Efficacy Study Comparing 2% Chlorhexidine in 70% Isopropyl Alcohol Versus 2% Aqueous Chlorhexidine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01270776
Recruitment Status : Unknown
Verified May 2013 by Vibhuti Shah, Mount Sinai Hospital, Canada.
Recruitment status was:  Recruiting
First Posted : January 5, 2011
Last Update Posted : May 14, 2013
The Physicians' Services Incorporated Foundation
Information provided by (Responsible Party):
Vibhuti Shah, Mount Sinai Hospital, Canada

Brief Summary:

The purpose of this study is to compare the efficacy of two different antiseptic solutions (2%chlorhexidine in 70% alcohol with 2% aqueous chlorhexidine)when used in a standardized controlled manner in cleansing the skin of infants with birth weight less than 1500 grams prior to a skin breaking procedure (venepuncture).

The investigators hypothesize that the use of limited amount of 2% aqueous chlorhexidine solution will be as effective as the same amount of 2% chlorhexidine in 70% alcohol for skin antisepsis and that limited exposure to 2% aqueous CHG may be associated with less adverse skin reactions.

Literature from adults has shown that both 2% chlorhexidine in 70% alcohol as well as 2% aqueous chlorhexidine can provide effective skin antisepsis though alcohol containing solution had more long lasting effect. It is also well known from many case reports that alcohol containing products when used to clean abdominal skin for neonatal procedures can cause severe skin damage in preterm infants. This has lead many neonatal units to adopt aqueous chlorhexidine as the antiseptic agent of choice without robust evidence to support its use or standardization of method of application.Both these solutions are widely used in neonatal intensive care units across the globe including Canada.

By conducting this trial, the investigators want to evaluate the efficacy and safety of 2% aqueous chlorhexidine as an antiseptic agent when used in a controlled manner [limited amount for short duration].

Condition or disease Intervention/treatment Phase
Anti-infecting Agents, Local Drug: 2% aqueous chlorhexidine Drug: 2% Chlorhexidine 70% isopropyl alcohol Not Applicable

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Detailed Description:

Venepuncture, either to obtain blood samples for laboratory investigations or to place peripheral intravascular catheters, is an integral part of care in neonatal intensive care units (NICUs). In sick neonates, apart for collection of blood samples venous cannulation is necessary for provision of total parenteral nutrition and administration of medications; however, these skin-breaking procedures places them at risk for local and systemic infectious complications. Bacterial organisms inhabited on the skin travel through the insertion site into the catheter tract and colonize the catheter tip. This is postulated to be a common route of infection for peripherally inserted catheters, hence the need for maintaining optimal skin antisepsis during such procedures.

It is not possible to completely sterilize the skin; however skin antisepsis aims to reduce the number of viable resident organisms on or in the skin and to destroy pathogenic organisms that may be on the skin. Several antiseptic agents are available for skin preparation including 70% alcohol, chlorhexidine (with 70% alcohol or aqueous) and povidone-iodine (PI). Most of the studies comparing the efficacy to these agents have been conducted in adults while there is paucity of studies regarding their use in VLBW infants.

Chlorhexidine, one of the most commonly used biocide antiseptic product, is a broad spectrum bactericidal agent. It diffuses through the outer cell wall and then attacks the bacterial cytoplasmic or inner membrane leading to cell death. Chlorhexidine is active against common gram negative and gram positive pathogens as well as yeast. Numerous randomized controlled trials have been performed in adult patients supporting the superiority of chlorhexidine as skin disinfectant. One of the more influential studies was conducted by Hibbard et al in 2002. The investigators compared 70% isopropyl alcohol; 2% CHG in 70% alcohol; and 2% aqueous CHG in healthy volunteers by obtaining abdominal and inguinal skin swabs at various time points after application. They concluded that all three solutions had excellent and comparable immediate antimicrobial action at 10 minutes & 6 hours after application but 2% CHG in 70% alcohol had better persistent action with antisepsis effectiveness at 24 hours. To date, this is the only study that has compared 2% CHG with and without alcohol directly.

Even though all the above mentioned solutions have proven excellent safety profile in adults, there are significant concerns with their use in preterm neonates. The skin of the newborn infant, especially the preterm infant, is more susceptible to damage from antiseptic agents. Iodine preparations have been associated with transient suppression of thyroid function related to systemic absorption. Alcohol and iodine have been reported to be associated with severe skin injury including blistering, burns and sloughing. Systemic absorption of chlorhexidine is rare, although it has been reported to occur when alcohol is used concurrently. These adverse events have only been reported when these solutions were used for placements of umbilical lines presumably because larger surface area of skin is exposed to a greater quantity of solution for longer duration. Also during such procedures the solution can often get pooled over abdominal skin if used in excessive quantity. No serious adverse event has ever been reported during venepuncture (from either form of chlorhexidine). Such significant concerns with the use of iodine and alcohol containing solutions and more widespread availability of aqueous chlorhexidine has led many NICU's to endorse its use without systematically evaluating its efficacy in this population or standardization of method of application. Therefore, it is important to conduct a well designed study to systematically evaluate the effectiveness of using a limited amount of 2% aqueous CHG in clinical practice.

