Adverse Effects
Conditions
Keywords
lidocaine, pre-medication, mammography, pain, safety
Brief summary
The purpose of this study is to test the hypothesis that one-time application of 4% lidocaine gel (TOPICAINE) on the skin of the breasts and chest wall as recommended for pre-medication to reduce discomfort during screening mammography does not result in adverse effects, electrocardiogram (EKG) changes, or systemically toxic plasma concentration of lidocaine or its principal metabolite, monoethylglycinexylidide (MEGX).
Interventions
DRUG4% lidocaine gel
1 ounce 4% lidocaine gel on skin of breasts and chest wall for 1 hour under occlusion, then removed with warm water
Sponsors
Mountain States Tumor and Medical Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
35 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 35 years and older * intact skin on breasts and chest wall
Exclusion criteria
* sensitivity or allergy to lidocaine * liver or kidney dysfunction * pregnant * breast feeding * currently smoke or chew tobacco * used lidocaine products within 48 hours of baseline lab, EKG, or gel application * exhibit neurological or cardiac signs or symptoms prior to gel application * are taking antiarrythmic medications, ciprofloxacin, erythromycin products, or oral contraceptives * history of Wolffe-Parkinson-White Syndrome (WPW) or congestive heart failure * heart rate below 60 or above 100 beats per minute * systolic blood pressure below 95 or above 180 mm Hg * PR interval greater 200 msec, QRS duration greater than 120 msec, QTc greater than 450 msec, or evidence of WPW on EKG * have an automatic implantable cardioverter defibrillator (AICD) or cardiac pacemaker * have had cancer, surgery, trauma, or myocardial infarction in the past 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameters Based on Plasma Concentration of Lidocaine and MEGX in Nanograms/Milliliter. | Prior to gel application, and at 30 min, 60 min, and 2, 3, 4, 6, and 8 hours after | Plasma concentration of lidocaine and MEGX in nanograms/milliliter were measured prior to one-time application of 4% lidocaine gel on the skin of the breasts and chest wall as recommended for use as as pre-medication to reduce discomfort during screening mammography, and at 30 minutes, 60 minutes, and 2, 3, 4, 6, and 8 hours. Due to the high frequency of nondetectable values, pharmacokinetic parameters could not be estimated. Measurements at all time points were grouped together to select a median. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| EKG Changes | Prior to gel application and 3 hours after | The PR interval (msec), QRS duration (msec), and QTc interval (msec) were compared between the baseline and subsequent EKG using paired t-tests. |
| Variation of Heart Rate (Bpm), Respiratory Rate (Respirations Per Minute, Rpm), Systolic Blood Pressure (mm Hg), and Diastolic Blood Pressure (mm Hg) Over Time. | Prior to gel application and at 30 min, 60 min and 2, 3, 4, 6. and 8 hours after | Variation of heart rate (bpm), respiratory rate (respirations per minute, rpm), systolic blood pressure (mm Hg), and diastolic blood pressure (mm Hg) over time was assessed using generalized linear mixed models with time modeled as a fixed effect and study subject modeled as a random effect. |
| Frequencies of Moderate, Severe, or Life-threatening Side Effects | Prior to gel application and at 30 min, 60 min and 2, 3, 4, 6. and 8 hours after | Percentages of study subjects exhibiting moderate, severe, or life-threatening signs and symptoms at each of the eight time measurements |
Countries
United States
Participant flow
Recruitment details
Recruitment fliers were posted at St. Luke's health System's oncology, screening mammography, internal medicine, and family health clinics, in-patient hospitals, and Boise State University.
Pre-assignment details
56 potential subjects responded to the fliers during the enrollment period. 31 did not meet study criteria. 13 enrolled. 3 did not meet the preliminary EKG or laboratory criteria and were withdrawn prior to gel application. 10 subjects completed the trial.
Participants by arm
| Arm | Count |
|---|---|
| Lidocaine Gel 1 ounce of lidocaine gel applied the skin of the breasts and chest wall covered by plastic wrap for one hour | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Failed preliminary EKG or lab criteria. | 3 |
Baseline characteristics
| Characteristic | Lidocaine Gel |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Age, Continuous | 53.9 years STANDARD_DEVIATION 9.8 |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Pharmacokinetic Parameters Based on Plasma Concentration of Lidocaine and MEGX in Nanograms/Milliliter.
Plasma concentration of lidocaine and MEGX in nanograms/milliliter were measured prior to one-time application of 4% lidocaine gel on the skin of the breasts and chest wall as recommended for use as as pre-medication to reduce discomfort during screening mammography, and at 30 minutes, 60 minutes, and 2, 3, 4, 6, and 8 hours. Due to the high frequency of nondetectable values, pharmacokinetic parameters could not be estimated. Measurements at all time points were grouped together to select a median.
Time frame: Prior to gel application, and at 30 min, 60 min, and 2, 3, 4, 6, and 8 hours after
Population: Plasma lidocaine and MEGX levels were measured prior to lidociane gel application, and at 30 min, 60, min, and 2, 3, 4, 6, and 8 hours after on 10 subjects (total of 80 lidocaine levels and 80 MEGX levels). Minimum level of detection for lidocaine and MEGX was 200 ng/mL.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lidocaine Gel Group | Pharmacokinetic Parameters Based on Plasma Concentration of Lidocaine and MEGX in Nanograms/Milliliter. | lidocaine | NA nanograms/mililiter |
| Lidocaine Gel Group | Pharmacokinetic Parameters Based on Plasma Concentration of Lidocaine and MEGX in Nanograms/Milliliter. | MEGX | NA nanograms/mililiter |
Comparison: Null Hypothesis: Application of 4% lidocaine gel on the breasts and chest wall of healthy women occluded for one hour does not result in systemically toxic plasma concentrations of lidocaine or its principal metabolite, monoethylglycinexyliidie (MEGX), electrocardiogram changes, or adverse events.p-value: <0.05non-compartmental pharmacokinetic
Secondary
EKG Changes
The PR interval (msec), QRS duration (msec), and QTc interval (msec) were compared between the baseline and subsequent EKG using paired t-tests.
Time frame: Prior to gel application and 3 hours after
Secondary
Frequencies of Moderate, Severe, or Life-threatening Side Effects
Percentages of study subjects exhibiting moderate, severe, or life-threatening signs and symptoms at each of the eight time measurements
Time frame: Prior to gel application and at 30 min, 60 min and 2, 3, 4, 6. and 8 hours after
Secondary
Variation of Heart Rate (Bpm), Respiratory Rate (Respirations Per Minute, Rpm), Systolic Blood Pressure (mm Hg), and Diastolic Blood Pressure (mm Hg) Over Time.
Variation of heart rate (bpm), respiratory rate (respirations per minute, rpm), systolic blood pressure (mm Hg), and diastolic blood pressure (mm Hg) over time was assessed using generalized linear mixed models with time modeled as a fixed effect and study subject modeled as a random effect.
Time frame: Prior to gel application and at 30 min, 60 min and 2, 3, 4, 6. and 8 hours after