Anti-il6 Treatment of Serious COVID-19 Disease With Threatening Respiratory Failure
Keywords
Abstract
Dates
| Last Verified: | 03/31/2020 |
| First Submitted: | 03/23/2020 |
| Estimated Enrollment Submitted: | 03/23/2020 |
| First Posted: | 03/25/2020 |
| Last Update Submitted: | 04/04/2020 |
| Last Update Posted: | 04/06/2020 |
| Actual Study Start Date: | 04/04/2020 |
| Estimated Primary Completion Date: | 05/31/2021 |
| Estimated Study Completion Date: | 05/31/2021 |
Condition or disease
Intervention/treatment
Drug: Roactemra iv
Drug: Roactemra sc
Drug: Kevzara sc
Other: Standard medical care
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: Roactemra iv Single dose treatment with 400 mg tocilizumab intravensously | Drug: Roactemra iv single dose treatment with tocilizumab 400 mg intravenously |
| Experimental: Roactemra sc Single dose treatment with 2 x 162 mg tocilizumab subcutaneously | Drug: Roactemra sc single dose treatment with tocilizumab 2 x 162 mg subcutaneously |
| Experimental: Kevzara sc Single dose treatment with 1 x 200 mg sarilumab subcutaneously | Drug: Kevzara sc single dose treatment with sarilumab 1 x 200 mg subcutaneously |
| Active Comparator: Standard care Management as usual |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: - SARS-CoV-2 infection confirmed by real time-PCR and - Positive imaging: consolidation, ground glass opacities, or bilateral pulmonary infiltration either by CT-scan or chest x-ray; and - Need of oxygen therapy to maintain SO2>94% OR FiO2/PaO2 > 20 and at least two of the following laboratory measures: - CRP level >70 mg/L - CRP level >= 40 mg/L and doubled within 48 hours (without other confirmed infectious or non-infectious course), - Lactatdehydrogenase > 250 U/L, - thrombocytopenia < 120.000 x 10E9/L, - lymphocyte count < 0.6 x 10E9/L, - D-dimer > 1 ug/mL, - serum ferritin > 300 ug/mL Exclusion Criteria: - pregnancy suspected or confirmed, - severe heart failure, - suspected or confirmed bacterial infection, - current solid or hematological malignancy, - neutropenia, - ALAT elevation more than three times the laboratory upper limit, - ASA class 5 (after COVID19 admission) or higher at inclusion (prior admission), - severe chronic obstructive pulmonary disease or heart failure (NYHA class II or higher), - pregnant or lactating women, - current treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs)/immunosuppressive agents including IL-6 inhibitors, or with Janus kinase inhibitors (JAKi) in the past 30 days or plans to receive during the study period, - current use of chronic oral corticosteroids in a dose higher than prednisone 10 mg or equivalent per day, - previous or active tuberculosis (TB), - HIV infection regardless of immunological status, hepatitis, - evidence of recent (30 days) invasive bacterial or fungal infections, - patients who have received immunosuppressive antibody therapy within the past 5 months, including intravenous immunoglobulin or plans to receive during the study period, - IV drug abuse, - history of inflammatory bowel disease, - diverticulitis, - ulcer, - perforated gastrointestinal tract, - participation in any clinical research study evaluating an investigational product (IP) or therapy within 3 months and less than five half-lives of IP prior inclusion to the study, - any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study, - inability to give informed consent. |
Outcome
Primary Outcome Measures
1. Time to independence from supplementary oxygen therapy [days from enrolment up 28 days]
Secondary Outcome Measures
1. Number of deaths [28 days from enrolment]
2. Days out of hospital and alive [28 days from enrolment]
3. Ventilator free days alive and out of hospital [28 days from enrolment]
4. C-reactive protein (CRP) level [baseline]
5. C-reactive protein (CRP) level [peak during hospitalisation, up to 28 days]
6. C-reactive protein (CRP) level [14 days]
7. C-reactive protein (CRP) level [28 days]
8. Number of participants with serious adverse events [During treatment, up to 28 days]
