Chlorhexidine-Alcohol Versus Povidone Iodine-Alcohol, Combined or Not With Use of a Bundle of New Devices, for Prevention of Intravascular-catheter Colonization and Catheter Failure (CLEAN3)

Skin Antisepsis With Chlorhexidine-Alcohol Versus Povidone Iodine-Alcohol, Combined or Not With Use of a Bundle of New Devices, for Prevention of Intravascular-catheter Colonization and Catheter Failure: An Open Label, Single Center, Randomized Controlled, Two-by-two Factorial Trial

Short peripheral intravenous catheters (PVC) are the most frequently used invasive medical devices in hospitals. Unfortunately, PVCs often fail before the end of treatment due to the occurrence of complications, which can be mechanical, vascular or infectious. Complications lead to infusion failure and device replacement, which results in interrupted therapy, pain associated with resiting and increased health care costs for resources and staff time. Catheter related bloodstream infections (CR-BSIs) prolong hospitalization and increase treatment costs and mortality.

Prevention of these complications is based on the respect of hygiene rules and the use of bio-compatible catheters. The choice of the antiseptic solution for skin disinfection is key. Similarly, the use of new technologies such as catheters designed to minimize blood exposure, zero-reflux needleless-connectors, disinfecting caps, and flushing PVCs before and after each medication administration to maintain catheter patency are of theoretical interest, but little scientific data support their use in routine.

The primary objectives of this study are, first, to demonstrate that skin preparation with 2% chlorhexidine (CHG)-70% isopropanol decreases the risk of PVC colonization compared to skin preparation with 5% povidone iodine (PVI)-69% ethanol. Second, to demonstrate that use of a bundle of technologies including a new PVC, zero-reflux needless-connectors, disinfecting caps, and single-use prefilled flush syringes extends the time between catheter insertion and catheter failure.

The secondary objectives are to compare between the four study group incidence of phlebitis, accidental catheter removal, infiltration, catheter occlusion, CR-BSI, local infection, all-cause bloodstream infections, catheter colonization, duration of catheter remaining in place without complication, length of hospital stay, safety and patient satisfaction.

The CLEAN 3 study is an open-label, single centre, investigator-initiated, randomised, four-parallel group, two-by-two factorial trial. Patients requiring PVC for an expected 48 h will be randomised in one of four groups according to skin disinfection method and type of devices used. Randomization will be carried out through a secure web-based randomization system. Inclusions are expected to begin in January 2019 and continue until July 2019, once the number of catheters required has been reached.

Patients will be enrolled at the Emergency department of the Poitiers University Hospital before being hospitalised in one of five wards (neurology, neurology, pneumology, internal medicine and downstream emergency unit).

Study Overview

• Status: Completed
• Conditions: Intravascular-catheter Colonization; Catheter Failure
• Intervention / Treatment: Drug: Povidone-Iodine-Alcohol; Device: Insyte Autoguard BC Winged; Drug: Chlorhexidine-Alcohol; Device: Nexiva single port catheter, MaxZero needless connector, PureHub Deinfecting Caps and Posiflush prefilled saline syringes

• Study Type: Interventional
• Enrollment (Actual): 1000
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Poitiers, France, 86021
    • University Hospital of Poitiers

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult (age ≥ 18 years) patients,
• Having clinical indication for placement of a single PVC for at least 48 hours (no minimum port access during the study duration),
• Willing and able to provide informed consent.

Exclusion Criteria:

• Known allergies to CHG, PVI, isopropanol or ethanol,
• Participation to another clinical trial aimed at reducing PVC complications,
• Suspicion of bloodstream infection at catheter insertion,
• Skin injury a catheter insertion site increasing the risk of catheter infection,
• PVC inserted extremely urgently, making it impossible to comply with the protocol,
• Intravascular catheter in place within the last 2 days, or within the last 2 weeks and with local signs of catheter complication,
• Difficult catheter insertion suspected (obesity, known IV drug users, non-visible venous network after placement of a tourniquet...),
• Patients already enrolled in this study,
• Terminal or moribund patient not expected to live more than one week,
• Patients not benefiting from a Social Security scheme or not benefiting from it through a third party,
• Persons benefiting from enhanced protection, namely minors, persons deprived of their liberty by a judicial or administrative decision, adults under legal protection.
• Pregnant or breastfeeding women
• Women at age to procreate and not using effective contraception

