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Eur J Med Res
. 2024 Aug 13;29(1):418.
doi: 10.1186/s40001-024-02008-x. Efficacy and safety of trimodulin in patients with severe COVID-19: results from a randomised, placebo-controlled, double-blind, multicentre, phase II trial (ESsCOVID)
Alina Agafina 1 , Valeria Cristina Aguiar 2 , Maria Rossovskaya 3 , Muriel Sarah Fartoukh 4 , Ludhmila Abrahao Hajjar 5 , Guillaume Thiéry 6 , Jean-François Timsit 7 , Ivan Gordeev 8 , Denis Protsenko 9 , Javier Carbone 10 , Rita Pellegrini 11 , Claudio Marcel Berdun Stadnik # 12 , Sergey Avdeev 13 , Miquel Ferrer 14 , Corina C Heinz 15 , Thomas Häder 15 , Patrick Langohr 15 , Iris Bobenhausen 15 , Jörg Schüttrumpf 15 16 , Alexander Staus 15 , Markus Ruehle 15 , Sabrina Weissmüller 15 , Andrea Wartenburg-Demand 15 , Antoni Torres 17
Affiliations
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 × 109/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.
Keywords: COVID-19; Early systemic inflammation; Immunoglobulin; Immunomodulation; Trimodulin.
. 2024 Aug 13;29(1):418.
doi: 10.1186/s40001-024-02008-x. Efficacy and safety of trimodulin in patients with severe COVID-19: results from a randomised, placebo-controlled, double-blind, multicentre, phase II trial (ESsCOVID)
Alina Agafina 1 , Valeria Cristina Aguiar 2 , Maria Rossovskaya 3 , Muriel Sarah Fartoukh 4 , Ludhmila Abrahao Hajjar 5 , Guillaume Thiéry 6 , Jean-François Timsit 7 , Ivan Gordeev 8 , Denis Protsenko 9 , Javier Carbone 10 , Rita Pellegrini 11 , Claudio Marcel Berdun Stadnik # 12 , Sergey Avdeev 13 , Miquel Ferrer 14 , Corina C Heinz 15 , Thomas Häder 15 , Patrick Langohr 15 , Iris Bobenhausen 15 , Jörg Schüttrumpf 15 16 , Alexander Staus 15 , Markus Ruehle 15 , Sabrina Weissmüller 15 , Andrea Wartenburg-Demand 15 , Antoni Torres 17
Affiliations
- PMID: 39138518
- PMCID: PMC11321023
- DOI: 10.1186/s40001-024-02008-x
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 × 109/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.
Keywords: COVID-19; Early systemic inflammation; Immunoglobulin; Immunomodulation; Trimodulin.