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Buffered Lidocaine for Loop Electrosurgical Excision Procedures (LEEPs)

Sponsor
Washington University School of Medicine (Other)
Overall Status
Completed
CT.gov ID
NCT01405768
Collaborator
(none)
56
Enrollment
1
Location
2
Arms
17.1
Duration (Months)
3.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Women undergoing a LEEP procedure who receive lidocaine buffered with sodium bicarbonate for their cervical block will experience less injection pain than women who receive plain lidocaine.

Condition or Disease Intervention/Treatment Phase
  • Drug: sodium bicarbonate buffered lidocaine
  • Drug: Non-buffered lidocaine
 Phase 2

Detailed Description

Specific aims:

  1. To determine whether buffering the agent used for intracervical anesthetic at the time of cervical loop excision reduces injection-related pain. (Hypothesis: buffering significantly reduces injection-related pain.)

  2. To determine whether other components of pain from LEEP (procedural pain, and cramping) can be reduced by buffering of intracervical anesthetic among women undergoing cervical loop excision. (Hypothesis: only injection pain will be reduced by buffering, as procedural pain will be reduced by lidocaine equally in both arms and cramping will not be reduced in either arm.)

Background:

Although cervical cancer rates have been dramatically reduced by Pap test screening and the eradication of precursors, more than 100,000 U.S. women develop premalignant cervical lesions each year that require treatment (1). The cervical loop electrosurgical excision procedure (LEEP) is the most common therapy for CIN among U.S. gynecologists. LEEP is performed using one or more 1-2 cm electrosurgical diathermy loops to excise involved and at-risk cervical epithelium including underlying stroma containing glands. Destroying this tissue eliminates cells infected with human papillomavirus, the proximate cause of cervical cancer, and radically reduces the risk of later developing cervical cancer (2, 3).

LEEP is usually performed as an outpatient procedure using intracervical anesthesia, most commonly combining lidocaine as an anesthetic agent with epinephrine as a hemostatic agent; final hemostasis is achieved using electrosurgical fulguration and topical hemostatic agents (4). Prior literature has suggested that pain from LEEP has 3 components: pain from injection of the anesthetic combination, pain from the excision, and cramping from reflex uterine contractions (5). While cramping can be controlled with oral nonsteroidal anti-inflammatory agents, injection and procedural pain are not. Most women categorize the pain of LEEP as 3-7 on a 0-10 Likert scale (5, 6).

Studies of dermal and ocular anesthesia and bone marrow biopsy have found that buffering of acidic local anesthetic agents reduces injection pain (7-14), with up to 66% reduction in pain and significant results in randomized trials involving 30-50 participants. However, the use of buffered lidocaine has not yet been tested for LEEPs. The principal investigator has used both forms of anesthesia and considers both acceptable forms of therapy; he is unaware of any evidence to support the superiority of either arm.

Study Design

Study Type:
Interventional
Actual Enrollment :
56 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Supportive Care
Official Title:
A Randomized Trial of Buffered vs Nonbuffered Lidocaine With Epinephrine for Cervical Loop Excision
Study Start Date :
Jul 1, 2011
Actual Primary Completion Date :
Oct 1, 2012
Actual Study Completion Date :
Dec 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Lidocaine Arm

Women in this arm will receive plain lidocaine with epinephrine injected into their cervix prior to the LEEP procedure.

Drug: Non-buffered lidocaine
Experimental: Buffered Lidocaine

Women in this arm will receive sodium bicarbonate buffered lidocaine mixed with epinephrine injected into their cervix prior to the LEEP procedure.

Drug: sodium bicarbonate buffered lidocaine
8.4% sodium bicarbonate will be mixed with lidocaine in a 1:10 ratio prior to mixing with epinephrine and injecting into the cervix.

Outcome Measures

Primary Outcome Measures

  1. Injection Pain Score (Mean) [Within 30 minutes of completion of procedure]

    A Likert visual analog scale will be used to document each study participant's level of pain experienced during injection of the cervical block. Within 30 minutes of completion of the procedure and after instruction by the investigators, women reported the intensity of their pain by marking single lines across 100-mm Likert visual analog scales. Scales did not include hashmarks or internal descriptors, as these have been shown to bias responses and diminish reliability. Patient marks on 100-mm Likert scale lines were measured, and a score was determined by the length marked off in millimeters. Patients who wrote "no pain" were considered to have marked 0 mm.

  2. Injection Pain Score (Median) [Within 30 minutes of completion of the procedure]

    A Likert visual analog scale will be used to document each study participant's level of pain experienced during injection of the cervical block. Within 30 minutes of completion of the procedure and after instruction by the investigators, women reported the intensity of their pain by marking single lines across 100-mm Likert visual analog scales. Scales did not include hashmarks or internal descriptors, as these have been shown to bias responses and diminish reliability. Patient marks on 100-mm Likert scale lines were measured, and a score was determined by the length marked off in millimeters. Patients who wrote "no pain" were considered to have marked 0 mm.

Secondary Outcome Measures

  1. Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Mean) [Within 30 minutes of completion of procedure]

    A Likert visual analog scale will be used to determine the overall pain experienced by each study participant including injection pain, procedural pain, and cramping. Within 30 minutes of completion of the procedure and after instruction by the investigators, women reported the intensity of their pain by marking single lines across 100-mm Likert visual analog scales. Scales did not include hashmarks or internal descriptors, as these have been shown to bias responses and diminish reliability. Patient marks on 100-mm Likert scale lines were measured, and a score was determined by the length marked off in millimeters. Patients who wrote "no pain" were considered to have marked 0 mm.

  2. Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Median) [Within 30 minutes of completion of procedure]

    A Likert visual analog scale will be used to determine the overall pain experienced by each study participant including injection pain, procedural pain, and cramping. Within 30 minutes of completion of the procedure and after instruction by the investigators, women reported the intensity of their pain by marking single lines across 100-mm Likert visual analog scales. Scales did not include hashmarks or internal descriptors, as these have been shown to bias responses and diminish reliability. Patient marks on 100-mm Likert scale lines were measured, and a score was determined by the length marked off in millimeters. Patients who wrote "no pain" were considered to have marked 0 mm.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • antecedent biopsy read as

  • cervical intraepithelial neoplasia (CIN) grade 2 or 3 or microinvasive cancer

  • adenocarcinoma in situ

  • persistent CIN 1

  • antecedent pap read as

  • high grade squamous intraepithelial lesion

  • atypical glandular cells

  • persistent low grade squamous intraepithelial lesion

Exclusion Criteria:

  • anatomy unsuitable for safe office loop excision based on operator judgement

  • inability to tolerate procedure under local anesthesia

  • pregnancy

  • age less than 18 years

  • inability to understand spoken or written English

  • refusal of consent

  • prisoner

  • mental incapacity

  • anticoagulant or antiplatelet therapy, or known bleeding diathesis

  • use of analgesics other than over the counter medications(OTC meds include NSAIDS or Tylenol) within 7 days of scheduled LEEP

Contacts and Locations

Locations

Site City State Country Postal Code
1 Washington University School of Medicine Saint Louis Missouri United States 63110

Sponsors and Collaborators

  • Washington University School of Medicine

Investigators

  • Principal Investigator: L. Stewart Massad, M.D., Washington University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

Responsible Party:
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01405768
Other Study ID Numbers:
  • 201104269
First Posted:
Jul 29, 2011
Last Update Posted:
Jul 28, 2014
Last Verified:
Jun 1, 2014
Additional relevant MeSH terms:
Uterine Cervical Dysplasia
Cervical Intraepithelial Neoplasia
Lidocaine

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Lidocaine Arm Buffered Lidocaine
Arm/Group Description Women in this arm will receive plain lidocaine with epinephrine injected into their cervix prior to the LEEP procedure. Women in this arm will receive sodium bicarbonate buffered lidocaine mixed with epinephrine injected into their cervix prior to the LEEP procedure. sodium bicarbonate buffered lidocaine: 8.4% sodium bicarbonate will be mixed with lidocaine in a 1:10 ratio prior to mixing with epinephrine and injecting into the cervix.
Period Title: Overall Study
STARTED 28 28
COMPLETED 24 28
NOT COMPLETED 4 0

Baseline Characteristics

Arm/Group Title Lidocaine Arm Buffered Lidocaine Total
Arm/Group Description Women in this arm will receive plain lidocaine with epinephrine injected into their cervix prior to the LEEP procedure. Women in this arm will receive sodium bicarbonate buffered lidocaine mixed with epinephrine injected into their cervix prior to the LEEP procedure. sodium bicarbonate buffered lidocaine: 8.4% sodium bicarbonate will be mixed with lidocaine in a 1:10 ratio prior to mixing with epinephrine and injecting into the cervix. Total of all reporting groups
Overall Participants 24 28 52
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
Between 18 and 65 years
24
100%
28
100%
52
100%
>=65 years
0
0%
0
0%
0
0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
32.4
(10.3)
32.3
(7.6)
32.4
(9.2)
Sex: Female, Male (Count of Participants)
Female
24
100%
28
100%
52
100%
Male
0
0%
0
0%
0
0%
Race/Ethnicity, Customized (participants) [Number]
African American
13
54.2%
12
42.9%
25
48.1%
White
10
41.7%
14
50%
24
46.2%
Hispanic/Latina
0
0%
1
3.6%
1
1.9%
Other
1
4.2%
1
3.6%
2
3.8%
Region of Enrollment (participants) [Number]
United States
24
100%
28
100%
52
100%
Parity (participants) [Number]
0
3
12.5%
6
21.4%
9
17.3%
1
5
20.8%
7
25%
12
23.1%
2+
16
66.7%
15
53.6%
31
59.6%
Indication (participants) [Number]
HSIL
8
33.3%
4
14.3%
12
23.1%
CIN 2
4
16.7%
7
25%
11
21.2%
CIN 3
11
45.8%
15
53.6%
26
50%
AIS
1
4.2%
1
3.6%
2
3.8%
Persistent CIN 1
0
0%
1
3.6%
1
1.9%
Procedure type (participants) [Number]
Ectocervix only
16
66.7%
17
60.7%
33
63.5%
Ectocervix and endocervix
8
33.3%
11
39.3%
19
36.5%
Number of passes (participants) [Number]
1
6
25%
11
39.3%
17
32.7%
2
12
50%
12
42.9%
24
46.2%
3+
6
25%
5
17.9%
11
21.2%
Ectocervical loop size (in mm) (participants) [Number]
15 x 12
3
12.5%
7
25%
10
19.2%
20 x 12
13
54.2%
16
57.1%
29
55.8%
Other
8
33.3%
5
17.9%
13
25%
Endocervical loop size (in mm) (participants) [Number]
10 x 10
5
20.8%
11
39.3%
16
30.8%
15 x 12
2
8.3%
0
0%
2
3.8%
10 x 8
1
4.2%
0
0%
1
1.9%
Estimated blood loss (in mL) (participants) [Number]
0 mL
3
12.5%
6
21.4%
9
17.3%
1-5 mL
9
37.5%
8
28.6%
17
32.7%
6-10 mL
7
29.2%
9
32.1%
16
30.8%
>10 mL
5
20.8%
5
17.9%
10
19.2%
Anesthetic volume (in mL) (participants) [Number]
6-9 mL
12
50%
11
39.3%
23
44.2%
10 mL
11
45.8%
15
53.6%
26
50%
>10 mL
1
4.2%
2
7.1%
3
5.8%

Outcome Measures

1. Primary Outcome
Title Injection Pain Score (Mean)
Description A Likert visual analog scale will be used to document each study participant's level of pain experienced during injection of the cervical block. Within 30 minutes of completion of the procedure and after instruction by the investigators, women reported the intensity of their pain by marking single lines across 100-mm Likert visual analog scales. Scales did not include hashmarks or internal descriptors, as these have been shown to bias responses and diminish reliability. Patient marks on 100-mm Likert scale lines were measured, and a score was determined by the length marked off in millimeters. Patients who wrote "no pain" were considered to have marked 0 mm.
Time Frame Within 30 minutes of completion of procedure

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Lidocaine Arm Buffered Lidocaine
Arm/Group Description Women in this arm will receive plain lidocaine with epinephrine injected into their cervix prior to the LEEP procedure. Women in this arm will receive sodium bicarbonate buffered lidocaine mixed with epinephrine injected into their cervix prior to the LEEP procedure. sodium bicarbonate buffered lidocaine: 8.4% sodium bicarbonate will be mixed with lidocaine in a 1:10 ratio prior to mixing with epinephrine and injecting into the cervix.
Measure Participants 24 28
Mean (Standard Deviation) [units on a scale]
25
(19)
19
(17)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lidocaine Arm, Buffered Lidocaine
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value .13
Comments
Method Wilcoxon (Mann-Whitney)
Comments
2. Secondary Outcome
Title Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Mean)
Description A Likert visual analog scale will be used to determine the overall pain experienced by each study participant including injection pain, procedural pain, and cramping. Within 30 minutes of completion of the procedure and after instruction by the investigators, women reported the intensity of their pain by marking single lines across 100-mm Likert visual analog scales. Scales did not include hashmarks or internal descriptors, as these have been shown to bias responses and diminish reliability. Patient marks on 100-mm Likert scale lines were measured, and a score was determined by the length marked off in millimeters. Patients who wrote "no pain" were considered to have marked 0 mm.
Time Frame Within 30 minutes of completion of procedure

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Lidocaine Arm Buffered Lidocaine
Arm/Group Description Women in this arm will receive plain lidocaine with epinephrine injected into their cervix prior to the LEEP procedure. Women in this arm will receive sodium bicarbonate buffered lidocaine mixed with epinephrine injected into their cervix prior to the LEEP procedure. sodium bicarbonate buffered lidocaine: 8.4% sodium bicarbonate will be mixed with lidocaine in a 1:10 ratio prior to mixing with epinephrine and injecting into the cervix.
Measure Participants 24 28
Injection pain
25
(19)
19
(17)
Procedure pain
27
(18)
19
(17)
Cramping pain
19
(16)
18
(16)
3. Primary Outcome
Title Injection Pain Score (Median)
Description A Likert visual analog scale will be used to document each study participant's level of pain experienced during injection of the cervical block. Within 30 minutes of completion of the procedure and after instruction by the investigators, women reported the intensity of their pain by marking single lines across 100-mm Likert visual analog scales. Scales did not include hashmarks or internal descriptors, as these have been shown to bias responses and diminish reliability. Patient marks on 100-mm Likert scale lines were measured, and a score was determined by the length marked off in millimeters. Patients who wrote "no pain" were considered to have marked 0 mm.
Time Frame Within 30 minutes of completion of the procedure

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Lidocaine Arm Buffered Lidocaine
Arm/Group Description Women in this arm will receive plain lidocaine with epinephrine injected into their cervix prior to the LEEP procedure. Women in this arm will receive sodium bicarbonate buffered lidocaine mixed with epinephrine injected into their cervix prior to the LEEP procedure. sodium bicarbonate buffered lidocaine: 8.4% sodium bicarbonate will be mixed with lidocaine in a 1:10 ratio prior to mixing with epinephrine and injecting into the cervix.
Measure Participants 24 28
Median (Full Range) [units on a scale]
26
18
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lidocaine Arm, Buffered Lidocaine
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value .13
Comments
Method Wilcoxon (Mann-Whitney)
Comments
4. Secondary Outcome
Title Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Median)
Description A Likert visual analog scale will be used to determine the overall pain experienced by each study participant including injection pain, procedural pain, and cramping. Within 30 minutes of completion of the procedure and after instruction by the investigators, women reported the intensity of their pain by marking single lines across 100-mm Likert visual analog scales. Scales did not include hashmarks or internal descriptors, as these have been shown to bias responses and diminish reliability. Patient marks on 100-mm Likert scale lines were measured, and a score was determined by the length marked off in millimeters. Patients who wrote "no pain" were considered to have marked 0 mm.
Time Frame Within 30 minutes of completion of procedure

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Lidocaine Arm Buffered Lidocaine
Arm/Group Description Women in this arm will receive plain lidocaine with epinephrine injected into their cervix prior to the LEEP procedure. Women in this arm will receive sodium bicarbonate buffered lidocaine mixed with epinephrine injected into their cervix prior to the LEEP procedure. sodium bicarbonate buffered lidocaine: 8.4% sodium bicarbonate will be mixed with lidocaine in a 1:10 ratio prior to mixing with epinephrine and injecting into the cervix.
Measure Participants 24 28
Injection pain
26
18
Procedure pain
25
13
Cramping pain
19
14

Adverse Events

Time Frame Start of procedures through 30 days after completion of procedure. The procedure occurs on Day 1.
Adverse Event Reporting Description
Arm/Group Title Lidocaine Arm Buffered Lidocaine
Arm/Group Description Women in this arm will receive plain lidocaine with epinephrine injected into their cervix prior to the LEEP procedure. Women in this arm will receive sodium bicarbonate buffered lidocaine mixed with epinephrine injected into their cervix prior to the LEEP procedure. sodium bicarbonate buffered lidocaine: 8.4% sodium bicarbonate will be mixed with lidocaine in a 1:10 ratio prior to mixing with epinephrine and injecting into the cervix.
All Cause Mortality
Lidocaine Arm Buffered Lidocaine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN)
Serious Adverse Events
Lidocaine Arm Buffered Lidocaine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/28 (0%) 0/28 (0%)
Other (Not Including Serious) Adverse Events
Lidocaine Arm Buffered Lidocaine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/28 (0%) 0/28 (0%)

Limitations/Caveats

Small sample - may have missed a significant difference when one really exists Procedures performed by 2nd year residents vs. procedure performed by more skilled surgeon (less pain) Used needle extenders/27-gauge needles vs. Potocki needles

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.

Results Point of Contact

Name/Title L. Stewart Massad, M.D.
Organization Washington University School of Medicine
Phone 314-362-3181
Email massadl@wudosis.wustl.edu
Responsible Party:
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01405768
Other Study ID Numbers:
  • 201104269
First Posted:
Jul 29, 2011
Last Update Posted:
Jul 28, 2014
Last Verified:
Jun 1, 2014