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.

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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: University Hospital of Poitiers, CareFusion.

Multicentre, open-label, randomised, controlled clinical trial comparing 2% chlorhexidine-70% isopropanol and 5% povidone iodine-69% ethanol for skin antisepsis in reducing surgical-site infection after cardiac surgery: the CLEAN 2 study protocol.

INTRODUCTION: Surgical-site infection (SSI) is the second most frequent cause of healthcare-associated infection worldwide and is associated with increased morbidity, mortality and healthcare costs. Cardiac surgery is clean surgery with low incidence of SSI, ranging from 2% to 5%, but with potentially severe consequences.Perioperative skin antisepsis with an alcohol-based antiseptic solution is recommended to prevent SSI, but the superiority of chlorhexidine (CHG)-alcohol over povidone iodine (PVI)-alcohol, the two most common alcohol-based antiseptic solutions used worldwide, is controversial. We aim to evaluate whether 2% CHG-70% isopropanol is more effective than 5% PVI-69% ethanol in reducing the incidence of reoperation after cardiac surgery. METHODS AND ANALYSIS: The CLEAN 2 study is a multicentre, open-label, randomised, controlled clinical trial of 4100 patients undergoing cardiac surgery. Patients will be randomised in 1:1 ratio to receive either 2% CHG-70% isopropanol or 5% PVI-69% ethanol for perioperative skin preparation. The primary endpoint is the proportion of patients undergoing any re-sternotomy between day 0 and day 90 after initial surgery and/or any reoperation on saphenous vein/radial artery surgical site between day 0 and day 30 after initial surgery. Data will be analysed on the intention-to-treat principle. ETHICS AND DISSEMINATION: This protocol has been approved by an independent ethics committee and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EudraCT 2017-005169-33 and NCT03560193.

Cost-effectiveness analysis of chlorhexidine-alcohol versus povidone iodine-alcohol solution in the prevention of intravascular-catheter-related bloodstream infections in France.

OBJECTIVE: To perform a cost-effectiveness analysis of skin antiseptic solutions (chlorhexidine-alcohol (CHG) versus povidone iodine-alcohol solution (PVI)) for the prevention of intravascular-catheter-related bloodstream infections (CRBSI) in intensive care unit (ICU) in France based on an open-label, multicentre, randomised, controlled trial (CLEAN). DESIGN: A 100-day time semi-markovian model was performed to be fitted to longitudinal individual patient data from CLEAN database. This model includes eight health states and probabilistic sensitivity analyses on cost and effectiveness were performed. Costs of intensive care unit stay are based on a French multicentre study and the cost-effectiveness criterion is the cost per patient with catheter-related bloodstream infection avoided. PATIENTS: 2,349 patients (age≥18 years) were analyzed to compare the 1-time CHG group (CHG-T1, 588 patients), the 4-time CHG group (CHG-T4, 580 patients), the 1-time PVI group (PVI-T1, 587 patients), and the 4-time PVI group (PVI-T4, 594 patients). INTERVENTION: 2% chlorhexidine-70% isopropyl alcohol (chlorhexidine-alcohol) compared to 5% povidone iodine-69% ethanol (povidone iodine-alcohol). RESULTS: The mean cost per alive, discharged or dead patient was of €23,798 (95% confidence interval: €20,584; €34,331), €21,822 (€18,635; €29,701), €24,874 (€21,011; €31,678), and €24,201 (€20,507; €29,136) for CHG-T1, CHG-T4, PVI-T1, and PVI-T4, respectively. The mean number of patients with CRBSI per 1000 patients was of 3.49 (0.42; 12.57), 6.82 (1.86; 17.38), 26.04 (14.64; 42.58), and 23.05 (12.32; 39.09) for CHG-T1, CHG-T4, PVI-T1, and PVI-T4, respectively. In comparison to the 1-time PVI solution, the 1-time CHG solution avoids 22.55 CRBSI /1,000 patients, and saves €1,076 per patient. This saving is not statistically significant at a 0.05 level because of the overlap of 95% confidence intervals for mean costs per patient in each group. Conversely, the difference in effectiveness between the CHG-T1 solution and the PVI-T1 solution is statistically significant. CONCLUSIONS: The CHG-T1 solution is more effective at the same cost than the PVI-T1 solution. CHG-T1, CHG-T4 and PVI-T4 solutions are statistically comparable for cost and effectiveness. This study is based on the data from the RCT from 11 French intensive care units registered with www.clinicaltrials.gov (NCT01629550).

Comparison of four skin preparation strategies to prevent catheter-related infection in intensive care unit (CLEAN trial): a study protocol for a randomized controlled trial.

BACKGROUND: Catheter-related infection is the third cause of infections in intensive care units (ICU), increasing the length of stay in ICU and hospital, mortality, and costs. Skin antisepsis is one of the most prevalent preventive measures. In this respect, it would appear preferable to recommend the use of alcoholic povidone iodine or chlorhexidine rather than aqueous povidone iodine. However, the data comparing chlorhexidine to povidone-iodine, both of them in alcoholic solutions, remain limited. Moreover, the benefits of enhanced cleaning prior to disinfection of skin that is not visibly soiled have yet to be confirmed in a randomized study. METHODS: A prospective multicenter, 2 × 2 factorial, randomized-controlled, assessor-blind trial will be conducted in 11 intensive care units in six French hospitals. All adult patients aged over 18 years requiring the insertion of at least one peripheral arterial catheter and/or a non-tunneled central venous catheter and/or a hemodialysis catheter and/or an arterial pulmonary catheter will be randomly assigned to have all their catheters cared with one of four skin preparation strategies (2% chlorhexidine/70% isopropyl alcohol or 5% povidone iodine/69% ethanol with or without prior skin scrubbing). At catheter removal, catheter tips will be quantitatively cultured. Sets of aerobic and anaerobic blood cultures will be routinely obtained when a patient has fever, hypothermia, or other indications. In case of suspected catheter-related infection the patient's form will be reviewed by an independent adjudication committee. We plan to enroll 2,400 patients (4,800 catheters). The main objective is to demonstrate that use of 2% alcoholic chlorhexidine compared to 5% alcoholic povidone iodine in skin preparation lowers the rate of catheter-related infection. The second endpoint is to demonstrate that enhanced skin cleaning prior to disinfection of skin that is not visibly soiled does not reduce catheter colonization. Other outcomes include comparison of skin colonization at catheter insertion site, comparison of catheter colonization and catheter-related bacteremia taking place during implementation of the four strategies of skin preparation, and cutaneous tolerance, length of hospitalization, mortality, and costs. DISCUSSION: This study will help to update recommendations on the choice of an antiseptic agent to use in skin preparation prior to insertion of a vascular catheter and, by extension, of an epidural catheter and it will likewise help to update recommendations on the usefulness of skin scrubbing prior to disinfection when the skin is not visibly soiled. TRIAL REGISTRATION: Clinicaltrials.gov number NCT01629550.