Randomized Trial of 2% Chlorhexidine-70% Isopropanol vs 5% Povidone Iodine-69% Ethanol for Skin Antisepsis in Reducing Surgical-site Infection After Cardiac Surgery (CLEAN2)

An Open Label, Multicenter, Randomized Trial of 2% Chlorhexidine-70% Isopropanol vs 5% Povidone Iodine-69% Ethanol for Skin Antisepsis in Reducing Surgical-site Infection After Cardiac Surgery

Despite completion of more than 9 million procedures each year in France, the best antiseptic solution to be used for preparing the skin to reduce risk of surgical site infection (SSI) remains unknown. 2% Chlorhexidine gluconate (CHG)-alcohol is superior to Povidone Iodine (PVI)-alcohol for short term vascular catheter care (Mimoz O, Lancet 2015; Pages J, Intensive Care Med 2016), but studies comparing both antiseptic solutions for clean-contaminated surgical procedures led to conflicting results.

The present study will be the first large scale multicenter randomized controlled trial adequately powered to compare efficacy and safety of CHG-alcohol over PVI-alcohol in reducing SSI after clean surgery.

A clean surgery was chosen because pathogens involved in SSI mostly originate from skin. Therefore, optimisation of skin disinfection before surgery has the potential to reduce the incidence of SSI. Cardiac surgery was chosen because SSI may be severe, diagnosis of SSI is easy to monitor and to define and infections arise earlier than other frequent clean surgeries using implants such as orthopaedic or vascular surgery.

The incidence of reoperation for any purpose will be used as the main objective because there are easy to track and define and are less susceptible to interpretation in an open trial than superficial SSI. According to CDC criteria, patients will be monitored up to Day 90 because mediastinitis after cardiac surgery may occur after the usual 30-day SSI surveillance period.

Study Overview

• Status: Completed
• Conditions: Cardiac Surgery in Adult Patient
• Intervention / Treatment: Drug: 2%Chlorhexidine-70%Isopropanol; Drug: 5%Povidone Iodine- 69%Ethanol

• Study Type: Interventional
• Enrollment (Actual): 3316
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63100
    • University Hospital of Clermont-Ferrand
  • Nantes, France, 44000
    • University Hospital of Nantes
  • Paris, France, 75013
    • La Pitié Salpêtrière Hospital
  • Paris, France, 75014
    • Institut Mutualiste Montsouris
  • Poitiers, France, 86021
    • University Hospital of Poitiers
  • Rennes, France
    • University Hospital of Rennes
  • Strasbourg, France, 67091
    • CHRU de Strasbourg
  • Toulouse, France, 31400
    • CHU de Toulouse

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 patients (age ≥ 18 years)
• Undergoing any (scheduled) surgery of the heart (valve, coronary or combined surgery) or of the aorta via a median sternotomy
• Having given their informed consent

Exclusion Criteria:

• Patients with known allergies to CHG, PVI, isopropanol or ethanol
• Surgery for heart transplantation
• Any signs of inflammation or sternal instability at the site of sternotomy or operation for infection (SWI or endocarditis)
• Patients with history of cardiac surgery within 3 months preceding enrolment
• Participation to another clinical trial aimed at reducing SSI
• Patients already enrolled in this study
• Pregnant or breastfeeding women
• Women at age to procreate and not using effective contraception
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chlorhexidine Group	Drug: 2%Chlorhexidine-70%Isopropanol; 2% Chlorhexidine-70% isopropanol will be used to disinfect the skin before Cardiac Surgery and during all dressing changes
Active Comparator: Povidone Iodine Group	Drug: 5%Povidone Iodine- 69%Ethanol; 5%Povidone Iodine- 69%Ethanol will be used to disinfect the skin before Cardiac Surgery and during all dressing changes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of any re-sternotomy occurring between Day 0 and Day 90 after surgery	90 days
Incidence of any reoperation on saphen venous/radial artery site occurring between Day 0 and Day 30 after surgery.	30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of mediastinitis according to CDC criteria occurring by Day 90 after surgery and pathogens involved	90 days
Incidence of deep incisional SSIs at saphen venous/radial artery site according to CDC criteria occurring by Day 30 after surgery and pathogens involved	30 days
Incidence of superficial incisional SSIs at sternal or saphen venous/radial artery sites according to CDC criteria occurring by Day 30 after surgery and pathogens involved	30 days
Incidence of SWI requiring reoperation, occurring by Day 90	90 days
Incidence of SSIs at saphen venous/radial artery site requiring reoperation, occurring by Day 30	30 days
Incidence of unexpected need for re-admission to the ICU or re-hospitalisation	90 days
Number of days in ICU	90 days
Number of days under mechanical ventilation	90 days
Number of days in Hospital	90 days
Number of days in rehabilitation unit	90 days
Mortality at Day 90 of surgery	90 days
Incidence of local and systemic side effects possibly linked to antiseptic use	90 days
Economic analysis including cost-effectiveness of surgical skin antisepsis	90 days

Collaborators and Investigators

• Sponsor: Poitiers University Hospital

Publications and helpful links

General Publications

• Boisson M, Corbi P, Kerforne T, Camilleri L, Debauchez M, Demondion P, Eljezi V, Flecher E, Lepelletier D, Leprince P, Nesseler N, Nizou JY, Roussel JC, Rozec B, Ruckly S, Lucet JC, Timsit JF, Mimoz O. 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. BMJ Open. 2019 Jun 17;9(6):e026929. doi: 10.1136/bmjopen-2018-026929.

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2018
• Primary Completion (Actual): May 25, 2022
• Study Completion (Actual): May 25, 2022

Study Registration Dates

• First Submitted: May 24, 2018
• First Submitted That Met QC Criteria: June 15, 2018
• First Posted (Actual): June 18, 2018

Study Record Updates

• Last Update Posted (Actual): June 13, 2022
• Last Update Submitted That Met QC Criteria: June 10, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Chlorhexidine; Surgical site infection; Povidone Iodine; Skin antisepsis
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Wound Infection; Infections; Surgical Wound Infection; 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: CLEAN2

Drug and device information, study documents

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