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Infliximab in the Treatment of Patients With Severe COVID-19 Disease (INFLIXCOVID)

Primary Purpose

COVID-19

Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Infliximab
Standard of Care
Sponsored by
Jena University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age ≥ 18 years
  • Infection with SARS-CoV-2 (virus detection by means of a PCR test not older than 72 hours)
  • Bipulmonary infiltrates (detection by means of X-rays or computed tomography)
  • COVID inflammation score ≥ 10
  • Ferritin concentration (serum or plasma) ≥ 500 ng / ml
  • Arterial oxygen saturation ≤ 93% when breathing room air
  • written informed consent from the patient
  • Potentially childbearing women: negative pregnancy test

Exclusion Criteria (in medical history):

Contraindications study medication:

  • Hypersensitivity to the active substance infliximab (or any of the other ingredients of the medicine) or to other murine proteins
  • active or latent tuberculosis
  • acute or chronic hepatitis B
  • severe infections such as invasive fungal infections, bacterial sepsis, or abscesses
  • opportunistic infections (e.g. pneumocystosis, listeriosis)
  • moderate or severe heart failure (NYHA class III / IV)
  • Immunosuppression (e.g. organ transplantation, AIDS, leukopenia)
  • Malignancies or lymphoproliferative diseases or chemotherapy within the last 4 weeks
  • Multiple sclerosis or peripheral demyelinating diseases, including the Guillain-Barré syndrome
  • Treatment with other biologics for therapy for approved indications of infliximab (e.g. for rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, psoriasis)

Further exclusion criteria:

  • Autoimmune disease with biologics therapy
  • Current treatment with TNF antibodies, convalescent plasma, bamlanivimab, or other experimental treatments for COVID-19
  • High-flow oxygen therapy, non-invasive / invasive ventilation (WHO-COVID-19 PROGRESSION Scale > 5)
  • pre-existing long-term ventilation or home oxygen therapy
  • Child-Pugh C liver cirrhosis
  • Pregnancy or breastfeeding
  • Patients with a life expectancy < 90 days due to other medical conditions
  • Limitation or discontinuation of therapy (e.g. refusal of artificial ventilation)
  • Participation in another interventional study
  • Previous participation in this study
  • Interdependence between the patient and the coordinating investigator or other members of the study team

Sites / Locations

  • Universitätsklinikum Knappschaftskrankenhaus Bochum
  • Klinikum Fulda
  • Universitätsklinikum Hamburg-Eppendorf
  • Jena University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Infliximab + Standard of Care

Standard of Care

Arm Description

Outcomes

Primary Outcome Measures

28-day mortality
differences in mortality-rates between both study arms (Infliximab + Standard of Care vs. Standard of Care) 28 days after randomisation

Secondary Outcome Measures

safety of Infliximab administration
frequencies of adverse events (AEs) and serious adverse events (SAEs)
assessment of the effect of infliximab on an excessive immune response in patients with COVID-19: Interleukin 6
change in the interleukin-6 (IL-6) concentration in the blood from randomization to day 7 and day 14 after randomization
assessment of the effect of infliximab on an excessive immune response in patients with COVID-19: ferritin
change in the ferritin concentration in the blood from randomization to day 7 and day 14 after randomization
assessment of the effect of infliximab on an excessive immune response in patients with COVID-19: lymphocyte count
change in the lymphocyte count from randomization to day 7 and day 14 after randomization
assessment of the severity and frequency of organ failure: ventilation-free days
ventilation-free days until 28 days after randomization
assessment of the severity and frequency of organ failure: renal replacement therapy-free days
renal replacement therapy-free days until 28 days after randomization
assessment of the severity and frequency of organ failure: vasopressor-free days
vasopressor-free days until 28 days after randomization
occurence of Acute Respiratory Distress Syndrome (ARDS)
rate of occurrence of ARDS until 28 days after randomization
WHO-COVID-19-Progression Scale
WHO-COVID-19-Progression Scale on day 7, 14 and 28 after randomization
rate of admission to the intensive care unit
rate of admission to the intensive care unit after randomization up to day 28
length of stay: hospital
length of hospital stay up to day 28 after randomization
length of stay: intensive care unit
length of intensive care unit stay up to day 28 after randomization
mortality
mortality rates 14 and 90 days after randomization
health related quality of life: visual analogue scale
EQ5D-3L: visual analog scale value 90 days after randomization
health related quality of life: index
EQ5D-3L: index value 90 days after randomization
incidence of cardiomyopathy
incidence of cardiomyopathy 3 and/or 7 days after randomization

Full Information

First Posted
June 10, 2021
Last Updated
July 11, 2023
Sponsor
Jena University Hospital
Collaborators
German Federal Ministry of Education and Research, Celltrion
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1. Study Identification

Unique Protocol Identification Number
NCT04922827
Brief Title
Infliximab in the Treatment of Patients With Severe COVID-19 Disease
Acronym
INFLIXCOVID
Official Title
A Randomized, Controlled, Multicenter, Open Label Phase II Clinical Study to Evaluate Infliximab in the Treatment of Patients With Severe COVID-19 Disease
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
June 18, 2021 (Actual)
Primary Completion Date
March 31, 2023 (Actual)
Study Completion Date
July 1, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jena University Hospital
Collaborators
German Federal Ministry of Education and Research, Celltrion

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In this trial, patients that are severely affected by the disease COVID-19 will either receive infliximab, an anti-inflammatory drug, or standard therapy. Infliximab is a drug that inhibits inflammation by blocking a molecule called TNFα. The patients receive the drug via an infusion into a vein. The primary goal of this trial is to see whether the drug infliximab affects how many people died from COVID-19 after 28 days by comparing patients receiving the drug in addition to standard therapy with patients only receiving standard therapy. Furthermore, this trial will look at whether the drug is safe to use in these patients, whether it has an effect on the inflammation and whether it can affect how ill patients are after surviving the disease. The trial is conducted in more than one hospital. As COVID-19 is responsible for a global pandemic, positive results of this trial could affect patients, healthcare and economic systems worldwide.
Detailed Description
The long-term goal of this research project is to develop a new pharmacological treatment strategy for patients with COVID-19. Its primary aim is the assessment of efficacy and safety of the TNFα antibody infliximab in the treatment of patients with severe COVID-19 in a phase-2 trial. Infliximab is expected to attenuate the inflammatory reaction in patients and thereby positively influence the course of the disease. The primary endpoint is the difference in 28-day-mortality of patients with severe COVID-19 receiving one dose of 5mg per kg body weight infliximab intravenously in addition to the standard of care (intervention group) compared with patients receiving standard of care (control group). Secondary aims of this trial include the assessment of the safety of the TNFα antibody infliximab in the treatment of patients with severe COVID-19, of its effect on an excessive immune response and of its effect on the morbidity and prognosis as well as the characterization of the analytical cohorts. The multi-centre design facilitates the transferability of study results to hospitals of similar healthcare level. Should infliximab prove to be superior to standard therapy, this could be reflected in a reduced disease severity and mortality. The results of this study could influence the therapy of patients with COVID-19 worldwide and affect the course of the disease worldwide, as infliximab is approved by several international drug agencies and globally available. Due to the high incidence of COVID-19 worldwide and the immense effects of the pandemic on societies, health care and economic systems, any progress in the treatment of this new disease would constitute a great success. This would not only impact individual patients but also have positive economic effects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Infliximab + Standard of Care
Arm Type
Experimental
Arm Title
Standard of Care
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Infliximab
Intervention Description
single intravenous administration of 5 milligrams/kilogram
Intervention Type
Other
Intervention Name(s)
Standard of Care
Intervention Description
Standard of Care
Primary Outcome Measure Information:
Title
28-day mortality
Description
differences in mortality-rates between both study arms (Infliximab + Standard of Care vs. Standard of Care) 28 days after randomisation
Time Frame
28 days after randomization
Secondary Outcome Measure Information:
Title
safety of Infliximab administration
Description
frequencies of adverse events (AEs) and serious adverse events (SAEs)
Time Frame
up to 90 days after randomization
Title
assessment of the effect of infliximab on an excessive immune response in patients with COVID-19: Interleukin 6
Description
change in the interleukin-6 (IL-6) concentration in the blood from randomization to day 7 and day 14 after randomization
Time Frame
day 7 and day 14 after randomization
Title
assessment of the effect of infliximab on an excessive immune response in patients with COVID-19: ferritin
Description
change in the ferritin concentration in the blood from randomization to day 7 and day 14 after randomization
Time Frame
day 7 and day 14 after randomization
Title
assessment of the effect of infliximab on an excessive immune response in patients with COVID-19: lymphocyte count
Description
change in the lymphocyte count from randomization to day 7 and day 14 after randomization
Time Frame
day 7 and day 14 after randomization
Title
assessment of the severity and frequency of organ failure: ventilation-free days
Description
ventilation-free days until 28 days after randomization
Time Frame
day 28 after randomization
Title
assessment of the severity and frequency of organ failure: renal replacement therapy-free days
Description
renal replacement therapy-free days until 28 days after randomization
Time Frame
day 28 after randomization
