title: Skin antisepsis with chlorhexidine-alcohol versus povidone iodine-alcohol, with and without skin scrubbing, for prevention of intravascular-catheter-related infection (CLEAN): an open-label, multicentre, randomised, controlled, two-by-two factorial trial.
abstract: BACKGROUND
  Intravascular-catheter-related infections are frequent life-threatening events in health care, but incidence can be decreased by improvements in the quality of care. Optimisation of skin antisepsis is essential to prevent short-term catheter-related infections. We hypothesised that chlorhexidine-alcohol would be more effective than povidone iodine-alcohol as a skin antiseptic to prevent intravascular-catheter-related infections.
  
  
  METHODS
  In this open-label, randomised controlled trial with a two-by-two factorial design, we enrolled consecutive adults (age ≥18 years) admitted to one of 11 French intensive-care units and requiring at least one of central-venous, haemodialysis, or arterial catheters. Before catheter insertion, we randomly assigned (1:1:1:1) patients via a secure web-based random-number generator (permuted blocks of eight, stratified by centre) to have all intravascular catheters prepared with 2% chlorhexidine-70% isopropyl alcohol (chlorhexidine-alcohol) or 5% povidone iodine-69% ethanol (povidone iodine-alcohol), with or without scrubbing of the skin with detergent before antiseptic application. Physicians and nurses were not masked to group assignment but microbiologists and outcome assessors were. The primary outcome was the incidence of catheter-related infections with chlorhexidine-alcohol versus povidone iodine-alcohol in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01629550 and is closed to new participants.
  
  
  RESULTS
  Between Oct 26, 2012, and Feb 12, 2014, 2546 patients were eligible to participate in the study. We randomly assigned 1181 patients (2547 catheters) to chlorhexidine-alcohol (594 patients with scrubbing, 587 without) and 1168 (2612 catheters) to povidone iodine-alcohol (580 patients with scrubbing, 588 without). Chlorhexidine-alcohol was associated with lower incidence of catheter-related infections (0·28 vs 1·77 per 1000 catheter-days with povidone iodine-alcohol; hazard ratio 0·15, 95% CI 0·05-0·41; p=0·0002). Scrubbing was not associated with a significant difference in catheter colonisation (p=0·3877). No systemic adverse events were reported, but severe skin reactions occurred more frequently in those assigned to chlorhexidine-alcohol (27 [3%] patients vs seven [1%] with povidone iodine-alcohol; p=0·0017) and led to chlorhexidine discontinuation in two patients.
  
  
  CONCLUSIONS
  For skin antisepsis, chlorhexidine-alcohol provides greater protection against short-term catheter-related infections than does povidone iodine-alcohol and should be included in all bundles for prevention of intravascular catheter-related infections.
  
  
  BACKGROUND
  University Hospital of Poitiers, CareFusion.
authors.affiliation: Service d'Anesthésie et de Réanimation, CHU de Poitiers, Poitiers, France; Université de Poitiers, UFR de Médecine Pharmacie, Poitiers, France; INSERM U1070, Pharmacologie des Agents antiInfectieux, Poitiers, France. Electronic address: olivier.mimoz@chu-poitiers.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Mimoz
authors.affiliation: AP-HP, Bichat University Hospital, Infection Control Unit, Paris, France; INSERM, UMR 1137-IAME Team 5-DeSCID: Decision Sciences in Infectious Diseases, Control and Care, Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Lucet
authors.affiliation: Service d'Anesthésie et de Réanimation, CHU de Poitiers, Poitiers, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kerforne
authors.affiliation: Service de Réanimation Adultes et Unité de Surveillance Continue, CHU Clermont Ferrand, Clermont Ferrand, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Pascal
authors.affiliation: Service de Réanimation médicale, CHU Clermont Ferrand, Clermont-Ferrand, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Souweine
authors.affiliation: Service de Réanimation Médicale, CHU de Poitiers, Poitiers, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Goudet
authors.affiliation: Département de Réanimation Médicale et Médecine Hyperbare, CHU d'Angers, Angers, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Mercat
authors.affiliation: INSERM, UMR 1137-IAME Team 5-DeSCID: Decision Sciences in Infectious Diseases, Control and Care, Paris, France; University Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Lila
authors.initials: L
authors.lastname: Bouadma
authors.affiliation: Service de Réanimation Chirurgicale, CHU d'Angers, Angers, France.
authors.forename: Sigismond
authors.initials: S
authors.lastname: Lasocki
authors.affiliation: Service de Réanimation et Maladies infectieuses, CH de Tourcoing, Tourcoing, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Alfandari
authors.affiliation: Service d'Anesthésie et de Réanimation Médicale et Chirurgicale, CHU Lyon-Sud, Lyon, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Friggeri
authors.affiliation: Service d'Anesthésie et de Réanimation Médicale et Chirurgicale, CHU Lyon-Sud, Lyon, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Wallet
authors.affiliation: Service de Réanimation Chirurgicale, Hôpital Bichat-Claude-Bernard, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Allou
authors.affiliation: OutcomeRéa, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Ruckly
authors.affiliation: Service d'Anesthésie et de Réanimation, CHU de Poitiers, Poitiers, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Balayn
authors.affiliation: Service d'Anesthésie et de Réanimation Médicale et Chirurgicale, CHU Lyon-Sud, Lyon, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Lepape
authors.affiliation: INSERM, UMR 1137-IAME Team 5-DeSCID: Decision Sciences in Infectious Diseases, Control and Care, Paris, France; University Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Timsit
mesh_terms: D000368:Aged; D000891:Anti-Infective Agents, Local / Q000627:therapeutic use*; D000985:Antisepsis / Q000379:methods*; D055499:Catheter-Related Infections / Q000517:prevention & control*; D002405:Catheterization, Central Venous / Q000379:methods; D002406:Catheterization, Peripheral / Q000379:methods; D002408:Catheters, Indwelling; D002710:Chlorhexidine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D000431:Ethanol / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011206:Povidone-Iodine / Q000627:therapeutic use*; D016896:Treatment Outcome; D062666:Vascular Access Devices
chemical_list: D000891:Anti-Infective Agents, Local; D000431:Ethanol; D011206:Povidone-Iodine; D002710:Chlorhexidine