Back to resultsA Phase 2 Trial of Infliximab in Coronavirus Disease 2019 (COVID-19).
Primary Purpose
COVID-19
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Infliximab
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring COVID-19
Eligibility Criteria
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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
- 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
Sites / Locations
- Tufts Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Infliximab
Arm Description
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.
Outcomes
Primary Outcome Measures
Time to Improvement in Oxygenation
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
Number of participants who showed improvement in oxygenation (increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2)
Secondary Outcome Measures
28-Day Survival Status
Number of patients who were confirmed to be alive 28 days from enrollment onto the study.
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
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
Number of Patients Requiring Mechanical Ventilation
Number of patients enrolled who required mechanical ventilation
Number of Patients Requiring Vasopressor Support
Number of participants who required vasopressor support
Number of Patients Requiring Extracorporeal Membrane Oxygenation
Number of patients requiring extracorporeal membrane oxygenation
Number of Patients With Fever
Number of patients who exhibited fever during the study period
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
Duration of Hospitalization
Duration of hospitalization
Number of Patients Who Developed Secondary Infections
Number of patients who developed secondary infections
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
Duration of Mechanical Ventilation
duration of use of mechanical ventilation (for patients requiring mechanical ventilation)
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
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
Full Information
NCT ID
NCT04425538
First Posted
June 8, 2020
Last Updated
April 15, 2022
Sponsor
Tufts Medical Center
Collaborators
National Institutes of Health (NIH)
1. Study Identification
Unique Protocol Identification Number
NCT04425538
Brief Title
A Phase 2 Trial of Infliximab in Coronavirus Disease 2019 (COVID-19).
Official Title
A Phase 2 Trial of Infliximab in Coronavirus Disease 2019 (COVID-19).
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
June 1, 2020 (Actual)
Primary Completion Date
January 22, 2021 (Actual)
Study Completion Date
January 22, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tufts Medical Center
Collaborators
National Institutes of Health (NIH)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
COVID-19
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
17 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Infliximab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Infliximab
Other Intervention Name(s)
infliximab-abda
Intervention Description
Either infliximab or infliximab-abda will be used at the discretion of the investigator
Primary Outcome Measure Information:
Title
Time to Improvement in Oxygenation
Description
Time to improvement in oxygenation (increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2)
Time Frame
28 Days
Title
Number of p[Atients With Improvement in Oxygenation
Description
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 Outcome Measure Information:
Title
28-Day Survival Status
Description
Number of patients who were confirmed to be alive 28 days from enrollment onto the study.
Time Frame
28 Days
Title
Duration of Supplemental Oxygen Administration by Nasal Cannula
Description
Duration of supplemental oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device
Time Frame
28 Days
Title
Duration of Non-invasive Ventilation or by Non-rebreather Mask or High-flow Nasal Cannula
Description
Duration of non-invasive ventilation or by non-rebreather mask or high-flow nasal cannula
Time Frame
28 Days
Title
Number of Patients Requiring Mechanical Ventilation
Description
Number of patients enrolled who required mechanical ventilation
Time Frame
28 Days
Title
Number of Patients Requiring Vasopressor Support
Description
Number of participants who required vasopressor support
Time Frame
28 Days
Title
Number of Patients Requiring Extracorporeal Membrane Oxygenation
Description
Number of patients requiring extracorporeal membrane oxygenation
Time Frame
28 Days
Title
Number of Patients With Fever
Description
Number of patients who exhibited fever during the study period
Time Frame
28 Days
Title
Correlation of Dynamic Changes in IP-10 to Cytokine Profile
Description
Correlation of dynamic changes in IP-10 to cytokine profile between day 3 and baseline
Time Frame
3 Days
Title
Duration of Hospitalization
Description
Duration of hospitalization
Time Frame
28 Days
Title
Number of Patients Who Developed Secondary Infections
Description
Number of patients who developed secondary infections
Time Frame
28 Days
Title
Number of Patients Requiring Supplemental Oxygen Administration by Nasal Cannula
Description
Incidence of supplemental oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device
Time Frame
28 Days
Title
Duration of Mechanical Ventilation
Description
duration of use of mechanical ventilation (for patients requiring mechanical ventilation)
Time Frame
28 Days
Title
Number of Patients Requiring Non-invasive Ventilation or by Non-rebreather Mask or High-flow Nasal Cannula
Description
Number of participants who required non-invasive ventilation or by non-rebreather mask or high-flow nasal cannula
Time Frame
28 Days
Title
Assessment of Cytokine and Inflammatory Profile at Baseline
Description
Assessment of cytokine and inflammatory profile at baseline (TNFα, IL-1b, IL-2, IL-6, ferritin) after therapy
Time Frame
Baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
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
Exclusion Criteria:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Mathew, MD
Organizational Affiliation
Tufts Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34100026
Citation
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. 2021 Jun 2:2021.05.29.21258010. doi: 10.1101/2021.05.29.21258010. Preprint.
Results Reference
result
PubMed Identifier
34457357
Citation
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.
Results Reference
result
Learn more about this trial
A Phase 2 Trial of Infliximab in Coronavirus Disease 2019 (COVID-19).
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