title: CATheter Infections in CHildren (CATCH): a randomised controlled trial and economic evaluation comparing impregnated and standard central venous catheters in children.
abstract: BACKGROUND
  Impregnated central venous catheters (CVCs) are recommended for adults to reduce bloodstream infection (BSI) but not for children.
  
  
  OBJECTIVE
  To determine the effectiveness of impregnated compared with standard CVCs for reducing BSI in children admitted for intensive care.
  
  
  METHODS
  Multicentre randomised controlled trial, cost-effectiveness analysis from a NHS perspective and a generalisability analysis and cost impact analysis.
  
  
  METHODS
  14 English paediatric intensive care units (PICUs) in England.
  
  
  METHODS
  Children aged < 16 years admitted to a PICU and expected to require a CVC for ≥ 3 days.
  
  
  METHODS
  Heparin-bonded, antibiotic-impregnated (rifampicin and minocycline) or standard polyurethane CVCs, allocated randomly (1 : 1 : 1). The intervention was blinded to all but inserting clinicians.
  
  
  METHODS
  Time to first BSI sampled between 48 hours after randomisation and 48 hours after CVC removal. The following data were used in the trial: trial case report forms; hospital administrative data for 6 months pre and post randomisation; and national-linked PICU audit and laboratory data.
  
  
  RESULTS
  In total, 1859 children were randomised, of whom 501 were randomised prospectively and 1358 were randomised as an emergency; of these, 984 subsequently provided deferred consent for follow-up. Clinical effectiveness - BSIs occurred in 3.59% (18/502) of children randomised to standard CVCs, 1.44% (7/486) of children randomised to antibiotic CVCs and 3.42% (17/497) of children randomised to heparin CVCs. Primary analyses comparing impregnated (antibiotic and heparin CVCs) with standard CVCs showed no effect of impregnated CVCs [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.37 to 1.34]. Secondary analyses showed that antibiotic CVCs were superior to standard CVCs (HR 0.43, 95% CI 0.20 to 0.96) but heparin CVCs were not (HR 1.04, 95% CI 0.53 to 2.03). Time to thrombosis, mortality by 30 days and minocycline/rifampicin resistance did not differ by CVC. Cost-effectiveness - heparin CVCs were not clinically effective and therefore were not cost-effective. The incremental cost of antibiotic CVCs compared with standard CVCs over a 6-month time horizon was £1160 (95% CI -£4743 to £6962), with an incremental cost-effectiveness ratio of £54,057 per BSI avoided. There was considerable uncertainty in costs: antibiotic CVCs had a probability of 0.35 of being dominant. Based on index hospital stay costs only, antibiotic CVCs were associated with a saving of £97,543 per BSI averted. The estimated value of health-care resources associated with each BSI was £10,975 (95% CI -£2801 to £24,751). Generalisability and cost-impact - the baseline risk of BSI in 2012 for PICUs in England was 4.58 (95% CI 4.42 to 4.74) per 1000 bed-days. An estimated 232 BSIs could have been averted in 2012 using antibiotic CVCs. The additional cost of purchasing antibiotic CVCs for all children who require them (£36 per CVC) would be less than the value of resources associated with managing BSIs in PICUs with standard BSI rates of > 1.2 per 1000 CVC-days.
  
  
  CONCLUSIONS
  The primary outcome did not differ between impregnated and standard CVCs. However, antibiotic-impregnated CVCs significantly reduced the risk of BSI compared with standard and heparin CVCs. Adoption of antibiotic-impregnated CVCs could be beneficial even for PICUs with low BSI rates, although uncertainty remains whether or not they represent value for money to the NHS. Limitations - inserting clinicians were not blinded to allocation and a lower than expected event rate meant that there was limited power for head-to-head comparisons of each type of impregnation. Future work - adoption of impregnated CVCs in PICUs should be considered and could be monitored through linkage of electronic health-care data and clinical data on CVC use with laboratory surveillance data on BSI.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01029717.
  
  
  BACKGROUND
  This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 18. See the NIHR Journals Library website for further project information.
authors.affiliation: Institute of Child Health, University College London, London, UK.
authors.forename: Katie
authors.initials: K
authors.lastname: Harron
authors.affiliation: Great Ormond Street Hospital, London, UK.
authors.forename: Quen
authors.initials: Q
authors.lastname: Mok
authors.affiliation: Medicines for Children Clinical Trials Unit, University of Liverpool, Liverpool, UK.
authors.forename: Kerry
authors.initials: K
authors.lastname: Dwan
authors.affiliation: Centre for Health Economics and Medicines Evaluation, Bangor University, Bangor, UK.
authors.forename: Colin H
authors.initials: CH
authors.lastname: Ridyard
authors.affiliation: Medicines for Children Clinical Trials Unit, University of Liverpool, Liverpool, UK.
authors.forename: Tracy
authors.initials: T
authors.lastname: Moitt
authors.affiliation: Barts Health NHS Trust, London, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Millar
authors.affiliation: Great Ormond Street Hospital, London, UK.
authors.forename: Padmanabhan
authors.initials: P
authors.lastname: Ramnarayan
authors.affiliation: Evelina London Children's Hospital, London, UK.
authors.forename: Shane M
authors.initials: SM
authors.lastname: Tibby
authors.affiliation: Healthcare Associated Infection and Antimicrobial Resistance (HCAI & AMR) Department, National Infection Service, Public Health England, London, UK.
authors.forename: Berit
authors.initials: B
authors.lastname: Muller-Pebody
authors.affiliation: Centre for Health Economics and Medicines Evaluation, Bangor University, Bangor, UK.
authors.forename: Dyfrig A
authors.initials: DA
authors.lastname: Hughes
authors.affiliation: Medicines for Children Clinical Trials Unit, University of Liverpool, Liverpool, UK.
authors.forename: Carrol
authors.initials: C
authors.lastname: Gamble
authors.affiliation: Institute of Child Health, University College London, London, UK.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Gilbert
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D055499:Catheter-Related Infections / Q000097:blood / Q000517:prevention & control*; D062905:Central Venous Catheters / Q000009:adverse effects* / Q000191:economics; D002648:Child; D002675:Child, Preschool; D003362:Cost-Benefit Analysis; D004739:England; D005260:Female; D006493:Heparin; D006801:Humans; D015278:Intensive Care Units, Pediatric / Q000191:economics; D008297:Male; D008911:Minocycline / Q000008:administration & dosage; D012293:Rifampin / Q000008:administration & dosage; D013222:State Medicine
chemical_list: D000900:Anti-Bacterial Agents; D006493:Heparin; D008911:Minocycline; D012293:Rifampin