Study of Biotene OralBalance Gel for Oral Care in Critically-Ill Mechanically Ventilated Neonates

A Randomized Controlled Clinical Trial of Two Different Oral Care Regimens Combined With Ventilator-Associated Pneumonia (VAP) Bundle Strategy for Reduction of Duration of Mechanical Ventilation in a Neonatal Population

The goal of this pilot study is to test the hypothesis that mechanically ventilated infants receiving Biotene OralBalance® gel for oral care would have a reduced intubation time compared to infants receiving oral care placebo. This study is also performed to test the feasibility as well the safety of Biotene OralBalance® gel.

Study Overview

• Status: Completed
• Conditions: Ventilator-associated Pneumonia
• Intervention / Treatment: Drug: Biotene OralBalance® gel; Other: Sterile Water moisten cotton tipped applicator

Detailed Description

Prolonged mechanical ventilation is a known risk factor strongly associated with ventilator-associated pneumonia (VAP). As the fatality rates for VAP are high, prevention of VAP has focused on the use of "VAP bundles". Oral decontamination, by reducing the microbial burden within a patient's oral cavity, is an essential part of VAP bundle strategy for reducing VAP rates in mechanically ventilated adults and older children. However there are no published studies of oral care products for VAP prevention in mechanically ventilated neonates. Biotene OralBalance® gel contains antibacterial active ingredients, including lactoperoxidase, lysozyme and lactoferrin,all enzymes with bacteriostatic or bactericidal activity on selective oral microflora. We hypothesize that by directly reducing the oral microbial burden, we indirectly reduce the number of VAP. This will be reflected in the reduced time on mechanical ventilation in the group of infants receiving Biotene OralBalance® gel.

This is a prospective, randomized, unmasked, controlled trial with 40 mechanically ventilated infants recruited from level IV nursery at Forsyth Medical Center, Winston-Salem, NC. The participants will be randomized to two equal groups, stratified by gestational age categories: <28 weeks, and >=28 weeks as well as multiple births. Twenty infants will receive Biotene OralBalance® gel (Intervention Group) and 20 infants will receive swabs with sterile water (Control Group) for timed oral care. Both study groups will receive the NICU standard ventilator-associated pneumonia (VAP) bundle, a combination of strategies aimed to reduce the rate of VAP.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Forsyth Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Brenner Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 week and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Neonates who are mechanically ventilated between 7 and 10 days old. Signed parental informed consent is required for recruitment into the study.

Exclusion Criteria:

• Neonates with chromosomal anomalies or major congenital anomalies, neonates with terminal conditions, neonates for whom a decision has been made not to provide full medical support, neonates whose parents refused or are unable to provide consent, and/or attending physician refusal.

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: Biotene OralBalance® gel Arm; Biotene OralBalance® gel contains antibacterial active ingredients: lactoperoxidase, lysozyme and lactoferrin. These enzymes occur naturally in the human milk and colostrum and have mimicking properties of the human saliva activity in vivo.	Drug: Biotene OralBalance® gel; Biotene OralBalance® gel is dispensed as 42gm, patient specific tube from hospital's Central Pharmacy. One pea-size oral application every 4 hours, or at touch time, to gums and tongue, as long as the subject remains mechanically ventilated for the duration of hospitalization.
Placebo Comparator: Sterile Water Arm; Sterile Water moisten cotton tipped applicator	Other: Sterile Water moisten cotton tipped applicator; One oral care application will be performed every 4 hours, or at touch times, to gums and tongue, as long as the subject remains mechanically ventilated for the duration of hospitalization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility	percentage of participants with retention	duration of study, for up to 30 months
Duration of Mechanical Ventilation	Time on invasive mechanical ventilation will be measured in days	3 days

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Investigators: Principal Investigator: Beatrice Stefanescu, MD, MS, Wake Forest University

Publications and helpful links

General Publications

• Tenovuo J. Clinical applications of antimicrobial host proteins lactoperoxidase, lysozyme and lactoferrin in xerostomia: efficacy and safety. Oral Dis. 2002 Jan;8(1):23-9. doi: 10.1034/j.1601-0825.2002.1o781.x.
• Tenovuo J, Lumikari M, Soukka T. Salivary lysozyme, lactoferrin and peroxidases: antibacterial effects on cariogenic bacteria and clinical applications in preventive dentistry. Proc Finn Dent Soc. 1991;87(2):197-208.
• Epstein JB, Emerton S, Le ND, Stevenson-Moore P. A double-blind crossover trial of Oral Balance gel and Biotene toothpaste versus placebo in patients with xerostomia following radiation therapy. Oral Oncol. 1999 Mar;35(2):132-7. doi: 10.1016/s1368-8375(98)00109-2.
• Apisarnthanarak A, Holzmann-Pazgal G, Hamvas A, Olsen MA, Fraser VJ. Ventilator-associated pneumonia in extremely preterm neonates in a neonatal intensive care unit: characteristics, risk factors, and outcomes. Pediatrics. 2003 Dec;112(6 Pt 1):1283-9. doi: 10.1542/peds.112.6.1283.
• Chlebicki MP, Safdar N. Topical chlorhexidine for prevention of ventilator-associated pneumonia: a meta-analysis. Crit Care Med. 2007 Feb;35(2):595-602. doi: 10.1097/01.CCM.0000253395.70708.AC.
• Stefanescu BM, Hetu C, Slaughter JC, O'Shea TM, Shetty AK. A pilot study of Biotene OralBalance(R) gel for oral care in mechanically ventilated preterm neonates. Contemp Clin Trials. 2013 Jul;35(2):33-9. doi: 10.1016/j.cct.2013.03.010. Epub 2013 Apr 20.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: March 9, 2011
• First Submitted That Met QC Criteria: March 11, 2011
• First Posted (Estimate): March 14, 2011

Study Record Updates

• Last Update Posted (Actual): September 11, 2018
• Last Update Submitted That Met QC Criteria: August 13, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: mechanical ventilation; feasibility; neonates; ventilator-associated pneumonia; oral care; duration of mechanical ventilation
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Cross Infection; Iatrogenic Disease; Healthcare-Associated Pneumonia; Pneumonia; Pneumonia, Ventilator-Associated
• Other Study ID Numbers: IRB00013036; FMC 2010-100 (Other Identifier: Forsyth Medical Center IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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