Safety and Efficacy Study of Ethanol Locking to Prevent Central Line Infection in Premature Neonates

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2010 by East Carolina University.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
East Carolina University
ClinicalTrials.gov Identifier:
NCT01365312
First received: May 31, 2011
Last updated: June 2, 2011
Last verified: November 2010
  Purpose

Appropriate delivery of adequate nutrition and medications in premature infants often requires central venous access in the form of a special IV called a PICC (peripherally inserted central catheter). While a necessary feature of neonatal intensive care, PICCs pose significant risk: among the most serious of these is infection. One common, successful infection control practice used in older children and adults involves the use of a lock, in which a fluid-filled syringe is attached to the end of an IV when it is not in use in order to prevent and/or treat clotting or infection. The solution is left for some period of time and is then either withdrawn from the line or flushed into the patient. The solution could be saline, antibiotics, other antiseptics, or any combination of these. However in the premature infant, use of antibiotics as a locking compound risks leaving behind organisms resistant to treatment; antiseptics can irritate vessels and cause breakage to sensitive premature skin; saline has neither sterilization nor anti-infective properties. By contrast, ethanol neutralizes or kills most bacteria, viruses, and fungi without the risk of resistance, and because it is not externally applied there is no risk to baby skin. Ethanol-based lock protocols have been used safely and effectively in both adult and pediatric populations without adverse effects, but this has not been tested in premature babies because fluids and medication are delivered continuously: placement of a lock traditionally requires an extended pause (hours or days) in fluid and medication administration.

To overcome these key limitations, a periodic, brief ethanol lock protocol was designed such that both infant exposure and interruptions to fluid and medication delivery would be minimized. The lock is practical, cheap, easy to place, and takes advantage of an existing daily pause during which IV tubing and fluids hooked up to the PICC are changed. The objective of this study is to test the hypothesis that use of a 70% ethanol lock, every 3rd day, for 15 minutes, will safely and effectively reduce PICC infection in our unit.


Condition Intervention
Infection Associated With Catheter
Bacteremia
Sepsis
Drug: Ethanol lock
Drug: Heparinized saline

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Prospective, Randomized, Blinded, Placebo-Controlled Trial of Periodic, Brief Ethanol Locks to Prevent Peripherally-Inserted Central Catheter (PICC) Infections in Preterm Infants in the Neonatal Intensive Care Unit

Resource links provided by NLM:


Further study details as provided by East Carolina University:

Primary Outcome Measures:
  • Incidence of PICC-related sepsis in infants with ethanol-treated vs. Placebo treated lines [ Time Frame: Study Day #28 or sooner if PICC is discontinued before day #28 ] [ Designated as safety issue: No ]
    Primary endpoint of the study is to compare the incidence of PICC-related sepsis in infants with ethanol treated vs. Placebo treated lines by study day 28. PICC-related sepsis is defined by any 2 clinical signs or symptoms plus one positive peripheral blood culture for a recognized pathogen in this population other than coagulase-negative staphylococcus, or 2 positive peripheral blood cultures for coagulase-negative staphylococcus within 48 hours.


Secondary Outcome Measures:
  • Evaluation of PICC colonization following ethanol locking [ Time Frame: Duration of PICC use, average of 3 weeks ] [ Designated as safety issue: No ]
    PICC colonization is reflected by growth of >15 CFU from a 5-cm segement of the PICC tip by semiquantitative (roll-plate) culture, or growoth of >100 CFU by quantitative (sonication) broth culture in an otherwise asymptomatic patient.

  • Whether the primary and secondary endpoints differ by birthweight strata [ Time Frame: Duration of PICC use, average of 3 weeks ] [ Designated as safety issue: No ]
    Birthweight stratification will use a 3-tiered subset (<1000g, 1000-1250g, and >1250g) consistent with existing neonatal literature.

  • To determine whether ethanol lock treatment impacts incidence of clinical evaluations for suspected sepsis [ Time Frame: Duration of PICC use, average of 3 weeks ] [ Designated as safety issue: No ]
    Other evaluations for suspected sepsis are those not defined by the primary endpoint but meeting criteria for infection of some other sterile body fluid (urine or CSF).

