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

This study is currently recruiting participants.
Verified May 2013 by Mount Sinai Hospital, Canada
Sponsor:
Collaborator:
The Physicians' Services Incorporated Foundation
Information provided by (Responsible Party):
Vibhuti Shah, Mount Sinai Hospital, Canada
ClinicalTrials.gov Identifier:
NCT01270776
First received: January 4, 2011
Last updated: May 13, 2013
Last verified: May 2013

January 4, 2011
May 13, 2013
January 2011
January 2014   (final data collection date for primary outcome measure)
Bacterial colony count as assessed by pre- and post cleansing skin swab culture. [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
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.
Same as current
Complete list of historical versions of study NCT01270776 on ClinicalTrials.gov Archive Site
Immediate or late Skin reactions. [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
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.
Same as current
Not Provided
Not Provided
 
Efficacy Study Comparing 2% Chlorhexidine in 70% Isopropyl Alcohol Versus 2% Aqueous Chlorhexidine
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

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].

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.
Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Anti-infecting Agents, Local
  • 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
  • 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
  • Experimental: Aqueous Chlorhexidine
    The group received skin antisepsis using 2% aqueous chlorhexidine solution.
    Intervention: Drug: 2% aqueous chlorhexidine
  • Active Comparator: 2% Chlorhexidine 70% isopropyl alcohol
    The group will receive skin antisepsis with 2% chlorhexidine solution in alcohol.
    Intervention: Drug: 2% Chlorhexidine 70% isopropyl alcohol

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
462
January 2014
January 2014   (final data collection date for primary outcome measure)

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
Both
up to 28 Days
No
Contact: Vibhuti Shah, MD MRCP 001-416-586-4800 ext 4816 vshah@mtsinai.on.ca
Contact: Amish Jain, MD MRCPCH 001-416-454-3013 amish.jain@utoronto.ca
Canada
 
NCT01270776
10 - 0112 - E
No
Vibhuti Shah, Mount Sinai Hospital, Canada
Mount Sinai Hospital, Canada
The Physicians' Services Incorporated Foundation
Study Chair: Vibhuti Shah, MD MRCP Mount Sinai Hospital, New York
Mount Sinai Hospital, Canada
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP