. eCollection 2021.
- 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.
Paul Mathew, MD principal investigator
Tufts Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Infliximab in people with COVID-19, run by Tufts Medical Center at 1 site in United States.
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 9 inclusion and 14 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 Apr 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 United States. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Time to Improvement in Oxygenation (time frame: 28 Days). The study lists 2 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 NCT04425538, which also lists 2 linked publications.
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 Apr 2022.