Clinical Trial Comparing Effectiveness of Buffered Versus... | NCT03562481

Status Module

Oversight Module

Description Module

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:

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

Null Hypotheses:

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.
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.

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Buffered Anesthetic, then Unbuffered Anesthetic	Experimental	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 Drug: 2% Unbuffered Lidocaine 1:100,000 Epinephrine
Unbuffered Anesthetic, then Buffered Anesthetic	Experimental	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 Drug: 2% Unbuffered Lidocaine 1:100,000 Epinephrine

Interventions

Name	Type	Description	Arm Group Labels	Other Names
1% Buffered Lidocaine 1:100,000 Epinephrine	Drug	A single IAN block with 3cc 1% Buffered Lidocaine (30mg) 1:100,000 Epinephrine using the Halstead technique.	Buffered Anesthetic, then Unbuffered Anesthetic

Outcomes Module

Primary Outcomes

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

Eligibility Module

Name	Affiliation	Role
Jessica Y Lee, DDS,MPH,PhD	UNC-Chapel Hill School of Dentistry, Pediatric Dentistry	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
UNC School of Dentistry		Chapel Hill	North Carolina	27599	United States

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Sequence 1: 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. 1% After one week minimum washout period, subjects will then receive an injection with Buffered Lidocaine 1:100,000 Epinephrine.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Dec 15, 2016

Arm/Group Information

ID	Title	Description
BG000	Sequence 1: 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.
BG001	Sequence 2: 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.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00012 BG00114 BG00226

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00011.5± 0.5 BG00110.9± 0.9 BG00211.2± 0.8

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0004 BG0019 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Asian	BG0001 BG0010 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00012 BG00114 BG002

Response to Cold Testing

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Negative Response to Cold Testing at Baseline	BG0002 BG0014 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

One participant did not complete the second intervention and was excluded from the data analysis.

Posted

Mean

Standard Deviation

score on a scale

Within 10 minutes of injection

ID	Title	Description
OG000	Buffered Anesthetic	Subjects being administered the Buffered Anesthetic received an injection with 3cc 1% Buffered Lidocaine 1:100,000 Epinephrine. for a single IAN block using the Halstead technique. 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.
OG001	Unbuffered Anesthetic	Subjects being administered the Unbuffered Anesthetic received an injection with 3cc of 2% Unbuffered Lidocaine with 1:100,000 Epinephrine for a single IAN block using the Halstead technique. 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.

Units	Counts
Participants	OG00025 OG00125

Title

Denominators

Categories

Title	Measurements
	OG0003.0± 1.9 OG0013.3± 1.5

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANOVA	Analysis of variance for a 2x2 crossover study implemented using the pkcross routine of Stata 16.1, accounting of sequence and period effects.	0.38	The threshold for statistical significance p<0.05	F statistic	0.80			2-Sided								Equivalence	Analysis of variance for a 2x2 crossover study implemented using the pkcross routine of Stata 16.1, accounting of sequence and period effects.

Primary

Mean Time to Lower Lip Numbness Following Injection

Time in minutes beginning immediately following injection to patient-reported lip numbness

One participant did not complete the second intervention and was excluded from the data analysis.

Posted

Mean

Standard Deviation

minutes

Up to 30 minutes following injection

ID	Title	Description
OG000	Buffered 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. 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.
OG001	Unbuffered 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. 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.

Primary

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 participant did not complete the second intervention and was excluded from the data analysis.

Posted

Mean

Standard Deviation

mcg/ml

One blood draw taken 15 minutes following injection

ID	Title	Description
OG000	Buffered 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. 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.
OG001	Unbuffered 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. 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.

Primary

Mean Time to Baseline Lip Sensation

Response in minutes from injection to when lip is no longer numb, as self reported by patient.

One participant did not complete the second intervention and was excluded from the data analysis.

Posted

Mean

Standard Deviation

minutes

Within 24 hours following injection

ID	Title	Description
OG000	Buffered 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. 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.
OG001	Unbuffered 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. 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.

Primary

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

One participant did not complete the second intervention and was excluded from the data analysis.

Posted

Count of Participants

Participants

5 minutes prior to injection

ID	Title	Description
OG000	Buffered Anesthetic	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.
OG001	Unbuffered Anesthetic	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.

Units	Counts
Participants	OG000

Primary

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

One participant did not complete the second intervention and was excluded from the data analysis.

Posted

Count of Participants

Participants

30 minutes following injection

ID	Title	Description
OG000	Buffered 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. 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.
OG001	Unbuffered 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. 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.

Primary

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

One participant did not complete the second intervention and was excluded from the data analysis.

Posted

Count of Participants

Participants

60 minutes following injection

ID	Title	Description
OG000	Buffered 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. 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.
OG001	Unbuffered 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. 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.

Primary

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

One participant did not complete the second intervention and was excluded from the data analysis.

Posted

Count of Participants

Participants

90 minutes following injection

ID	Title	Description
OG000	Buffered 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. 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.
OG001	Unbuffered 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. 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.

Primary

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

One participant did not complete the second intervention and was excluded from the data analysis.

Posted

Count of Participants

Participants

120 minutes following injection

ID	Title	Description
OG000	Buffered 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. 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.
OG001	Unbuffered 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. 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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Buffered Anesthetic	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.	0	25	0	25	0	25
EG001	Unbuffered Anesthetic	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.	0	26	0	26	0	26

Ancestor Terms

ID	Term
D004983	Ethanolamines
D000605	Amino Alcohols
D000438	Alcohols
D009930	Organic Chemicals
D000588	Amines
D015306	Biogenic Monoamines
D001679	Biogenic Amines
D002395	Catecholamines
D002396	Catechols
D010636	Phenols
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D000083	Acetanilides
D000813	Anilides
D000577	Amides
D000814	Aniline Compounds

ID	Term
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms