No registrations found.
ID
Source
Brief title
Health condition
COVID-19 with Hypoxia
Sponsors and support
Intervention
Outcome measures
Primary outcome
30-day mortality (from randomization)
Secondary outcome
- To asses in a randomized comparison days in hospital (calculated from randomisation).
- To asses in a randomized comparison the percentage of patients who need ICU care.
- To asses in a randomized comparison the percentage of patients who develop respiratory failure and need mechanical ventilation.
- To asses in a randomized comparison the days on a ventilator.
- To asses in a randomized comparison normalisation of HRCT after resolution of disease.
- To asses in a randomized comparison seroconversion 14 days after randomisation
- To identify potential biomarkers predictive of response (blood: cytokines (including Il-6 and IL-18), lymphopenia, CRP, ferritin, LDH, sCD25; nasal epithelial brushes: epithelial transcriptome immune response by bulk and single-cell RNA seq; faeces: microbiome, viral load), gender, age, co-morbidity and plasma levels tocilizumab by exploratory analysis.
- To assess safety and feasibility of pre-emptive use of tocilizumab (AE grade ≥4).
- To assess in a randomized comparison OS after 3 months (after randomization).
Background summary
This trial aims to develop an effective treatment strategy for COVID-19 patients with hypoxia OR other signs of hyperinflammation (ferritin >2000 μg/L or doubling of serum ferritin in 20-48 hours). The rationale for tocilizumab is: 1) Patients with respiratory failure caused by COVID-19 have a dismal prognosis; 2) The hyper inflammatory state in COVID-19 patients is a main reason for respiratory insufficiency and dead; 3) Tocilizumab is an effective drug to control cytokine storms without hampering the functional immune response; 4) Extensive experience is present with tocilizumab in the clinical setting with cytokine release syndromes (e.g. after CAR-T cell therapy).
The rationale to apply tocilizumab in the pre-emptive phase i.e. at the moment of hypoxia (defined according to cytokine release syndrome (CRS) grade II), or other signs of hyperinflammation (ferritin >2000 μg/L or doubling of serum ferritin in 20-48 hours), is to modulate the cytokine storm at an early phase before the phase of respiratory failure is reached. This is in line with the early application of tocilizumab in the clinical setting to modulate cytokine storms after CAR-T cell therapy.
Study objective
Based on literature we assume a 20% day 30 mortality of patients admitted to the hospital ward with COVID-19. We aim to lower this day 30 mortality to 10%.
Study design
at entry, prior to first infusion, and 24h, 72h, 1 week, 2 weeks, 3 months after first infusion
Intervention
Patients in this study are treated with intravenous tociluzumab: 8 mg/kg (maximum dose 800 mg), which can be repeated at the same dose after 8 hours if the hypoxia has not improved. This is the approved dose for cytokine release syndrome.
Inclusion criteria
♦ Patients 18 years and older
♦ Patients with a diagnosis of COVID-19 based on a compatible clinical presentation AND a positive SARS-CoV-2 PCR on a respiratory sample such as a nasopharyngeal swab, sputum, or BAL fluid
♦ Clinical features compatible with hyperinflammation:
- Hypoxia, without other explanation for hypoxia than COVID-19 OR
- ferritin >2000 μg/L or doubling of serum ferritin in 20-48 hours
Hypoxia is defined according to ASTCT CRS Consensus grading: grade II. [Lee DW, et al. BBMT 2019;25(4):625-638] Inclusion of patients already requiring oxygen administration prior to COVID-19 should be discussed with the study team.
♦ Written informed consent.
♦ Patient is capable of giving informed consent.
Exclusion criteria
♦ Pregnancy
♦ allergy to tocilizumab
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL8504 |
| Other | METc UMCG : METc 2020/172 |