Antimicrobial-impregnated central venous catheters for prevention of neonatal bloodstream infection (PREVAIL): an open-label, parallel-group, pragmatic, randomised controlled trial
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Abstract
Background Bloodstream infection is associated with high mortality and serious morbidity in preterm babies.
Evidence from clinical trials shows that antimicrobial-impregnated central venous catheters (CVCs) reduce catheterrelated bloodstream infection in adults and children receiving intensive care, but there is a paucity of similar evidence
for babies receiving neonatal intensive care.
Methods This open-label, parallel-group, pragmatic, randomised controlled trial was done in 18 neonatal intensive
care units in England. Newborn babies who needed a peripherally inserted CVC (PICC) were allocated randomly (1:1)
to receive either a PICC impregnated with miconazole and rifampicin or a standard (non-antimicrobial-impregnated)
PICC. Random allocation was done with a web-based program, which was centrally controlled to ensure allocation
concealment. Randomisation sequences were computer-generated in random blocks of two and four, and stratified by
site. Masking of clinicians to PICC allocation was impractical because rifampicin caused brown staining of the
antimicrobial-impregnated PICC. However, participant inclusion in analyses and occurrence of outcome events were
determined following an analysis plan that was specified before individuals saw the unblinded data. The primary
outcome was the time from random allocation to first microbiologically confirmed bloodstream or cerebrospinal fluid
(CSF) infection between 24 h after randomisation and 48 h after PICC removal or death. We analysed outcome data
according to the intention-to-treat principle. We excluded babies for whom a PICC was not inserted from safety
analyses, as these analyses were done with groups defined by the PICC used. This trial is registered with ISRCTN,
number 81931394.
Findings Between Aug 12, 2015, and Jan 11, 2017, we randomly assigned 861 babies (754 [88%] born before 32 weeks
of gestation) to receive an antimicrobial-impregnated PICC (430 babies) or standard PICC (431 babies). The median
time to PICC removal was 8·20 days (IQR 4·77–12·13) in the antimicrobial-impregnated PICC group versus
7·86 days (5·00–12·53) days in the standard PICC group (hazard ratio [HR] 1·03, 95% CI 0·89–1·18, p=0·73), with
46 (11%) of 430 babies versus 44 (10%) of 431 babies having a microbiologically confirmed bloodstream or CSF
infection. The time from random allocation to first bloodstream or CSF infection was similar between the two
groups (HR 1·11, 95% CI 0·73–1·67, p=0·63). Secondary outcomes relating to infection, rifampicin resistance in
positive blood or CSF cultures, mortality, clinical outcomes at neonatal unit discharge, and time to PICC removal
were similar between the two groups, although rifampicin resistance in positive cultures of PICC tips was higher in
the antimicrobial-impregnated PICC group (relative risk 3·51, 95% CI 1·16–10·57, p=0·018). 60 adverse events were
reported from 49 (13%) patients in the antimicrobial-impregnated PICC group and 50 events from 45 (10%) babies
in the standard PICC group.
Interpretation We found no evidence of benefit or harm associated with miconazole and rifampicin-impregnated
PICCs compared with standard PICCs for newborn babies. Future research should focus on other types of
antimicrobial impregnation of PICCs and alternative approaches for preventing infection