Eculizumab as an emergency treatment for adult patients with severe COVID-19 in the intensive care unit: A proof-of-concept study.
EClinicalMedicine
; 28: 100590, 2020 Nov.
Article
in En
| MEDLINE
| ID: mdl-33173853
ABSTRACT
BACKGROUND:
Complement pathway inhibition may provide benefit for severe acute respiratory illnesses caused by viral infections such as COVID-19. We present results from a nonrandomized proof-of-concept study of complement C5 inhibitor eculizumab for treatment of severe COVID-19.METHODS:
All patients (N = 80) with confirmed SARS-CoV-2 infection and severe COVID-19 admitted to our intensive care unit between March 10 and May 5, 2020 were included. Forty-five patients were treated with standard care and 35 with standard care plus eculizumab through expanded-access emergency treatment. The prespecified primary outcome was day-15 survival. Clinical laboratory values and biomarkers, complement levels, and treatment-emergent serious adverse events (TESAEs) were also assessed.FINDINGS:
At day 15, estimated survival was 82.9% (95% CI 70.4%â95.3%) with eculizumab and 62.2% (48.1%â76.4%) without eculizumab (log-rank test, P = 0.04). Patients treated with eculizumab experienced a significantly more rapid decrease in lactate, blood urea nitrogen, total and conjugated bilirubin levels and a significantly more rapid increase in platelet count, prothrombin time, and in the ratio of arterial oxygen tension over fraction of inspired oxygen versus patients treated without eculizumab. Eculizumab-associated changes in complement levels, laboratory values, and biomarkers were consistent with terminal complement inhibition, reduced hypoxia, and decreased inflammation. TESAEs of special interest occurring in >5% of patients treated with/without eculizumab were ventilator-associated pneumonia (51%/24%), bacteremia (11%/2%), gastroduodenal hemorrhage (14%/16%), and hemolysis (3%/18%).INTERPRETATION:
Findings from this proof-of-concept study suggest eculizumab may improve survival and reduce hypoxia in patients with severe COVID-19. Randomized studies evaluating the efficacy and safety of this treatment approach are needed.FUNDING:
Programme d'Investissements d'Avenir ANR-18-RHUS60004.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Clinical_trials
Language:
En
Journal:
EClinicalMedicine
Year:
2020
Document type:
Article