Efficacy and safety of trimodulin in patients with severe COVID-19: results from a randomised, placebo-controlled, double-blind, multicentre, phase II trial (ESsCOVID).

Autor: Agafina A; City Hospital, St Petersburg, Russia., Aguiar VC; Science Valley Research Institute, São Paulo, Brazil., Rossovskaya M; City Clinical Hospital, Moscow, Russia., Fartoukh MS; Assistance Publique-Hôpitaux de Paris, Service de Médecine Intensive Réanimation, Hôpital Tenon, and DMU APPROCHES, Sorbonne Université, Paris, France., Hajjar LA; Instituto Do Coração InCor, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Thiéry G; CHU Saint-Etienne, Saint-Priest-en-Jarez, France., Timsit JF; Medical and Infectious Diseases ICU (M12) APHP, Hôpital Bichat-Claude Bernard, Paris, France., Gordeev I; City Clinical Hospital #15, Moscow, Russia., Protsenko D; City Clinical Hospital #40, Moscow, Russia., Carbone J; Hospital General Universitario Gregorio Marañon, Madrid, Spain., Pellegrini R; Pesquisare, Santo André, Brazil., Stadnik CMB; Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil., Avdeev S; First Moscow State Medical University, Moscow, Russia., Ferrer M; Hospital Clinic of Barcelona, IDIBAPS, CibeRes (CB06/06/0028) University of Barcelona, Barcelona, Spain., Heinz CC; Biotest AG, Dreieich, Germany., Häder T; Biotest AG, Dreieich, Germany., Langohr P; Biotest AG, Dreieich, Germany., Bobenhausen I; Biotest AG, Dreieich, Germany., Schüttrumpf J; Biotest AG, Dreieich, Germany.; Grifols SA, Barcelona, Spain., Staus A; Biotest AG, Dreieich, Germany., Ruehle M; Biotest AG, Dreieich, Germany., Weissmüller S; Biotest AG, Dreieich, Germany., Wartenburg-Demand A; Biotest AG, Dreieich, Germany., Torres A; Respiratory and Intensive Care Unit, Hospital Clinic of Barcelona, IDIBAPS, CibeRes (CB06/06/0028), University of Barcelona, Barcelona, Spain. ATORRES@clinic.cat.
Jazyk: angličtina
Zdroj: European journal of medical research [Eur J Med Res] 2024 Aug 13; Vol. 29 (1), pp. 418. Date of Electronic Publication: 2024 Aug 13.
DOI: 10.1186/s40001-024-02008-x
Abstrakt: Background: Trimodulin (human polyvalent immunoglobulin [Ig] M ~ 23%, IgA ~ 21%, IgG ~ 56% preparation) has previously been associated with a lower mortality rate in a subpopulation of patients with severe community-acquired pneumonia on invasive mechanical ventilation (IMV) and with clear signs of inflammation. The hypothesis for the ESsCOVID trial was that trimodulin may prevent inflammation-driven progression of severe coronavirus disease 2019 (COVID-19) to critical disease or even death.
Methods: Adults with severe COVID-19 were randomised to receive intravenous infusions of trimodulin or placebo for 5 consecutive days in addition to standard of care. The primary efficacy endpoint was a composite of clinical deterioration (Days 6-29) and 28-day all-cause mortality (Days 1-29).
Results: One-hundred-and-sixty-six patients received trimodulin (n = 84) or placebo (n = 82). Thirty-three patients died, nine during the treatment phase. Overall, 84.9% and 76.5% of patients completed treatment and follow-up, respectively. The primary efficacy endpoint was reported in 33.3% of patients on trimodulin and 34.1% of patients on placebo (P = 0.912). No differences were observed in the proportion of patients recovered on Day 29, days of invasive mechanical ventilation, or intensive care unit-free days. Rates of treatment-emergent adverse events were comparable. A post hoc analysis was conducted in patients with early systemic inflammation by excluding those with high CRP (> 150 mg/L) and/or D-dimer (≥ 3 mg/L) and/or low platelet counts (< 130 × 10 9 /L) at baseline. Forty-seven patients in the trimodulin group and 49 in the placebo group met these criteria. A difference of 15.5 percentage points in clinical deterioration and mortality was observed in favour of trimodulin (95% confidence interval: -4.46, 34.78; P = 0.096).
Conclusion: Although there was no difference in the primary outcome in the overall population, observations in a subgroup of patients with early systemic inflammation suggest that trimodulin may have potential in this setting that warrants further investigation. ESSCOVID WAS REGISTERED PROSPECTIVELY AT CLINICALTRIALS.GOV ON OCTOBER 6, 2020.: NCT04576728.
(© 2024. The Author(s).)
Databáze: MEDLINE
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