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

Sepsis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01365312
• Other study ID #: NeonatalELT
• Status: Terminated
• Phase: N/A
• First received: May 31, 2011
• Last updated: October 2, 2014
• Start date: February 2010

Study information

• Verified date: October 2014
• Source: East Carolina University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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 The solution is left for some period of time and is then either withdrawn from the line or flushed into the patient.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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 32 Weeks

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Bacteremia
• Catheter-Related Infections
• Communicable Diseases
• Infection
• Infection Associated With Catheter
• Sepsis

Intervention

Drug:
• Ethanol lock
Placement of 0.5 cc 70% ethanol, every 72 hours, for 15 minutes, into PICC lines randomized to ethanol intervention
• Heparinized saline
0.5 cc heparinized saline to be placed once every 72 hours for 15 minutes, in PICC lines randomized to placebo

Locations

Country	Name	City	State
United States	East Carolina University	Greenville	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
East Carolina University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of PICC-related sepsis in infants with ethanol-treated vs. Placebo treated lines	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.	Study Day #28 or sooner if PICC is discontinued before day #28	No
Secondary	Evaluation of PICC colonization following ethanol locking	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.	Duration of PICC use, average of 3 weeks	No
Secondary	Whether the primary and secondary endpoints differ by birthweight strata	Birthweight stratification will use a 3-tiered subset (<1000g, 1000-1250g, and >1250g) consistent with existing neonatal literature.	Duration of PICC use, average of 3 weeks	No
Secondary	To determine whether ethanol lock treatment impacts incidence of clinical evaluations for suspected sepsis	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).	Duration of PICC use, average of 3 weeks	No
Secondary	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	See above	Duration of PICC use, average of 3 weeks	No
Secondary	Determine side effects of ethanol locking in premature babies	To determine the side effects of flushing ethanol locks into premature infants following lock therapy, if any	Duration of PICC use, average of 3 weeks	Yes
Secondary	To determine effect of ethanol locking on neonatal PICC lines	To determine how ethanol locking affects central line function and integrity in vivo, if at all.	Duration of PICC use, average of 3 weeks	Yes