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CompletedNCT04425538Updated Apr 20, 2022Results posted

A Phase 2 Trial of Infliximab in Coronavirus Disease 2019 (COVID-19).

A Phase 2 interventional study of Infliximab in COVID-19, sponsored by Tufts Medical Center. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-04-20.

Sponsored by Tufts Medical Center · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
17
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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. 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.

02

Conditions studied

  • COVID-19

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Keywords

  • COVID-19
03

In context

COVID-19

7,638 studies on the registry are indexed under COVID-19; 488 are open to participants now.

This study's enrollment of 17 is below the median of 100 across 4,098 interventional studies indexed under COVID-19.

Browse COVID-19 studies →

Lead sponsor

Tufts Medical Center is the lead sponsor of 194 studies on the registry; 28 are open to participants now.

Of its 30 completed or terminated interventional studies of FDA-regulated products, 16 (53%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Age 18 years or older
  2. Able to provide informed consent
  3. Hospitalized adult patients with pneumonia evidenced by chest X-ray or CT scan
  4. Laboratory (RT-PCR) confirmed infection with 2019-nCoV or strongly suspected to be infected with SARS-COV2 with confirmation studies pending

  5. And at least one of the following:

    1. Respiratory frequency ≥30/min
    2. Blood oxygen saturation ≤93% on RA
    3. Partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) \<300
    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

Exclusion Criteria:

  1. Treatment with any TNFα inhibitor in the past 30 days
  2. Known hypersensitivity to any TNFα inhibitor, murine proteins, or any component of the formulation
  3. 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
  4. Known active or latent Hepatitis B
  5. Known or suspected active tuberculosis (TB) or a history of incompletely treated or latent TB.
  6. Pregnancy
  7. Intubated for >48hours
  8. 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)

  9. 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. Acute stroke (within last month)
    4. Uncontrolled malignancy
    5. 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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
17 participants (actual)

Study arms

  • Experimental
    Infliximab

    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.

    Drug: Infliximab

Interventions

  • DrugInfliximab

    Either infliximab or infliximab-abda will be used at the discretion of the investigator

    Also known as: infliximab-abda

06

What researchers measure

Primary outcomes

  1. Time to Improvement in Oxygenation

    Time to improvement in oxygenation (increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2)

    Time frame: 28 Days

  2. 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)

    Time frame: 28 Days

Secondary outcomes

  1. 28-Day Survival Status

    Number of patients who were confirmed to be alive 28 days from enrollment onto the study.

    Time frame: 28 Days

  2. 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

    Time frame: 28 Days

  3. 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

    Time frame: 28 Days

  4. Number of Patients Requiring Mechanical Ventilation

    Number of patients enrolled who required mechanical ventilation

    Time frame: 28 Days

  5. Number of Patients Requiring Vasopressor Support

    Number of participants who required vasopressor support

    Time frame: 28 Days

  6. Number of Patients Requiring Extracorporeal Membrane Oxygenation

    Number of patients requiring extracorporeal membrane oxygenation

    Time frame: 28 Days

  7. Number of Patients With Fever

    Number of patients who exhibited fever during the study period

    Time frame: 28 Days

  8. 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

    Time frame: 3 Days

  9. Duration of Hospitalization

    Duration of hospitalization

    Time frame: 28 Days

  10. Number of Patients Who Developed Secondary Infections

    Number of patients who developed secondary infections

    Time frame: 28 Days

  11. 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

    Time frame: 28 Days

  12. Duration of Mechanical Ventilation

    duration of use of mechanical ventilation (for patients requiring mechanical ventilation)

    Time frame: 28 Days

  13. 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

    Time frame: 28 Days

  14. 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

    Time frame: Baseline

07

Results

Posted Dec 3, 2021

Participant flow

Participant flow — Overall Study
MilestoneInfliximab
Started17
Completed17
Not completed0

Outcome measures

PrimaryTime to Improvement in Oxygenation

Time to improvement in oxygenation (increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2)

Time frame:
28 Days
Reported as:
Median · Days
Time to Improvement in Oxygenation
DaysInfliximab
Time to Improvement in Oxygenation4 (1 to 12)
PrimaryNumber 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)

Time frame:
28 Days
Reported as:
Count of participants · Participants
Number of p[Atients With Improvement in Oxygenation
ParticipantsInfliximab
Number of p[Atients With Improvement in Oxygenation15
Secondary28-Day Survival Status

Number of patients who were confirmed to be alive 28 days from enrollment onto the study.

Time frame:
28 Days
Reported as:
Count of participants · Participants
28-Day Survival Status
ParticipantsInfliximab
28-Day Survival Status15
SecondaryDuration of Supplemental Oxygen Administration by Nasal Cannula

Duration of supplemental oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device

Time frame:
28 Days
Reported as:
Median · Days
Duration of Supplemental Oxygen Administration by Nasal Cannula
DaysInfliximab
Duration of Supplemental Oxygen Administration by Nasal Cannula3 (1 to 4)
SecondaryDuration 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

Time frame:
28 Days
Reported as:
Median · Days
Duration of Non-invasive Ventilation or by Non-rebreather Mask or High-flow Nasal Cannula
DaysInfliximab
Duration of Non-invasive Ventilation or by Non-rebreather Mask or High-flow Nasal Cannula2.5 (2 to 6)
SecondaryNumber of Patients Requiring Mechanical Ventilation

Number of patients enrolled who required mechanical ventilation

Time frame:
28 Days
Reported as:
Count of participants · Participants
Number of Patients Requiring Mechanical Ventilation
ParticipantsInfliximab
Number of Patients Requiring Mechanical Ventilation7
SecondaryNumber of Patients Requiring Vasopressor Support

