Welte T, Dellinger RP, Ebelt H, et al. Intensive Care Med. 2018; 44: 438-48.
Study Question: In patients with severe community-acquired pneumonia (sCAP) requiring mechanical ventilation (MV), is trimodulin efficacious and safe?
Study Description: This multicenter, randomized, placebo-controlled, phase II trial was conducted in Germany, Spain, and the UK. Patients were randomized to receive intravenous infusions of either trimodulin (a polyclonal antibody preparation containing 23% IgM, 21% IgA, and 56% IgG) based on IgM content (42 mg IgM/kg) or placebo once daily for five consecutive days. Study specific guidance on MV, weaning procedures, and antibiotic treatments were provided to all study sites. The primary endpoint was ventilator-free days (VFDs) and the secondary endpoints included 28-day all-cause and pneumonia-related mortality, time from admission to ICU discharge, hospital length of stay, and vasopressor-free days. Safety assessments included monitoring of treatment-emergent adverse events, infusion-related reactions, vital signs, and pertinent laboratory values. Exploratory post hoc analyses were performed on four identified subsets: high C-reactive protein (CRP ≥70 mg/L), low IgM (≤0.8 g/L), combined high CRP/low IgM, and high procalcitonin (PCT ≥2 ng/mL) baseline levels.
Results: Of the 160 randomized patients, 81 received trimodulin and 79 received placebo. There was no statistically significant difference for VFDs between trimodulin and placebo (11 days vs. 9.6 days, p = 0.173) as well as any of the secondary endpoints and safety assessments. There was a significant increase in VFDs in trimodulin patients across all post-hoc subsets. Additionally, trimodulin treated patients demonstrated a significant absolute reduction in 28-day all-cause mortality for high CRP (16.7%), low IgM (16.6%), and combined high CRP/low IgM (24.8%) measurements.
Conclusion(s): Treatment with trimodulin as adjunctive therapy for patients with sCAP was not more efficacious than placebo.
Perspective: The CIGMA study attempted to demonstrate the efficacy of a novel adjunctive agent in addition to standard treatment to improve outcomes in patients with sCAP. Although trimodulin did not demonstrate a significant difference, the post hoc analyses identified subsets of patients who may benefit from this treatment and a phase III trial is underway to confirm these results.