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: PVI et Insyte; Groupe A: (1) 5% (w/v) PVI-69% (v/v) ethanol (Bétadine alcoolique™, MEDA Pharma SAS); (2) InsyteTM AutoguardTM BC Winged, BD	Drug: Povidone-Iodine-Alcohol; Povidone-Iodine-Alcohol will be used to disinfect the skin; Device: Insyte Autoguard BC Winged; Pose of Insyte Autoguard BC Winged
EXPERIMENTAL: CHG et Insyte; Groupe B: (1) 2% (w/v) CHG-70% (v/v) isopropanol (ChloraPrep™, CareFusion); (2) InsyteTM AutoguardTM BC Winged, BD	Device: Insyte Autoguard BC Winged; Pose of Insyte Autoguard BC Winged; Drug: Chlorhexidine-Alcohol; Chlorhexidine-Alcohol will be used to disinfect the skin
EXPERIMENTAL: PVI et Nexiva; Groupe C: (1) 5% (w/v) PVI-69% (v/v) ethanol (Bétadine alcoolique™, MEDA Pharma SAS); (2) NexivaTM single port catheter, MaxZeroTM needleless connector, , PureHub™ Desinfecting Caps, PosiflushTM prefilled saline syringes, all from BD	Drug: Povidone-Iodine-Alcohol; Povidone-Iodine-Alcohol will be used to disinfect the skin; Device: Nexiva single port catheter, MaxZero needless connector, PureHub Deinfecting Caps and Posiflush prefilled saline syringes; Pose of Nexiva single port catheter
EXPERIMENTAL: CHG et Nexiva; Groupe D: (1) 2% (w/v) CHG-70% (v/v) isopropanol (ChloraPrep™, CareFusion); (2) NexivaTM single port catheter, MaxZeroTM needleless connector, PureHub™ Desinfecting Caps, PosiflushTM prefilled saline syringes, all from BD	Drug: Chlorhexidine-Alcohol; Chlorhexidine-Alcohol will be used to disinfect the skin; Device: Nexiva single port catheter, MaxZero needless connector, PureHub Deinfecting Caps and Posiflush prefilled saline syringes; Pose of Nexiva single port catheter

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of catheter-related infectious complications	Incidence of catheter-related infectious complications, and include catheter colonisation, local infection and CR-BSI	8 days
Time between catheter insertion and catheter failure	Time between catheter insertion and catheter failure: defined as any premature removal of PVC before end of treatment, other than for routine replacement, and includes phlebitis, infiltration, occlusion, accidental catheter removal, local infection and CR-BSI whichever occurred first	8 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of phlebitis	Number of phlebitis defined as two or more of the following present simultaneously: (1) patient-reported pain or tenderness (on questioning, then palpation by the research nurse) with a severity of two or more on a ten-point scale; (2) erythema extending at least 1 cm from the insertion site; (3) swelling, extending at least 1 cm from the insertion site; (4) purulent discharge; or (5) palpable venous cord beyond the intravenous catheter tip	8 days
Number of accidental catheter removal		8 days
Number of infiltration	Number of infiltration, defined as the infusion of non-blistering drug leaking through the normal vascular channel and resulting in the swelling of tissue peripheral to the puncture site	8 days
Number of catheter occlusion	Number of catheter occlusion defined as the inability of the catheter to flush (not able to intravenously inject 1ml of normal saline within 30 s)	8 days
Number of CR-BSI	Number of CR-BSI, defined as (1) at least one positive blood culture from a peripheral vein and (2) clinical signs of infection (ie, fever [body temperature >38°5], hypothermia [body temperature <36°5], chills, or hypotension [Systolic blood pressure <90 mm Hg]) and (3) no other apparent source for the bloodstream infection except the PVC (in situ within 48 h of the bloodstream infection); and (4) a colonized intravenous catheter tip culture with the same organism (same species) as identified in the blood. For commensal micro-organisms (coagulase-negative staphylococci, Corynebacterium spp. [except C. jeikeium], Lactobacillus spp., Bacillus spp. and Propionibacterium spp., or viridans group Streptococcus isolates and C. perfringens) at least two positive blood cultures will be required.	8 days
Number of local infection	Number of local infection, defined as organisms grown from purulent discharge with no evidence of associated bloodstream infection	8 days
Number of all-cause bloodstream infections	Number of all-cause bloodstream infections, defined as any positive blood culture drawn from a peripheral vein while intravenous catheter in situ or for 48 h after removal. For commensal micro-organisms (coagulase-negative staphylococci, Corynebacterium spp. [except C. jeikeium], Lactobacillus spp., Bacillus spp. and Propionibacterium spp., or viridans group Streptococcus isolates and C. perfringens) at least two positive blood cultures will be required	8 days
Number of catheter colonization	Number of catheter colonization defined as the culture of intravascular catheter tip showing at least 1000 colony-forming units per ml (cfu/ml).	8 days
Number of pathogens involved in catheter colonization, local infections, CR-BSI and all-cause bloodstream infections		8 days
Number of days the catheter remaining in place without complication		8 days
Length of Hospital stay censored at day 28		28 days
Incidence of local and systemic side effects possibly linked to antiseptic use		8 days
Patient's evaluation of the pain at the insertion of the catheter using visual analogue scale (VAS)	Visual analogue scale is increased from 0 to 10, 0 is the better outcome (no pain) and 10 is the worse outcome	8 days
Patient's satisfaction at catheter removal using visual analogue scale (VAS)	Visual analogue scale is increased from 0 to 10, 0 is the worse outcome (no satisfaction) and 10 is the better outcome	8 days
Evaluation impact of venous line on patients' mobility at catheter removal using visual analogue scale	Visual analogue scale is increased from 0 to 10, 0 is the better outcome (no impact of patients'mobility) and 10 is the worse outcome	8 days

