Antimicrobial-impregnated central venous catheters for preventing neonatal bloodstream infection: the PREVAIL RCT.

BACKGROUND

Clinical trials show that antimicrobial-impregnated central venous catheters reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is insufficient evidence for use in newborn babies.

OBJECTIVES

The objectives were (1) to determine clinical effectiveness by conducting a randomised controlled trial comparing antimicrobial-impregnated peripherally inserted central venous catheters with standard peripherally inserted central venous catheters for reducing bloodstream or cerebrospinal fluid infections (referred to as bloodstream infections); (2) to conduct an economic evaluation of the costs, cost-effectiveness and value of conducting additional research; and (3) to conduct a generalisability analysis of trial findings to neonatal care in the NHS.

DESIGN

Three separate studies were undertaken, each addressing one of the three objectives. (1) This was a multicentre, open-label, pragmatic randomised controlled trial; (2) an analysis was undertaken of hospital care costs, lifetime cost-effectiveness and value of information from an NHS perspective; and (3) this was a retrospective cohort study of bloodstream infection rates in neonatal units in England.

SETTING

The randomised controlled trial was conducted in 18 neonatal intensive care units in England.

PARTICIPANTS

Participants were babies who required a peripherally inserted central venous catheter (of 1 French gauge in size).

INTERVENTIONS

The interventions were an antimicrobial-impregnated peripherally inserted central venous catheter (coated with rifampicin-miconazole) or a standard peripherally inserted central venous catheter, allocated randomly (1 : 1) using web randomisation.

MAIN OUTCOME MEASURE

Study 1 - time to first bloodstream infection, sampled between 24 hours after randomisation and 48 hours after peripherally inserted central venous catheter removal. Study 2 - cost-effectiveness of the antimicrobial-impregnated peripherally inserted central venous catheter compared with the standard peripherally inserted central venous catheters. Study 3 - risk-adjusted bloodstream rates in the trial compared with those in neonatal units in England. For study 3, the data used were as follows: (1) case report forms and linked death registrations; (2) case report forms and linked death registrations linked to administrative health records with 6-month follow-up; and (3) neonatal health records linked to infection surveillance data.

RESULTS

Study 1, clinical effectiveness - 861 babies were randomised (antimicrobial-impregnated peripherally inserted central venous catheter,

LIMITATIONS

The trial was open label as antimicrobial-impregnated and standard peripherally inserted central venous catheters are different colours. There was insufficient power to determine differences in rifampicin resistance.

CONCLUSIONS

No evidence of benefit or harm was found of peripherally inserted central venous catheters impregnated with rifampicin-miconazole during neonatal care. Interventions with small effects on bloodstream infections could be cost-effective over a child's life course. Findings were generalisable to neonatal units in England. Future research should focus on other types of antimicrobial impregnation of peripherally inserted central venous catheters and alternative approaches for preventing bloodstream infections in neonatal care.

TRIAL REGISTRATION

Current Controlled Trials ISRCTN81931394.

FUNDING

This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in

Babies who are born too early or who are very sick require intensive care after birth and during early life. Most will have a long, narrow, plastic tube, called a catheter, inserted into a vein. The catheter is used to give babies fluids containing medicines and nutrition to keep them well and help them grow. The catheter can remain in place for several days or weeks. But the presence of plastic tubing in the vein increases the risk of infection. This study aimed to find out whether or not catheters coated with antimicrobial medicines, called rifampicin and miconazole, could reduce the risk of infection. These medicines act by stopping germs from growing on the catheter, but do not harm the baby or interfere with other treatments. A randomised controlled trial was carried out in 18 neonatal units in England. Whenever a baby needed a catheter, their parents were asked for consent to participate in the trial. The baby was then randomised, similar to tossing a coin, to receive either the antimicrobial catheter or a standard one. A total of 861 babies participated. We followed up all babies in the same way until after the catheter was removed to compare how often babies in each group had an infection. It was found that antimicrobial catheters were no better or worse at preventing infection than standard catheters. Antimicrobial catheters cost more and we found no evidence of benefit; these results suggest that their use in neonatal intensive care is not justified. It was calculated that further research on ways to reduce infection may be good value for money, depending on the costs of this research. The babies who took part in this study were typical of babies in England receiving catheters, meaning that the results can be applied across the NHS. Future research should focus on catheters that contain other types of antimicrobials and alternative ways of preventing infection.