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.
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.
Drug: Infliximab
Either infliximab or infliximab-abda will be used at the discretion of the investigator
Other Name: infliximab-abda
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:
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
Tufts Medical Center
Boston, Massachusetts, United States
Paul Mathew, MD, Principal Investigator
Tufts Medical Center