This double blind planned non-inferiority randomized controlled trial will compare the efficacy and safety of 2% chlorhexidine in 70% isopropyl alcohol (current standard of practice in the NICU) to 2% aqueous chlorhexidine (investigational agent) for skin antisepsis prior to venepuncture in very low birth weight (VLBW, birth weight < 1,500 grams) infants. The effectiveness (success) of skin antisepsis will be assessed by collecting pre- and post- cleansing skin swabs. The skin swabs will then be cultured in the microbiology laboratory and pre- and post- microbial growth will be compared between the two groups.

Changes to the study protocol:

  1. Results of the interim analysis:

    Following the pre-planned interim analysis, it is shown that the initial assumption of standard solution clearance rate used for sample size calculation (92%) was higher than the rate actually observed in the dataset collected up to the interim analysis stage by the investigators (84%). With the assumption of 84% clearance rate for standard solution, the study would have required a bigger sample size of 231 subjects in each arm. With the interim data, the two groups show exactly the same rates of clearance (84%) but with wide confidence intervals for the clearance rate estimates due to smaller sample size. Based on this interim analysis we do not statistically show non-inferiority of the test solution to standard solution. However to obtain a definitive answer we now need to modify our sample size to 462 subjects (231 subjects per arm).

  2. This will now be a multi-center study. We have added SickKids, Toronto as an additional site for recruitment. We have obtained REB approval from SickKids.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 462 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Comparison of 2% Chlorhexidine in 70% Isopropyl Alcohol Versus 2% Aqueous Chlorhexidine for Skin Antisepsis Prior to Venepuncture in Very Low Birth Weight Infants: A Planned Non-inferiority Trial
Study Start Date : January 2011
Estimated Primary Completion Date : January 2014
Estimated Study Completion Date : January 2014

Arm Intervention/treatment
Experimental: Aqueous Chlorhexidine
The group received skin antisepsis using 2% aqueous chlorhexidine solution.
Drug: 2% aqueous chlorhexidine
A single application of a swabstick impregnated with the antiseptic solution over the desired area. The imparted solution will be allowed to air dry with a minimum time of 30 seconds before intervention.
Other Name: SOLU-I.V. Aqueous Swabsticks
Active Comparator: 2% Chlorhexidine 70% isopropyl alcohol
The group will receive skin antisepsis with 2% chlorhexidine solution in alcohol.
Drug: 2% Chlorhexidine 70% isopropyl alcohol
single application of a swabstick impregnated with the antiseptic solution over the desired area. The imparted solution will be allowed to air dry with a minimum time of 30 seconds before intervention.
Other Name: SOLU-I.V. Swabsticks

Primary Outcome Measures :
  1. Bacterial colony count as assessed by pre- and post cleansing skin swab culture. [ Time Frame: 24 hours ]
    A sterile cotton swab with be rolled 4 times across the sampling area. The swab will be broken off into tube containing 1ml of sterile normal saline. A 0.1ml aliquot of this solution will be spread onto a blood agar plate. Colony forming units (CFU) will be enumerated after aerobic incubation at 37°C for 24 hours. Swabs which yield CFU > 15 will be labeled positive for bacteria and negative if CFU < 15.

Secondary Outcome Measures :
  1. Immediate or late Skin reactions. [ Time Frame: 24 hours ]
    Local adverse events will be recorded by researcher at 10 minutes after the procedure and then again at 2, 12 and 24 hours later to monitor for immediate and late local reactions. Adverse events will be recorded using a validated contact dermatitis score.

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 28 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Birth weight < 1500 grams
  • Postnatal age > 48 hours and < 28 days
  • Need for venepuncture for any medical indication

Exclusion Criteria:

  • Birth weight ≥ 1500 grams
  • Infants with skin breakdown or previously documented to have skin reactions to antiseptic agent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01270776

Contact: Vibhuti Shah, MD MRCP 001-416-586-4800 ext 4816
Contact: Amish Jain, MD MRCPCH 001-416-454-3013

Canada, Ontario
Mount Sinai Hospital Recruiting
Toronto, Ontario, Canada, M5G 1X5
Contact: Vibhuti Shah, MD MRCP    001-416-586-4800 ext 4816   
Contact: Amish Jain, MRCPCH (UK)    001-416-454-3013   
Principal Investigator: Vibhuti Shah, MD MRCP         
Sponsors and Collaborators
Mount Sinai Hospital, Canada
The Physicians' Services Incorporated Foundation
Study Chair: Vibhuti Shah, MD MRCP Mount Sinai Hospital, New York

Baumgartner C, Constant H, Putet G, Aulagner G. Cutaneous antiseptic efficacy of two ethanol chlorhexidine dilutions for neonatal venepuncture. Journal De Pharmacie Clinique 1998;17:109-12.
Lilley C, Powls A, Gray A. A prospective randomised double blind Comparison of 0.5% versus 0.05% aqueous Chlorhexidine for skin antisepsis prior to line insertion in neonates. Arch. Dis. Child. 2006;91;17-19.

Responsible Party: Vibhuti Shah, Staff Neonatologist, Mount Sinai Hospital, Canada Identifier: NCT01270776     History of Changes
Other Study ID Numbers: 10 - 0112 - E
First Posted: January 5, 2011    Key Record Dates
Last Update Posted: May 14, 2013
Last Verified: May 2013

Keywords provided by Vibhuti Shah, Mount Sinai Hospital, Canada:
Randomized Controlled Trial
Infant, Premature

Additional relevant MeSH terms:
Pharmaceutical Solutions
Chlorhexidine gluconate
Anti-Infective Agents, Local
Anti-Infective Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Dermatologic Agents