Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study).

PURPOSE: The CIGMA study investigated a novel human polyclonal antibody preparation (trimodulin) containing ~ 23% immunoglobulin (Ig) M, ~ 21% IgA, and ~ 56% IgG as add-on therapy for patients with severe community-acquired pneumonia (sCAP). METHODS: In this double-blind, phase II study (NCT01420744), 160 patients with sCAP requiring invasive mechanical ventilation were randomized (1:1) to trimodulin (42 mg IgM/kg/day) or placebo for five consecutive days. Primary endpoint was ventilator-free days (VFDs). Secondary endpoints included 28-day all-cause and pneumonia-related mortality. Safety and tolerability were monitored. Exploratory post hoc analyses were performed in subsets stratified by baseline C-reactive protein (CRP; ≥ 70 mg/L) and/or IgM (≤ 0.8 g/L). RESULTS: Overall, there was no statistically significant difference in VFDs between trimodulin (mean 11.0, median 11 [n = 81]) and placebo (mean 9.6; median 8 [n = 79]; p = 0.173). Twenty-eight-day all-cause mortality was 22.2% vs. 27.8%, respectively (p = 0.465). Time to discharge from intensive care unit and mean duration of hospitalization were comparable between groups. Adverse-event incidences were comparable. Post hoc subset analyses, which included the majority of patients (58-78%), showed significant reductions in all-cause mortality (trimodulin vs. placebo) in patients with high CRP, low IgM, and high CRP/low IgM at baseline. CONCLUSIONS: No significant differences were found in VFDs and mortality between trimodulin and placebo groups. Post hoc analyses supported improved outcome regarding mortality with trimodulin in subsets of patients with elevated CRP, reduced IgM, or both. These findings warrant further investigation. TRIAL REGISTRATION: NCT01420744.

[Survival of haematologic patients admitted to an Intensive Care Unit. A 16 years study]. / Supervivencia de los pacientes con hemopatías ingresados en una Unidad de Medicina Intensiva. Estudio de 16 años.

BACKGROUND AND OBJECTIVE: The survival of haematologic patients admitted to Intensive Care units (ICU) is so poor, that it is debatable whether they should be admitted or not to them. We aimed to find out the survival of these patients in an ICU to know if their admission is justified. PATIENTS AND METHOD: Retrospective study of 600 haematologic patients (49.4 ± 16.4 years, 58.3% male) representing a total of 660 different admissions to the ICU of a university hospital, with a 6 months follow-up. Haematologic diseases were: leukaemia (50.5%), lymphoma (18.7%), myeloma (10.0%), myelodysplasic syndromes (4.2%), aplastic anaemia or bone marrow aplasia (3.3%), thrombotic microangiopathies and HELLP syndrome (7.4%), and others. RESULTS: A total of 37.5% of patients survived. Survival of thrombotic microangiopathies and HELLP syndrome was higher (81.8% of patients) than that of leukaemias (26.6%) and lymphomas (49.1%). When the reason for ICU admission was respiratory failure with or without septic shock, the survival was lower (20 and 27% of admissions respectively) than when it was septic shock alone (58.7%). Survival of mechanically ventilated patients was 14.6%, that of those treated with any renal replacement therapy 32.4% and that of patients with both treatments 13.8%. From all mechanically ventilated leukaemia or lymphoma patients, 10.3% survived (93 days in the ICU per life saved) but only 7.7% were alive 6 months later. CONCLUSIONS: Considering that the ICU survival was higher than 10% for all the groups studied, we conclude that admission of haematologic patients to the ICU is appropriate.