Treatment of COVID-19 Patients With Anti-interleukin Drugs

• Status: Completed
• Trial end date: 2021-04-12
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to test the safety and effectiveness of individually or simultaneously blocking IL-6 and IL-1 versus standard of care on blood oxygenation and systemic cytokine release syndrome in patients with COVID-19 coronavirus infection and acute hypoxic respiratory failure and systemic cytokine release syndrome

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Ghent
• Collaborator: Belgium Health Care Knowledge Centre
• Treatments: Antibodies, Monoclonal; Interleukin 1 Receptor Antagonist Protein; Siltuximab

Criteria

Inclusion Criteria:

• Recent ( ≥ 6 days of flu-like symptoms or malaise yet ≤16 days of flu-like symptoms or malaise prior to randomization) infection with COVID-19.

• Confident COVID-19 diagnosis confirmed by antigen detection test and/or PCR and/or positive serology, or any emerging and validated diagnostic laboratory test for COVID-19 within this period.

• In some patients, it may be impossible to get a confident laboratory confirmation of COVID-19 diagnosis after 24h of hospital admission because viral load is low and/or problems with diagnostic sensitivity. In those cases, in absence of an alternative diagnosis, and with highly suspect bilateral ground glass opacities on recent (<24h) chest-CT scan (confirmed by a radiologist and pulmonary physician as probable COVID-19), and a typical clinical and chemical diagnosis with signs of cytokine release syndrome, a patient can be enrolled as probable COVID-19 infected. In all cases, this needs confirmation by later seroconversion.

• Presence of hypoxia defined as PaO2/FiO2 below 350 while breathing room air in upright position or PaO2/FiO2 below 280 on supplemental oxygen and immediately requiring high flow oxygen device or mechanical ventilation

• signs of cytokine release syndrome defined as ANY of the following:

1. serum ferritin concentration >1000 mcg/L and rising since last 24h

2. single ferritin above 2000 mcg/L in patients requiring immediate high flow oxygen device or mechanical ventilation

3. lymphopenia defined as <800 lymphocytes/microliter) and two of the following extra criteria

• Ferritin > 700 mcg/L and rising since last 24h

• increased LDH (above 300 IU/L) and rising last 24h

• D-Dimers > 1000 ng/mL and rising since last 24h

• CRP above 70mg/L and rising since last 24h and absence of bacterial infection

• if three of the above are present at admission, no need to document 24h rise

• Chest X-ray or CT scan showing bilateral infiltrates within last 2 days

• Admitted to specialized COVID-19 ward or an ICU ward taking care of COVID-19 patients

• Age ≥ 18yrs

• Male or Female

• Willing and able to provide informed consent or legal representative willing to provide informed consent

Exclusion Criteria:

• Patients with known history of serious allergic reactions, including anaphylaxis, to any of the study medications, or any component of the product.

• mechanical ventilation > 24 h at Randomization

• Patient on ECMO at time of screening

• clinical frailty scale above 3 (This frailty score is the patient status before first symptoms of COVID-19 episode.)

• active bacterial or fungal infection

• unlikely to survive beyond 48h

• neutrophil count below 1500 cells/microliter

• platelets below 50.000/microliter

• Patients enrolled in another investigational drug study

• patients on high dose systemic steroids (> 20 mg methylprednisolone or equivalent) for COVID-19 unrelated disorder

• patients on immunosuppressant or immunomodulatory drugs

• patients on current anti-IL1 or anti-IL6 treatment

• signs of active tuberculosis

• serum transaminase levels >5 times upper limit of normal

• bowel perforation or diverticulitis

• pregnant or breastfeeding females (all female subjects deemed of childbearing potential by the investigator must have negative pregnancy test at screening)

• Women of childbearing potential must have a negative serum pregnancy test pre-dose on day 1. Woùmen of childbearing potential must consistently and correctly use (during the entire treatment period and 3 months after last reatment) 1 highly effective method for contraception.