Clinical Trial Comparing Effectiveness of Buffered Versus Unbuffered Local Anesthetic in Children Ages 10-12 Years

Pilot Study: Comparison of Buffered 1% vs. Unbuffered 2% Lidocaine in Pediatric Subjects; Clinical Outcomes

Local anesthesia is an integral part of clinical pediatric dental practice, but it has challenges. It can be uncomfortable for children, and the risk of adverse events limits how much is used. Some evidence suggests benefits of buffering local anesthetics including equal effect with less pain on injection. These findings have not been replicated and validated among pediatric populations, creating a gap in the knowledge base. To address this knowledge gap and contribute to the evidence base on safety and efficacy of local anesthesia in pediatric dentistry, this investigation proposes to compare the anesthetic effects of buffered 1% lidocaine with those of unbuffered 2%, among children.

The specific aims of this investigation are to determine differences between buffered 1% and unbuffered 2% lidocaine (both with 1:100,000 epinephrine) used for inferior alveolar nerve block (IAN) anesthesia, in the following domains:

1. Pain experience on injection, time to onset following the administration, and time to recovery [subjective]
2. Blood lidocaine levels 15 minutes following the administration and duration of pulpal anesthesia [objective]

Null Hypotheses:

1. No difference exists in anesthetic effectiveness for pulpal anesthesia after intraoral IAN block between buffered 1% Lidocaine with 1:100,000 epinephrine as compared to unbuffered 2% Lidocaine with 1:100,000 epinephrine.
2. No differences exist in peak blood lidocaine levels, pain on injection, time to lip numbness, and duration of anesthesia between the two drug formulations.

Randomized subjects will be injected orally for bottom jaw anesthesia, with 3cc of buffered 1% lidocaine (30mg) 1:100,000 epinephrine or 3cc unbuffered of 2% lidocaine (60mg) 1:100,000 epinephrine. The injectable volume of the buffered formulation will include 0.3cc of 8.4% sodium bicarbonate.

One faculty member in the Department of Pediatric Dentistry at the University of North Carolina (UNC) School of Dentistry will administer the drugs in the Pediatric Dentistry clinic. The same clinician will administer injection to the same subjects at both visits. Clinicians and subjects will not know which drug formulation is given at which appointment.

A clinician will measure the level of discomfort on injection, how long it takes for the lip to be numb, how long it takes for the first molar tooth in that area to be numb, how long it takes the local anesthetic to wear off, and how much of the anesthetic is in the blood.

Study Overview

• Status: Completed
• Conditions: Pain; Anesthesia, Local
• Intervention / Treatment: Drug: 1% Buffered Lidocaine 1:100,000 Epinephrine; Drug: 2% Unbuffered Lidocaine 1:100,000 Epinephrine

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC School of Dentistry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 10-12 years
• American Society of Anesthesiologists (ASA) Class I (Healthy)
• Body Weight: the Interquartile Range (IQR) 33-60Kg for subject ages
• Have ability to speak and read English
• Willingness to participate in two sessions
• No history of adverse reaction to dental anesthetic
• Have bilateral, disease/symptom-free mandibular first molars present

Exclusion Criteria:

