COVID-19
Conditions
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.
Interventions
DRUGInfliximab
single intravenous administration of 5 milligrams/kilogram
OTHERStandard of Care
Standard of Care
Sponsors
German Federal Ministry of Education and Research
Celltrion
Jena University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 28-day mortality | 28 days after randomization | differences in mortality-rates between both study arms (Infliximab + Standard of Care vs. Standard of Care) 28 days after randomisation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| safety of Infliximab administration | up to 90 days after randomization | 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 | day 7 and day 14 after randomization | 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 | day 7 and day 14 after randomization | 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 | day 7 and day 14 after randomization | 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 | day 28 after randomization | ventilation-free days until 28 days after randomization |
| assessment of the severity and frequency of organ failure: renal replacement therapy-free days | day 28 after randomization | renal replacement therapy-free days until 28 days after randomization |
| assessment of the severity and frequency of organ failure: vasopressor-free days | day 28 after randomization | vasopressor-free days until 28 days after randomization |
| occurence of Acute Respiratory Distress Syndrome (ARDS) | day 28 after randomization | rate of occurrence of ARDS until 28 days after randomization |
| health related quality of life: index | day 90 after randomization | EQ5D-3L: index value 90 days after randomization |
| incidence of cardiomyopathy | day 3 and 7 after randomization | incidence of cardiomyopathy 3 and/or 7 days after randomization |
| WHO-COVID-19-Progression Scale | day 7, 14 and 28 after randomization | WHO-COVID-19-Progression Scale on day 7, 14 and 28 after randomization |
| rate of admission to the intensive care unit | day 28 after randomization | rate of admission to the intensive care unit after randomization up to day 28 |
| length of stay: hospital | day 28 after randomization | length of hospital stay up to day 28 after randomization |
| length of stay: intensive care unit | day 28 after randomization | length of intensive care unit stay up to day 28 after randomization |
| mortality | day 14 and 90 after randomization | mortality rates 14 and 90 days after randomization |
| health related quality of life: visual analogue scale | day 90 after randomization | EQ5D-3L: visual analog scale value 90 days after randomization |
Other
| Measure | Time frame | Description |
|---|---|---|
| collection and storage of blood and urine sample | day 3, 7 and 14 after randomization | 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 |
| comparison with other cohorts | up to day 90 after randomization | comparison of the course of disease of patients with severe COVID-19 and previously generated datasets from patients with sepsis and health subjects |
Countries
Germany
Outcome results
None listed