title: Safety and Efficacy of a Needle-free Powder Lidocaine Delivery System in Pediatric Patients Undergoing Venipuncture or Peripheral Venous Cannulation: Randomized Double-blind COMFORT-004 Trial.
abstract: OBJECTIVE
  The goal of this study was to determine if a lidocaine hydrochloride monohydrate powder intradermal system designed to provide cutaneous analgesia is efficacious, safe, and tolerable for pediatric subjects compared with a sham placebo system.
  
  
  METHODS
  COMFORT-004, A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Confirm the Effectiveness and Safety of ALGRX 3268 in Pediatric Subjects, was a single-dose, parallel group study of children undergoing venipuncture or peripheral venous cannulation at the antecubital fossa or back of the hand. Included were subjects (3-18 years) in 3 age groups: 3-7, 8-12, and 13-18 years. Excluded were those with recent similar procedures or with implantable devices or skin pathologies at the anatomical site, insufficient cognitive skills, or allergies to local anesthetics or adhesives. Subjects were randomized to receive the needle-free powder lidocaine delivery system (active system, 0.5 mg of lidocaine/21 ± 1 bar of pressure [n = 269]) or sham placebo (n = 266) 1-3 minutes before venipuncture or peripheral venous cannulation. Analgesic efficacy was assessed patient self-report of venous access pain (Wong-Baker FACES Pain Rating Scale [3-18 years] and visual analog scale [VAS; 8-18 years]) and parental observational VAS. Safety assessments included adverse events (AEs) and relationship to study treatment. Skin signs and symptoms were graded numerically. Wong-Baker FACES scores, VAS, and parental VAS were analyzed by using an ANOVA model. Responder ratings and success rates were compared by using a Cochran-Mantel-Haenszel test stratified according to center, age group, and body site.
  
  
  RESULTS
  The active system group had significantly (P = 0.0022) less pain compared with the sham placebo in all age groups combined according to the modified Wong-Baker FACES scale. Secondary efficacy analyses found that the active system resulted in less pain as assessed by subjects' VAS pain assessments aged 8-18 years (P = 0.1856), responder analysis (P = 0.054), and parents' VAS assessments (P = 0.002). Venous procedures were successful in 95.5% and 96.2% of the active system and sham placebo groups, respectively. Treatment-emergent AEs, most commonly nausea and/or emesis, were not significant between groups. There were no serious AEs. The active system group had significantly more minor erythema and hemorrhage/petechiae.
  
  
  CONCLUSIONS
  The needle-free powder lidocaine delivery system was well tolerated and produced superior analgesia compared with sham placebo when administered 1-3 minutes before pediatric venipuncture or peripheral venous cannulation. Treatment-related AEs occurred primarily at the administration site and were infrequent, generally mild, and resolved without sequelae. ClinicalTrials.gov identifier: NCT00140088.
authors.affiliation: Arkansas Children׳s Hospital, Little Rock, Arkansas. Electronic address: schmitzmichaell@uams.edu.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Schmitz
authors.affiliation: Connecticut Children's Medical Center, Hartford, Connecticut.
authors.forename: William T
authors.initials: WT
authors.lastname: Zempsky
authors.affiliation: Marathon Pharmaceuticals, LLC, Northbrook, Illinois.
authors.forename: James M
authors.initials: JM
authors.lastname: Meyer
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000779:Anesthetics, Local / Q000008:administration & dosage*; D002406:Catheterization, Peripheral / Q000379:methods*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008012:Lidocaine / Q000008:administration & dosage*; D008297:Male; D009339:Needles; D010146:Pain / Q000517:prevention & control; D059408:Pain Management; D010147:Pain Measurement / Q000379:methods; D018962:Phlebotomy / Q000379:methods*; D011208:Powders
chemical_list: D000779:Anesthetics, Local; D011208:Powders; D008012:Lidocaine
keywords: adolescent; child; lidocaine; pain assessment; peripheral cannulation; transdermal administration; venipuncture