Title
assessment of the severity and frequency of organ failure: vasopressor-free days
Description
vasopressor-free days until 28 days after randomization
Time Frame
day 28 after randomization
Title
occurence of Acute Respiratory Distress Syndrome (ARDS)
Description
rate of occurrence of ARDS until 28 days after randomization
Time Frame
day 28 after randomization
Title
WHO-COVID-19-Progression Scale
Description
WHO-COVID-19-Progression Scale on day 7, 14 and 28 after randomization
Time Frame
day 7, 14 and 28 after randomization
Title
rate of admission to the intensive care unit
Description
rate of admission to the intensive care unit after randomization up to day 28
Time Frame
day 28 after randomization
Title
length of stay: hospital
Description
length of hospital stay up to day 28 after randomization
Time Frame
day 28 after randomization
Title
length of stay: intensive care unit
Description
length of intensive care unit stay up to day 28 after randomization
Time Frame
day 28 after randomization
Title
mortality
Description
mortality rates 14 and 90 days after randomization
Time Frame
day 14 and 90 after randomization
Title
health related quality of life: visual analogue scale
Description
EQ5D-3L: visual analog scale value 90 days after randomization
Time Frame
day 90 after randomization
Title
health related quality of life: index
Description
EQ5D-3L: index value 90 days after randomization
Time Frame
day 90 after randomization
Title
incidence of cardiomyopathy
Description
incidence of cardiomyopathy 3 and/or 7 days after randomization
Time Frame
day 3 and 7 after randomization
Other Pre-specified Outcome Measures:
Title
collection and storage of blood and urine sample
Description
collection and storage of blood and urine sample for the investigation of translational research questions by analysing biomarkers of organ, metabolic and immunological function and regulation
Time Frame
day 3, 7 and 14 after randomization
Title
comparison with other cohorts
Description
comparison of the course of disease of patients with severe COVID-19 and previously generated datasets from patients with sepsis and health subjects
Time Frame
up to day 90 after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years Infection with SARS-CoV-2 (virus detection by means of a PCR test not older than 72 hours) Bipulmonary infiltrates (detection by means of X-rays or computed tomography) COVID inflammation score ≥ 10 Ferritin concentration (serum or plasma) ≥ 500 ng / ml Arterial oxygen saturation ≤ 93% when breathing room air written informed consent from the patient Potentially childbearing women: negative pregnancy test Exclusion Criteria (in medical history): Contraindications study medication: Hypersensitivity to the active substance infliximab (or any of the other ingredients of the medicine) or to other murine proteins active or latent tuberculosis acute or chronic hepatitis B severe infections such as invasive fungal infections, bacterial sepsis, or abscesses opportunistic infections (e.g. pneumocystosis, listeriosis) moderate or severe heart failure (NYHA class III / IV) Immunosuppression (e.g. organ transplantation, AIDS, leukopenia) Malignancies or lymphoproliferative diseases or chemotherapy within the last 4 weeks Multiple sclerosis or peripheral demyelinating diseases, including the Guillain-Barré syndrome Treatment with other biologics for therapy for approved indications of infliximab (e.g. for rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, psoriasis) Further exclusion criteria: Autoimmune disease with biologics therapy Current treatment with TNF antibodies, convalescent plasma, bamlanivimab, or other experimental treatments for COVID-19 High-flow oxygen therapy, non-invasive / invasive ventilation (WHO-COVID-19 PROGRESSION Scale > 5) pre-existing long-term ventilation or home oxygen therapy Child-Pugh C liver cirrhosis Pregnancy or breastfeeding Patients with a life expectancy < 90 days due to other medical conditions Limitation or discontinuation of therapy (e.g. refusal of artificial ventilation) Participation in another interventional study Previous participation in this study Interdependence between the patient and the coordinating investigator or other members of the study team
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sina M Coldewey, Prof. Dr. Dr. med.
Organizational Affiliation
Department of Anaesthesiology and Intensive Care Medicine, Jena University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Andreas Stallmach, Prof. Dr. med.
Organizational Affiliation
Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Universitätsklinikum Knappschaftskrankenhaus Bochum
City
Bochum
ZIP/Postal Code
44892
Country
Germany
Facility Name
Klinikum Fulda
City
Fulda
ZIP/Postal Code
36043
Country
Germany
Facility Name
Universitätsklinikum Hamburg-Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Jena University Hospital
City
Jena
ZIP/Postal Code
07747
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
36056419
Citation
Coldewey SM, Neu C, Bloos F, Baumbach P, Schumacher U, Bauer M, Reuken P, Stallmach A. Infliximab in the treatment of patients with severe COVID-19 (INFLIXCOVID): protocol for a randomised, controlled, multicentre, open-label phase II clinical study. Trials. 2022 Sep 2;23(1):737. doi: 10.1186/s13063-022-06566-5.
Results Reference
derived

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Infliximab in the Treatment of Patients With Severe COVID-19 Disease

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