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

Phase 2

Completed

Conditions: COVID-19

Interventions: Drug: Infliximab

Registration Number: NCT04425538

Lead Sponsor: Tufts Medical Center

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 17

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:
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

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:
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Infliximab	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.

Primary Outcome Measures

Name	Time	Method
Number of p[Atients With Improvement in Oxygenation	28 Days	Number of participants who showed improvement in oxygenation (increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2)
Time to Improvement in Oxygenation	28 Days	Time to improvement in oxygenation (increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2)

Secondary Outcome Measures

Name	Time	Method
Duration of Non-invasive Ventilation or by Non-rebreather Mask or High-flow Nasal Cannula	28 Days	Duration of non-invasive ventilation or by non-rebreather mask or high-flow nasal cannula
Number of Patients Requiring Mechanical Ventilation	28 Days	Number of patients enrolled who required mechanical ventilation
Number of Patients With Fever	28 Days	Number of patients who exhibited fever during the study period
Correlation of Dynamic Changes in IP-10 to Cytokine Profile	3 Days	Correlation of dynamic changes in IP-10 to cytokine profile between day 3 and baseline
Number of Patients Who Developed Secondary Infections	28 Days	Number of patients who developed secondary infections
Number of Patients Requiring Vasopressor Support	28 Days	Number of participants who required vasopressor support
Number of Patients Requiring Supplemental Oxygen Administration by Nasal Cannula	28 Days	Incidence of supplemental oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device
Duration of Mechanical Ventilation	28 Days	duration of use of mechanical ventilation (for patients requiring mechanical ventilation)
Duration of Supplemental Oxygen Administration by Nasal Cannula	28 Days	Duration of supplemental oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device
28-Day Survival Status	28 Days	Number of patients who were confirmed to be alive 28 days from enrollment onto the study.
Number of Patients Requiring Extracorporeal Membrane Oxygenation	28 Days	Number of patients requiring extracorporeal membrane oxygenation
Duration of Hospitalization	28 Days	Duration of hospitalization
Number of Patients Requiring Non-invasive Ventilation or by Non-rebreather Mask or High-flow Nasal Cannula	28 Days	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	Baseline	Assessment of cytokine and inflammatory profile at baseline (TNFα, IL-1b, IL-2, IL-6, ferritin) after therapy