Medical News Stories
A Randomized Placebo-Controlled Phase II Study of a Pseudomonas Vaccine in Ventilated Icu Patients
A Randomized Placebo-Controlled Phase II Study of a Pseudomonas Vaccine in Ventilated Icu Patients
Rello, J, Krenn, C, Locker G, et al. Crit Care. 2017;21:22.
Study Question: What is the immunogenicity of various doses of IC43, a vaccine against Pseudomonas, and is it safe and effective in mechanically ventilated ICU patients?
Study Description: This multicenter, phase II, placebo-controlled study sought to evaluate the safety and efficacy of IC43, a
vaccine against Pseudomonas infection, in adult, mechanically ventilated ICU patients. Patients had to have been mechanically ventilated for >48 hours and with a high probability of survival ≥48 hours after randomization. Four groups were evaluated: IC43 100 mcg with and without aluminum hydroxide adjuvant, IC43 200 mcg with adjuvant, and placebo. Vaccination was given on days zero and seven. The primary outcome was the immunogenic response to IC43 assessed at day 14, defined as OprF/I-specific antibody titers. Secondary endpoints included safety, rates of Pseudomonas infection, and mortality.
Results: A total of 401 patients were included, predominantly following medical admissions (77.6%). There was a significant difference in immune response in all IC43 groups on day 14 compared to placebo (p<0.0001). There was a more profound immune response to the 200 mcg dose compared with the 100 mcg dose with adjuvant (p=0.034), but not the 100 mcg dose without adjuvant (p=0.99). Patients receiving the 100 mcg dose without adjuvant experienced the highest rate of seroconversion (80.6%). There was a significantly lower mortality in the IC43 100 mcg without adjuvant group compared to placebo (p= 0.0099). There was no significant difference in P. aeruginosa infection rate or the number of patients receiving antibiotics active against P. aeruginosa, between groups. The incidence of adverse drug events was low and similar between groups and included pulmonary hemorrhage and shock that occurred in 2 patients that received the 100 mcg dose with adjuvant.
Conclusion(s): The results of this study demonstrated that the use of IC43 vaccination in ventilated ICU patients produced a significant immunogenic effect and was well tolerated, but did not result in lower P. aeruginosa infection rates.
Perspective: The production of a vaccination against Pseudomonas species is an attractive development; however, the results of this trial demonstrate that the use of IC43 did not decrease the rate of Pseudomonas infection, although it was not powered to do so. Additionally, the majority of Pseudomonas infections occurred before day 14. The immunogenic response to IC43 was noted to occur between day 7 and 14, thus it is possible that early onset Pseudomonas infections may not be preventable by vaccination. It was demonstrated that an immunogenic response was a significant predictor of mortality, and a phase III trial is currently ongoing to further evaluate IC43.