Collaborators and Investigators

• Sponsor: Poitiers University Hospital

Publications and helpful links

General Publications

• Maunoury F, Drugeon B, Boisson M, Marjanovic N, Couvreur R, Mimoz O, Guenezan J; CLEAN-3 Study. Cost-effectiveness analysis of bundled innovative devices versus standard approach in the prevention of unscheduled peripheral venous catheters removal due to complications in France. PLoS One. 2022 Jun 14;17(6):e0269750. doi: 10.1371/journal.pone.0269750. eCollection 2022.
• Guenezan J, Marjanovic N, Drugeon B, Neill RO, Liuu E, Roblot F, Palazzo P, Bironneau V, Prevost F, Paul J, Pichon M, Boisson M, Frasca D, Mimoz O; CLEAN-3 trial investigators. Chlorhexidine plus alcohol versus povidone iodine plus alcohol, combined or not with innovative devices, for prevention of short-term peripheral venous catheter infection and failure (CLEAN 3 study): an investigator-initiated, open-label, single centre, randomised-controlled, two-by-two factorial trial. Lancet Infect Dis. 2021 Jul;21(7):1038-1048. doi: 10.1016/S1473-3099(20)30738-6. Epub 2021 Feb 1. Erratum In: Lancet Infect Dis. 2021 Apr 6;:
• Guenezan J, Drugeon B, O'Neill R, Caillaud D, Senamaud C, Pouzet C, Seguin S, Frasca D, Mimoz O. Skin antisepsis with chlorhexidine-alcohol versus povidone iodine-alcohol, combined or not with use of a bundle of new devices, for prevention of short-term peripheral venous catheter-related infectious complications and catheter failure: an open-label, single-centre, randomised, four-parallel group, two-by-two factorial trial: CLEAN 3 protocol study. BMJ Open. 2019 Apr 2;9(4):e028549. doi: 10.1136/bmjopen-2018-028549.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 7, 2019
• Primary Completion (ACTUAL): September 27, 2019
• Study Completion (ACTUAL): September 27, 2019

Study Registration Dates

• First Submitted: November 27, 2018
• First Submitted That Met QC Criteria: November 27, 2018
• First Posted (ACTUAL): November 28, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 31, 2019
• Last Update Submitted That Met QC Criteria: October 30, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Chlorhexidine; Povidone Iodine; Skin antisepsis; Intravascular-catheter colonization; Catheter failure; Bundle of new devices
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Disinfectants; Plasma Substitutes; Blood Substitutes; Ethanol; Chlorhexidine; Povidone-Iodine; Povidone
• Other Study ID Numbers: CLEAN3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No