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

• ClinicalTrials.gov Identifier: NCT03562481
• Recruitment Status: Completed
• First Posted: June 19, 2018
• Results First Posted: June 25, 2020
• Last Update Posted: June 25, 2020
• Sponsor: University of North Carolina, Chapel Hill
• Information provided by (Responsible Party): University of North Carolina, Chapel Hill

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Anesthesia, Local; Pain	Drug: 1% Buffered Lidocaine 1:100,000 Epinephrine; Drug: 2% Unbuffered Lidocaine 1:100,000 Epinephrine	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment

Intervention Model Description

Study subjects will serve as their own controls in this crossover AB/BA study design which is uniform within sequences (groups, i.e. AB/BA, of order of drug formulation administration), uniform within periods (equal time between administration of alternating drug formulations), and balanced (equal number of subjects within each study arm).

The randomization will be performed to the type of drug given first, using a balanced randomization (half subjects buffered, half unbuffered) implemented with SAS software routines. During the first session, each subject will receive an IAN block with the first randomly assigned anesthetic formulation using the Halstead technique. At least a week later, substantially longer than the elimination half-life of the drug lidocaine (1.5-2hr), local anesthetic injections will be done using the alternate local anesthetic formulation.

• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Pilot Study: Comparison of Buffered 1% vs. Unbuffered 2% Lidocaine in Pediatric Subjects; Clinical Outcomes
• Actual Study Start Date: July 24, 2018
• Actual Primary Completion Date: June 30, 2019
• Actual Study Completion Date: June 30, 2019

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: Xylocaine

Outcome Measures

Primary Outcome Measures :

1. Mean Pain Scores Following Injection [ Time Frame: Within 10 minutes of 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.
2. Mean Time to Lower Lip Numbness Following Injection [ Time Frame: Up to 30 minutes following injection ]
   Time in minutes beginning immediately following injection to patient-reported lip numbness
3. Average Serum Lidocaine Concentration at 15 Minutes Post Injection [ Time Frame: One blood draw taken 15 minutes following 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).
4. Mean Time to Baseline Lip Sensation [ Time Frame: Within 24 hours following injection ]
   Response in minutes from injection to when lip is no longer numb, as self reported by patient.
5. Number of Participants Who Respond to Cold Stimulus (Positive/Negative) Prior to Injection [ Time Frame: 5 minutes prior to injection ]
   Response to experiencing sensation to cold stimulus on permanent molar tooth prior to injection
6. Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 30 Minutes Following Injection [ Time Frame: 30 minutes following injection ]
   Response to experiencing sensation to cold stimulus on permanent molar tooth 30 minutes following injection
7. Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 60 Minutes Following Injection [ Time Frame: 60 minutes following injection ]
   Response to experiencing sensation to cold stimulus on permanent molar tooth 60 minutes following injection
8. Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 90 Minutes Following Injection [ Time Frame: 90 minutes following injection ]
   Response to experiencing sensation to cold stimulus on permanent molar tooth 90 minutes following injection
9. Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 120 Minutes Following Injection [ Time Frame: 120 minutes following injection ]
   Response to experiencing sensation to cold stimulus on permanent molar tooth 120 minutes following injection

Eligibility Criteria

• Ages Eligible for Study: 10 Years to 12 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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)

Contacts and Locations

Locations

United States, North Carolina

UNC School of Dentistry

Chapel Hill, North Carolina, United States, 27599

Sponsors and Collaborators

University of North Carolina, Chapel Hill

Investigators

• Principal Investigator: Jessica Y Lee, DDS,MPH,PhD; UNC-Chapel Hill School of Dentistry, Pediatric Dentistry

  Study Documents (Full-Text)

Documents provided by University of North Carolina, Chapel Hill:

Study Protocol and Statistical Analysis Plan  [PDF] December 15, 2016

More Information

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT03562481
• Other Study ID Numbers: 16-3106
• First Posted: June 19, 2018
• Results First Posted: June 25, 2020
• Last Update Posted: June 25, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: 9 to 36 months following publication
• 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.

• 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

Keywords provided by University of North Carolina, Chapel Hill:

Healthy pediatric volunteers

Additional relevant MeSH terms:

Lidocaine; Epinephrine; Racepinephrine; Epinephryl borate; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Adrenergic beta-Agonists; Bronchodilator Agents; Autonomic Agents; Anti-Asthmatic Agents; Respiratory System Agents; Mydriatics; Sympathomimetics; Vasoconstrictor Agents