Number of participants who required vasopressor support

Time frame:
28 Days
Reported as:
Count of participants · Participants
Number of Patients Requiring Vasopressor Support
ParticipantsInfliximab
Number of Patients Requiring Vasopressor Support3
SecondaryNumber of Patients Requiring Extracorporeal Membrane Oxygenation

Number of patients requiring extracorporeal membrane oxygenation

Time frame:
28 Days
Reported as:
Count of participants · Participants
Number of Patients Requiring Extracorporeal Membrane Oxygenation
ParticipantsInfliximab
Number of Patients Requiring Extracorporeal Membrane Oxygenation1
SecondaryNumber of Patients With Fever

Number of patients who exhibited fever during the study period

Time frame:
28 Days
Reported as:
Count of participants · Participants
Number of Patients With Fever
ParticipantsInfliximab
Number of Patients With Fever12
SecondaryCorrelation of Dynamic Changes in IP-10 to Cytokine Profile

Correlation of dynamic changes in IP-10 to cytokine profile between day 3 and baseline

Time frame:
3 Days
Reported as:
Number · Correlation coefficient
Correlation of Dynamic Changes in IP-10 to Cytokine Profile
Correlation coefficientInfliximab
CXCL90.652
IL-150.605
FLT-3L0.601
IL-12p400.585
IL-3.571
M-CSF0.564
MDC0.528
IFN-A20.509
IL-5.501
IL-18.484
SecondaryDuration of Hospitalization

Duration of hospitalization

Time frame:
28 Days
Reported as:
Median · days
Duration of Hospitalization
daysInfliximab
Duration of Hospitalization8 (1 to 28)
SecondaryNumber of Patients Who Developed Secondary Infections

Number of patients who developed secondary infections

Time frame:
28 Days
Reported as:
Count of participants · Participants
Number of Patients Who Developed Secondary Infections
ParticipantsInfliximab
Number of Patients Who Developed Secondary Infections7
SecondaryNumber 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

Time frame:
28 Days
Reported as:
Count of participants · Participants
Number of Patients Requiring Supplemental Oxygen Administration by Nasal Cannula
ParticipantsInfliximab
Number of Patients Requiring Supplemental Oxygen Administration by Nasal Cannula14
SecondaryDuration of Mechanical Ventilation

duration of use of mechanical ventilation (for patients requiring mechanical ventilation)

Time frame:
28 Days
Reported as:
Median · days
Duration of Mechanical Ventilation
daysInfliximab
Duration of Mechanical Ventilation10 (5 to 28)
SecondaryNumber 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

Time frame:
28 Days
Reported as:
Count of participants · Participants
Number of Patients Requiring Non-invasive Ventilation or by Non-rebreather Mask or High-flow Nasal Cannula
ParticipantsInfliximab
Number of Patients Requiring Non-invasive Ventilation or by Non-rebreather Mask or High-flow Nasal Cannula8
SecondaryAssessment 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

Time frame:
Baseline
Reported as:
Mean · ng/mL
Assessment of Cytokine and Inflammatory Profile at Baseline
ng/mLInfliximab
TNFα109.2 ± 53.4
IL-1β42.3 ± 97.8
IL-21.46 ± 2.21
IL-669.2 ± 130.85
Ferritin1972.12 ± 1517.56

Adverse events

Collected over Adverse events and serious adverse events were collected for each patient beginning at the time of first infliximab dose through 28 days following the last dose of infliximab. Study-wide, adverse event collection was conducted for approximately 8 months.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Infliximab2/17 (11.8%)2/17 (11.8%)16/17 (94.1%)
Most frequent serious events
Most frequent serious events
EventInfliximab
Cardiac ArrestCardiac disorders1/17
Covid-Associated Pulmonary AspergillosisInfections and infestations1/17
Most frequent other events
Most frequent other events
EventInfliximab
AST ElevationInvestigations9/17
ALT ElevationInvestigations8/17
Lung InfectionInfections and infestations8/17
Acute Kidney InjuryRenal and urinary disorders3/17
Acute Infusion ReactionGeneral disorders2/17
Herpes Simplex ReactivationInfections and infestations2/17
HyperglycemiaInvestigations1/17
Atrial FibrillationCardiac disorders1/17
Intermittent Sinus BradycardiaCardiac disorders1/17

Baseline characteristics

Age, Customized
Age, Customized(Participants)Infliximab
18-40 years1
41-60 years7
>60 years9
Sex: Female, Male
Sex: Female, Male(Participants)Infliximab
Female4
Male13
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Infliximab
Caucasian4
Black/African American2
Chinese3
Other Asian2
Hispanic/Latino4
Other1
Unknown1
Region of Enrollment
Region of Enrollment(participants)Infliximab
United States17
08

Study locations

1 site
  • Tufts Medical Center
    Boston, Massachusetts 02111, United States
09

References and documents

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 34100026 ↗
  • 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 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 documents

  • Protocol and statistical analysis plan · Jun 22, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 20, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04425538
Lead sponsor
Tufts Medical Center
Collaborators
National Institutes of Health (NIH)
Responsible party
Sponsor
First posted
Jun 11, 2020
Start date
Jun 1, 2020
Primary completion
Jan 22, 2021
Completion
Jan 22, 2021
Results posted
Dec 3, 2021
Last update
Apr 20, 2022

Study contacts

Paul Mathew, MD
principal investigator · Tufts Medical Center

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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