• Allergy to lidocaine class of anesthetic drugs
• Local anesthetic drug use in past week
• Current symptomatic teeth or oral mucosa
• ASA II or above (including asthma)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Buffered Anesthetic, then Unbuffered Anesthetic; Subjects randomized to Buffered Anesthetic, then Unbuffered Anesthetic will first receive an injection with 1% Buffered Lidocaine 1:100,000 Epinephrine. After one week minimum washout period, subjects will then receive an injection with 2% Unbuffered Lidocaine 1:100,000 Epinephrine.	Drug: 1% Buffered Lidocaine 1:100,000 Epinephrine; A single IAN block with 3cc 1% Buffered Lidocaine (30mg) 1:100,000 Epinephrine using the Halstead technique.; Other Names: Xylocaine; Drug: 2% Unbuffered Lidocaine 1:100,000 Epinephrine; A single IAN block with 3cc 2% Unbuffered Lidocaine (60mg) 1:100,000 Epinephrine using the Halstead technique.; Other Names: Xylocaine
Experimental: Unbuffered Anesthetic, then Buffered Anesthetic; Subjects randomized to Unbuffered Anesthetic, then Buffered Anesthetic will first receive an injection with 2% Unbuffered Lidocaine 1:100,000 Epinephrine. After one week minimum washout period, subjects will then receive an injection with 1% Buffered Lidocaine 1:100,000 Epinephrine.	Drug: 1% Buffered Lidocaine 1:100,000 Epinephrine; A single IAN block with 3cc 1% Buffered Lidocaine (30mg) 1:100,000 Epinephrine using the Halstead technique.; Other Names: Xylocaine; Drug: 2% Unbuffered Lidocaine 1:100,000 Epinephrine; A single IAN block with 3cc 2% Unbuffered Lidocaine (60mg) 1:100,000 Epinephrine using the Halstead technique.; Other Names: Xylocaine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Pain Scores Following Injection	Perceived pain on injection, self-reported verbally using a Likert scale from 1-10, with lower numbers corresponding to less pain (1 = "no pain," 10 = "worst pain imaginable"). Lower scores reflect a lesser degree of pain.	Within 10 minutes of injection
Mean Time to Lower Lip Numbness Following Injection	Time in minutes beginning immediately following injection to patient-reported lip numbness	Up to 30 minutes following injection
Average Serum Lidocaine Concentration at 15 Minutes Post Injection	Blood Lidocaine Level (mcg/mL) as measured in 10cc venous blood, taken 15 minutes following injection. Blood assayed for serum lidocaine levels with a Sciex TripleTOF liquid chromatography- mass spectrometry (LC-MS) equipped with a C18 Hypersil (10mm x 2.1mm, 3.0μm).	One blood draw taken 15 minutes following injection
Mean Time to Baseline Lip Sensation	Response in minutes from injection to when lip is no longer numb, as self reported by patient.	Within 24 hours following injection
Number of Participants Who Respond to Cold Stimulus (Positive/Negative) Prior to Injection	Response to experiencing sensation to cold stimulus on permanent molar tooth prior to injection	5 minutes prior to injection
Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 30 Minutes Following Injection	Response to experiencing sensation to cold stimulus on permanent molar tooth 30 minutes following injection	30 minutes following injection
Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 60 Minutes Following Injection	Response to experiencing sensation to cold stimulus on permanent molar tooth 60 minutes following injection	60 minutes following injection
Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 90 Minutes Following Injection	Response to experiencing sensation to cold stimulus on permanent molar tooth 90 minutes following injection	90 minutes following injection
Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 120 Minutes Following Injection	Response to experiencing sensation to cold stimulus on permanent molar tooth 120 minutes following injection	120 minutes following injection

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Investigators: Principal Investigator: Jessica Y Lee, DDS,MPH,PhD, UNC-Chapel Hill School of Dentistry, Pediatric Dentistry

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2018
• Primary Completion (Actual): June 30, 2019
• Study Completion (Actual): June 30, 2019

Study Registration Dates

• First Submitted: June 5, 2018
• First Submitted That Met QC Criteria: June 18, 2018
• First Posted (Actual): June 19, 2018

Study Record Updates

• Last Update Posted (Actual): June 25, 2020
• Last Update Submitted That Met QC Criteria: June 4, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Healthy pediatric volunteers
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Adrenergic alpha-Agonists; Adrenergic Agonists; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Lidocaine; Epinephrine; Racepinephrine; Epinephryl borate
• Other Study ID Numbers: 16-3106

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB) and executes a data use/sharing agreement with UNC.
• IPD Sharing Time Frame: 9 to 36 months following publication
• IPD Sharing Access Criteria: Investigators who propose to use the data must have approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB) and must execute a data use/sharing agreement with UNC.
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes