Pain Perception During Vulvar Biopsy

• Sponsor: Duke University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03654417
• Collaborator: (none)
• Enrollment: 37
• Location: 1
• Arms: 2
• Actual Duration (Months): 5.8
• Patients Per Site Per Month: 6.4

Study Details

Study Description

Brief Summary

The purpose of this study is to compare pain control during vulvar biopsy following either (1) application of EMLA (a eutectic mixture of local anesthetics lidocaine 2.5% and prilocaine 2.5%) cream or (2) injection of 1% lidocaine. We hypothesize that lidocaine will provide better biopsy analgesia, but the benefit will be offset by the pain of lidocaine injection compared to EMLA application, thus there will not be a significant difference in highest pain scores between the two groups.

Condition or Disease	Intervention/Treatment	Phase
Any Condition Requiring Vulvar Biopsy	Drug: EMLA; Drug: Lidocaine	Phase 4

Detailed Description

Performing minor procedures in-office is essential to gynecologic practices. In-office procedures allow for evaluation and diagnosis of a variety of conditions while avoiding the expense, anesthesia, and time associated with the operating room. Pain and discomfort are frequently associated with these procedures, and ensuring that the patient has the least amount of discomfort is a priority. Very painful or uncomfortable procedures could potentially discourage a patient from returning to clinic or receiving the follow up that they may need. Psychological, physiologic, and social factors influence a patient's experience of pain. Previous studies, though mostly related to first trimester abortion procedures in the office, indicate that the procedure type, anxiety, depression, and general anticipation of pain predict increased pain during in office gynecologic procedures (1-4). A review by Ireland et al., found that a multimodal approach that includes patient counseling with other techniques is most effective in achieving optimum pain control for procedures (5,6).

Vulvar biopsies are associated with significant discomfort, and some form of anesthesia is required. The current standard in our group is to inject local anesthesia prior to vulvar biopsy. However, the injection itself is associated with its own level of pain that is not insignificant, and for many, the anticipation of receiving an injection is anxiety provoking. The use of topical anesthesia in lieu of injection or as pre-injection analgesia is variable.

Several previous studies have examined the use of topical anesthetics in the place of or in addition to injected anesthesia. Drouault et al. compared EMLA cream alone to injected lidocaine alone for pain relief in vulvar biopsy and found that pain associated with administration of anesthesia was significantly less for EMLA cream, but better biopsy analgesia was obtained with injected anesthesia. The study considered combined pain scores for both groups for the overall procedure (anesthesia + biopsy), it comments that the combined scores were lower for the EMLA group but failed to reach statistical significance. The study ultimately concluded that EMLA is the less painful procedure to obtain anesthesia and that it can be used as an alternative to injection for biopsies of the genital mucosa (7). This prior study did not compare the highest pain score between groups. Consideration of the highest pain score allows us to assess whether the injection of lidocaine could result in causing more pain than the biopsy itself using EMLA cream alone for anesthesia. Further, the study did not assess the subjects' or the providers' perception of the tolerability and acceptability of performing the procedure using either method. This is an important factor in any in office procedure

EMLA cream is the most extensively studied topical anesthetic. It is FDA approved for use as a topical anesthetic on the genital mucous membranes for superficial, minor surgery. EMLA cream requires between 7-10 minutes of absorption time on the genital mucosa for analgesic effect, with variable duration of analgesia following, usually around 15-20 minutes (9). There is a highly variable absorption rate for EMLA cream depending on the characteristics of the epithelium upon which it is applied as well as the duration and surface area of cream applied. On hair-bearing non-mucosal surfaces it can require 60 minutes of application time to obtain analgesic affect (10). The vulvar area is unique in that it contains both mucosal and non-mucosal and hair-bearing surfaces; this could greatly affect the absorption of EMLA and therefore affect analgesia. For this reason, we will exclude from the study patients requiring vulvar biopsy on hair bearing portion of the vulva.

Several previous studies have examined the use of topical anesthetics in the place of or in addition to injected anesthesia. Drouault et al. compared EMLA cream to injected lidocaine as described above. The study found that pain associated with administration of anesthesia was significantly less for EMLA cream, but better biopsy analgesia was obtained with injected anesthesia. However, there were some limitations to this study also noted above, that we plan to expand and improve upon with the current study.

Zilbert and Lewandoswki studied pre-treatment with EMLA cream prior to anesthesia injection and found that pain was decreased by 50% in patients pretreated compared to placebo prior to lidocaine injection.

Van den Berg studied application of EMLA alone versus lidocaine injection alone in punch biopsies and electrocoagulation of genital warts in men. The study found that in the punch biopsy cohort that the total pain scores (application of EMLA + biopsy versus injection of lidocaine + biopsy) were less for the EMLA group than the injected lidocaine group and the difference was statistically significant (11).

With its FDA approval for use as a topical anesthetic on the genital mucous membranes for superficial, minor surgery, it can be considered a standard of care to use EMLA for anesthesia prior to biopsy as an alternative to injection of lidocaine (10)

As there are no studies that consider the subjects' or the providers' perception of the acceptability or the tolerability of the procedure, this will be novel data for vulvar biopsy. However, acceptability and tolerability have been assessed in other procedural settings, such as in office endoscopic procedures, in which BS-11, a validated 11 point scale, is used to assess pain, anxiety, acceptability, tolerability, and levels of other procedure related symptoms (12-13).

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A Comparison of Pain Perception Using Topical EMLA Cream Versus Lidocaine Injection for Vulvar Biopsy: a Randomized Controlled Trial
• Actual Study Start Date: Sep 17, 2018
• Actual Primary Completion Date: Mar 12, 2019
• Actual Study Completion Date: Mar 12, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: EMLA	Drug: Lidocaine; Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.
Active Comparator: Lidocaine	Drug: EMLA; Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.

Outcome Measures

Primary Outcome Measures

1. Highest Pain Score [no more than 5 minutes after numbing or 5 minutes after biopsy]

   The highest pain score recorded (at time of numbing or at time of biopsy) controlled for baseline pain title: Please slide the tab along the line below to indicate pain in the area of your vulva (external genitalia) during numbing OR biopsy min: 0 (no pain) max: 100 (worst pain imaginable)

Secondary Outcome Measures

1. Pain During Biopsy as Measured by a Pain Scale [No more than 5 minutes after receiving the biopsy]

   self-reported level of pain following the biopsy title: Please slide the tab along the line below to indicate pain in the area of your vulva (external genitalia) during biopsy min: 0 (no pain) max: 100 (worst pain imaginable)

2. Baseline Vulvar Pain [no more than 30 minutes prior to procedure]

   self-reported level of vulvar pain immediately prior to the start of the procedure title: Please slide the tab along the line below to indicate pain in the area of your vulva (external genitalia) during biopsy min: 0 (no pain) max: 100 (worst pain imaginable)

3. Anxiety Before the Procedure as Measured by an Anxiety Scale [No more than 30 minutes before the procedure]

   self-reported level of anxiety immediately prior to the start of the procedure title: Slide the tab along the line below to indicate how nervous you feel about the procedure you are about to have min: 0 (not nervous) max: 100 (very nervous)

4. Generalized Anxiety Disorder 7-item (GAD-7) Score for Baseline Anxiety [no more than 30 minutes before the procedure]

   Self-reported anxiety score meant to assess a patient's baseline level of anxiety. The score ranges from 0 (minimal anxiety) to 21 (severe anxiety).

5. Acceptance of the Procedure as Measured by a Satisfaction Scale [up to 30 minutes after the procedure]

   self-reported acceptance of the procedure meant to assess a patient's acceptability through a scale title: Please slide the tab along the line below to indicate, overall, how acceptable the procedure performed today was min: 0 (completely acceptable) max: 100 (not at all acceptable)

6. Tolerance of Procedure as Measured by a Satisfaction Scale [Up to 30 minutes after the procedure]

   self-reported tolerance of the procedure meant to assess a patient's tolerance through a scale Title: Please slide the tab along the line below to indicate, overall, how you would rate the experience of your biopsy procedure today Min: 0 (I could easily handle having this procedure again) Max: 100 (I could never have this procedure done again)

7. Provider's Opinion of Subject Tolerance as Measured by a Scale [Up to 30 minutes after the procedure]

   provider-reported measure of how well they believe the patient tolerated the procedure title: Overall, how well did the subject tolerate the procedure today? min: 0 (well tolerated) max: 100 (poorly tolerated)

8. Provider's Overall Satisfaction With the Procedure as Measured by a Scale [Up to 30 minutes after the procedure]

   provider-reported measure of how well they believe the procedure went title: Overall, how satisfied are you with the procedure performed today? min: 0 (completely satisfied) max: 100 (not at all satisfied)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 89 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Females above age 18 presenting to Duke Gynecology Oncology clinic for vulvar biopsy

• Able to provide informed consent in English and agree to the risks of the study

Exclusion Criteria:

• Not able to provide informed consent

• Vulvar biopsy on a hair bearing surface

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke Univeristy	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Duke University

Investigators

• Principal Investigator: Laura Havrilesky, MD, Duke University

Study Documents (Full-Text)

• Informed Consent Form - Nov 11, 2018
• Study Protocol - Sep 23, 2019
• Statistical Analysis Plan - Apr 4, 2019

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT03654417
• Other Study ID Numbers: Pro00094298
• First Posted: Aug 31, 2018
• Last Update Posted: Jan 18, 2020
• Last Verified: Jan 1, 2020

• 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 Duke University: vulvar biopsy
• Additional relevant MeSH terms: Lidocaine

Study Results

Participant Flow

Arm/Group Title	EMLA	Lidocaine
Arm/Group Description	Lidocaine: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.	EMLA: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.
Period Title: Overall Study
STARTED	19	18
COMPLETED	19	18
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	EMLA	Lidocaine	Total
Arm/Group Description	Lidocaine: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.	EMLA: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.	Total of all reporting groups
Overall Participants	19	18	37
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	60	58.5	60
Sex: Female, Male (Count of Participants)
Female	19 100%	18 100%	37 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 5.3%	0 0%	1 2.7%
Not Hispanic or Latino	18 94.7%	18 100%	36 97.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 36.8%	9 50%	16 43.2%
White	12 63.2%	9 50%	21 56.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Highest Pain Score
Description	The highest pain score recorded (at time of numbing or at time of biopsy) controlled for baseline pain title: Please slide the tab along the line below to indicate pain in the area of your vulva (external genitalia) during numbing OR biopsy min: 0 (no pain) max: 100 (worst pain imaginable)
Time Frame	no more than 5 minutes after numbing or 5 minutes after biopsy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EMLA	Lidocaine
Arm/Group Description	Lidocaine: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.	EMLA: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.
Measure Participants	19	18
Median (Inter-Quartile Range) [units on a scale (mm)]	20	56.5

2. Secondary Outcome

Title	Pain During Biopsy as Measured by a Pain Scale
Description	self-reported level of pain following the biopsy title: Please slide the tab along the line below to indicate pain in the area of your vulva (external genitalia) during biopsy min: 0 (no pain) max: 100 (worst pain imaginable)
Time Frame	No more than 5 minutes after receiving the biopsy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EMLA	Lidocaine
Arm/Group Description	Lidocaine: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.	EMLA: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.
Measure Participants	19	18
Median (Inter-Quartile Range) [units on a scale (mm)]	6	3

3. Secondary Outcome

Title	Baseline Vulvar Pain
Description	self-reported level of vulvar pain immediately prior to the start of the procedure title: Please slide the tab along the line below to indicate pain in the area of your vulva (external genitalia) during biopsy min: 0 (no pain) max: 100 (worst pain imaginable)
Time Frame	no more than 30 minutes prior to procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EMLA	Lidocaine
Arm/Group Description	Lidocaine: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.	EMLA: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.
Measure Participants	19	18
Median (Inter-Quartile Range) [units on a scale (mm)]	0.0	0.0

4. Secondary Outcome

Title	Anxiety Before the Procedure as Measured by an Anxiety Scale
Description	self-reported level of anxiety immediately prior to the start of the procedure title: Slide the tab along the line below to indicate how nervous you feel about the procedure you are about to have min: 0 (not nervous) max: 100 (very nervous)
Time Frame	No more than 30 minutes before the procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EMLA	Lidocaine
Arm/Group Description	Lidocaine: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.	EMLA: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.
Measure Participants	19	18
Median (Inter-Quartile Range) [units on a scale (mm)]	19	31.5

5. Secondary Outcome

Title	Generalized Anxiety Disorder 7-item (GAD-7) Score for Baseline Anxiety
Description	Self-reported anxiety score meant to assess a patient's baseline level of anxiety. The score ranges from 0 (minimal anxiety) to 21 (severe anxiety).
Time Frame	no more than 30 minutes before the procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EMLA	Lidocaine
Arm/Group Description	Lidocaine: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.	EMLA: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.
Measure Participants	19	18
Minimal Anxiety (0-4)	13 68.4%	11 61.1%
Mild Anxiety (5-9)	5 26.3%	5 27.8%
Moderate Anxiety (10-14)	0 0%	1 5.6%
Severe Anxiety (15-21)	1 5.3%	1 5.6%

6. Secondary Outcome

Title	Acceptance of the Procedure as Measured by a Satisfaction Scale
Description	self-reported acceptance of the procedure meant to assess a patient's acceptability through a scale title: Please slide the tab along the line below to indicate, overall, how acceptable the procedure performed today was min: 0 (completely acceptable) max: 100 (not at all acceptable)
Time Frame	up to 30 minutes after the procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EMLA	Lidocaine
Arm/Group Description	Lidocaine: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.	EMLA: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.
Measure Participants	19	18
Median (Inter-Quartile Range) [units on a scale (mm)]	0	10.5

7. Secondary Outcome

Title	Tolerance of Procedure as Measured by a Satisfaction Scale
Description	self-reported tolerance of the procedure meant to assess a patient's tolerance through a scale Title: Please slide the tab along the line below to indicate, overall, how you would rate the experience of your biopsy procedure today Min: 0 (I could easily handle having this procedure again) Max: 100 (I could never have this procedure done again)
Time Frame	Up to 30 minutes after the procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EMLA	Lidocaine
Arm/Group Description	Lidocaine: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.	EMLA: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.
Measure Participants	19	18
Median (Inter-Quartile Range) [units on a scale (mm)]	2	17

8. Secondary Outcome

Title	Provider's Opinion of Subject Tolerance as Measured by a Scale
Description	provider-reported measure of how well they believe the patient tolerated the procedure title: Overall, how well did the subject tolerate the procedure today? min: 0 (well tolerated) max: 100 (poorly tolerated)
Time Frame	Up to 30 minutes after the procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EMLA	Lidocaine
Arm/Group Description	Lidocaine: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.	EMLA: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.
Measure Participants	19	18
Median (Inter-Quartile Range) [units on a scale (mm)]	3	15

9. Secondary Outcome

Title	Provider's Overall Satisfaction With the Procedure as Measured by a Scale
Description	provider-reported measure of how well they believe the procedure went title: Overall, how satisfied are you with the procedure performed today? min: 0 (completely satisfied) max: 100 (not at all satisfied)
Time Frame	Up to 30 minutes after the procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EMLA	Lidocaine
Arm/Group Description	Lidocaine: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.	EMLA: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.
Measure Participants	19	18
Median (Inter-Quartile Range) [units on a scale (mm)]	3	9.5

10. Post-Hoc Outcome

Title	Possible Pathologic Changes Associated With EMLA Cream Application
Description	To address the concern that EMLA might induce pathologic changes that could result in altered diagnosis, pathologist independent from initial diagnostic read will re-evaluate tissue slides and look for the previously described EMLA induced pathologic changes (pallor, necrosis, spongiosis, basophilic granules, acantholysis, clefting, papillary dermal edema). Pathologist will be blinded to whether or not patient received EMLA cream for biopsy. They will provide a score for all specimens that will be used to analyse any pathologic differences between patients exposed to EMLA and those not exposed to EMLA.
Time Frame	retrospective

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Up to 30 minutes after the procedure
Arm/Group Title	EMLA		Lidocaine
Arm/Group Description	Lidocaine: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.		EMLA: Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.
All Cause Mortality
	EMLA		Lidocaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/18 (0%)
Serious Adverse Events
	EMLA		Lidocaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	EMLA		Lidocaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/18 (0%)

Limitations/Caveats

unblinded patients and providers, prior experience with vulvar biopsy may be biasing, pre-procedure anxiety may be biased because posed after randomization, no gold standard for pain assessment

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.