  • To determine whether antibiotic use for any indication (including non-bacteremia) alters the incidence of PICC-related infection or colonization as defined in the primary and secondary endpoints [ Time Frame: Duration of PICC use, average of 3 weeks ] [ Designated as safety issue: No ]
    See above

  • Determine side effects of ethanol locking in premature babies [ Time Frame: Duration of PICC use, average of 3 weeks ] [ Designated as safety issue: Yes ]
    To determine the side effects of flushing ethanol locks into premature infants following lock therapy, if any

  • To determine effect of ethanol locking on neonatal PICC lines [ Time Frame: Duration of PICC use, average of 3 weeks ] [ Designated as safety issue: Yes ]
    To determine how ethanol locking affects central line function and integrity in vivo, if at all.


Estimated Enrollment: 150
Study Start Date: February 2010
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ethanol
Assigned intervention is a 70% ethanol lock, placed every 72 hours for 15 minutes, for the duration of the PICC line.
Drug: Ethanol lock
Placement of 0.5 cc 70% ethanol, every 72 hours, for 15 minutes, into PICC lines randomized to ethanol intervention
Placebo Comparator: Heparinized saline
Intervention is to place a heparinized saline lock every 72 hours for 15 minutes, for the duration of the line.
Drug: Heparinized saline
0.5 cc heparinized saline to be placed once every 72 hours for 15 minutes, in PICC lines randomized to placebo

Detailed Description:

PICC infection is of particular concern in the NICU because of the need for long term intravenous access in many very-low and the majority of extremely-low birthweight infants, the very populations at highest risk for infection in the first place. Central lines are a mainstay of treatment in these babies because of the need for extended parenteral nutrition, which itself has been associated with blood stream infection, not to mention the increased use of anti-infectives, added hospitalization costs, longer length of stay, and negative impact upon nutrition delivery when infectious complications occur.

Existing infection control practices differ by unit and region, and include hand washing, sterile precautions at insertion and dressing changes, elimination of mandatory scheduled dressing changes, minimizing port access to the extent permitted by clinical care, prophylactic antibiotics, and closed medication systems. Success is variable: there is no standard highly effective, safe approach to infection control, and central line infection remains a leading cause of morbidity and mortality in the NICU.

A standard practice to maintain central line patency when it is not in use is to lock it with a syringe containing a heparinized solution. Locks containing antibiotics have been used to prevent infection of central lines and to treat already-infected lines, but this approach confers risk of development of organisms resistant to treatment. External chlorhexidine-impregnated dressings have been used but can harm premature skin and do not achieve sterilization of the lumen or hub, where most infections originate.

Medical grade ethyl alcohol (ethanol) is a widely used compound with uses as a disinfectant, preservative, antidote to ingested ethylene glycol (anti-freeze), and anti-microbial. The FDA lists no specific approval or indication though it's use is widely recognized. Multiple studies have been conducted in sheep, children and adults, using 0.5-2 mL 70% ethanol locks to successfully prevent and/or treat catheter related infection without development of resistant organisms, adverse side effects to patients, or disruptions in catheter integrity. Though the ethanol lock approach has not yet been applied to premature neonates, safe and successful precedent in humans as young as 3 months is established; ours is the first trial of ethanol locking in a NICU setting.

  Eligibility

Ages Eligible for Study:   up to 32 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Preterm infants < 32 weeks gestation at birth who require a PICC

Exclusion Criteria:

  • Any baby with a positive blood culture less than 48 hours prior to PICC placement; any infant who requires pressors in excess of >5 mcg/kg/min
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01365312

Contacts
Contact: Amber E Fort, DO 252-847-9571 forta@ecu.edu
Contact: James J Cummings, MD 252-744-8992 cummingsj@ecu.edu

Locations
United States, North Carolina
East Carolina University Recruiting
Greenville, North Carolina, United States, 27834
Principal Investigator: Amber E Fort, DO         
Sub-Investigator: James J Cummings, MD         
Sponsors and Collaborators
East Carolina University
  More Information

No publications provided

Responsible Party: Amber Fort, DO, MPH, MS, East Carolina University School of Medicine
ClinicalTrials.gov Identifier: NCT01365312     History of Changes
Other Study ID Numbers: NeonatalELT
Study First Received: May 31, 2011
Last Updated: June 2, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by East Carolina University:
Central line associated infection
PICC associated infection
Neonatal central line associated sepsis
Central line colonization
Ethanol Lock

Additional relevant MeSH terms:
Bacteremia
Sepsis
Catheter-Related Infections
Bacterial Infections
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Ethanol
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Central Nervous System Depressants
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2014