Role of the Funding Source The PROHIBIT study was funded by the European Commission 7th Framework Program. The study funder had no role in the study design, data collection, data analysis, data interpretation, or writing of the manuscript. The study funder was not involved in the decision to submit the paper for publication. RESULTS Participating hospitals Fifteen hospitals were selected from 18 applicants to provide an even geographical distribution across Europe. Two hospitals dropped out before study start: one due to local ethics review board requiring individual written informed consent from patients, and one due to the workload anticipated by the ICU as non‐feasible. One hospital was excluded during baseline because it failed to comply with the study protocol. Two of the three drop‐out hospitals were replaced. Fourteen hospitals from 11 European countries completed the study: four were randomized to HHi, five to CVCi, and five to COMBi. Seven hospitals were university‐affiliated. Four centers counted >50,000 admissions per year, four between 30,000 and 50,000, and five <30,000. The median (range) number of ICU beds per hospital was 30 (10‐53). Median nurse‐to‐patient ratio in the ICU was 0.42 (0.25‐1). Median (interquartile range (IQR)) activity index was 10.7 (8.2‐12.7) hand hygiene opportunities per hour. Patients and CVC utilization A total of 35,831 CVCs and 25,348 patients were included in the study. Patient and CVC characteristics are summarized in Tables 1 (per study arm) and Supp. Table 2 (overall). Patient and CVC characteristics differed significantly among the three intervention arms (Table 1). The APACHE II and SAPS II scores were available for only 35% and 37% of patients, respectively (Supp Table 3); and therefore excluded from the main analysis. CVC utilization decreased in all three intervention arms, but significantly only in the CVCi arm (Supp. Table 3). Median CVC dwell‐times decreased in the COMBi arm (6 to 5 days, p<0.0001), but did not change significantly in the HHi‐ (6 and 7 days, p=0.41) and CVCi arms (5 and 5 days, p=0.46). CRBSI incidence densities The overall CRBSI incidence density decreased from 2.4/1000 CVC‐days at baseline to 0.9/1000 during the intervention (rate ratio, 0.39; 95% CI, 0.32–0.48; p<0.0001). CRBSI incidences at baseline differed significantly between the three study arms: 2.0, 1.4, and
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