Uterine Cervical DysplasiaPhase 2NCT01405768
Buffered Lidocaine for Loop Electrosurgical Excision Procedures (LEEPs)
A Phase 2 study testing sodium bicarbonate buffered lidocaine and Non-buffered lidocaine in people with Uterine Cervical Dysplasia, run by Washington University School of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Uterine Cervical Dysplasia
- What is being tested?
- sodium bicarbonate buffered lidocaine and Non-buffered lidocaine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2011to Dec 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Randomized Trial of Buffered vs Nonbuffered Lidocaine With Epinephrine for Cervical Loop Excision
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.
Read the detailed description
Specific aims:
- 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.)
- 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.
- Conditions
- Uterine Cervical Dysplasia
- Being tested
- sodium bicarbonate buffered lidocaine, Non-buffered lidocaine
- Medical subject headings
- Uterine Cervical Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sodium bicarbonate buffered lidocaineDrug
8.4% sodium bicarbonate will be mixed with lidocaine in a 1:10 ratio prior to mixing with epinephrine and injecting into the cervix.
Non-buffered lidocaineDrug
| Study group | Role | What they receive |
|---|---|---|
| Lidocaine Arm | Active comparator | Women in this arm will receive plain lidocaine with epinephrine injected into their cervix prior to the LEEP procedure. Receives: Drug: Non-buffered lidocaine |
| Buffered Lidocaine | Experimental | Women in this arm will receive sodium bicarbonate buffered lidocaine mixed with epinephrine injected into their cervix prior to the LEEP procedure. Receives: Drug: sodium bicarbonate buffered lidocaine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Injection Pain Score (Mean)
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.
Measured: Within 30 minutes of completion of procedure
Injection Pain Score (Median)
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.
Measured: Within 30 minutes of completion of the procedure
Secondary outcomes (2)
Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Mean)
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.
Measured: Within 30 minutes of completion of procedure
Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Median)
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.
Measured: Within 30 minutes of completion of procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2011 (estimated)
- Study startJul 2011
- Primary completionOct 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Uterine Cervical DysplasiaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- L. Stewart Massad, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01405768
- Sponsor's protocol ID
- 201104269
- Status last verified
- Jun 2014
- First submitted
- 28 Jul 2011
- Last updated
- 28 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Ruegg TA, Curran CR, Lamb T. Use of buffered lidocaine in bone marrow biopsies: a randomized, controlled trial. Oncol Nurs Forum. 2009 Jan;36(1):52-60. doi: 10.1188/09.ONF.52-60.
PubMed 19136338Sharma T, Gopal L, Shanmugam MP, Bhende P, George J, Samanta TK, Mukesh BN. Comparison of pH-adjusted bupivacaine with a mixture of non-pH-adjusted bupivacaine and lignocaine in primary vitreoretinal surgery. Retina. 2002 Apr;22(2):202-7. doi: 10.1097/00006982-200204000-00011.
PubMed 11927854Fitton AR, Ragbir M, Milling MA. The use of pH adjusted lignocaine in controlling operative pain in the day surgery unit: a prospective, randomised trial. Br J Plast Surg. 1996 Sep;49(6):404-8. doi: 10.1016/s0007-1226(96)90011-9.
PubMed 8881789Burns CA, Ferris G, Feng C, Cooper JZ, Brown MD. Decreasing the pain of local anesthesia: a prospective, double-blind comparison of buffered, premixed 1% lidocaine with epinephrine versus 1% lidocaine freshly mixed with epinephrine. J Am Acad Dermatol. 2006 Jan;54(1):128-31. doi: 10.1016/j.jaad.2005.06.043.
PubMed 16384767Younis I, Bhutiani RP. Taking the 'ouch' out - effect of buffering commercial xylocaine on infiltration and procedure pain - a prospective, randomised, double-blind, controlled trial. Ann R Coll Surg Engl. 2004 May;86(3):213-7. doi: 10.1308/003588404323043382.
PubMed 15140310Masters JE. Randomised control trial of pH buffered lignocaine with adrenaline in outpatient operations. Br J Plast Surg. 1998 Jul;51(5):385-7. doi: 10.1054/bjps.1997.0293.
PubMed 9771366Orlinsky M, Hudson C, Chan L, Deslauriers R. Pain comparison of unbuffered versus buffered lidocaine in local wound infiltration. J Emerg Med. 1992 Jul-Aug;10(4):411-5. doi: 10.1016/0736-4679(92)90269-y.
PubMed 1430977
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial of Buffered vs Nonbuffered Lidocaine With Epinephrine for Cervical Loop Excision
- ClinicalTrials.gov ID
- NCT01405768
- Acronym / sponsor ID
- 201104269
- Conditions
- Uterine Cervical Dysplasia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Jul 2011
- Primary completion
- Oct 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 29 Jul 2011 (estimated)
- Results
- Posted 28 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Specific aims:
- 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.)
- 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
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lidocaine Arm | Active comparator | Drug: Non-buffered lidocaineWomen in this arm will receive plain lidocaine with epinephrine injected into their cervix prior to the LEEP procedure. |
| Buffered Lidocaine | Experimental | Drug: sodium bicarbonate buffered lidocaineWomen in this arm will receive sodium bicarbonate buffered lidocaine mixed with epinephrine injected into their cervix prior to the LEEP procedure. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- antecedent biopsy read as
- antecedent pap read as
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sodium bicarbonate buffered lidocaine8.4% sodium bicarbonate will be mixed with lidocaine in a 1:10 ratio prior to mixing with epinephrine and injecting into the cervix. | Drug | Buffered Lidocaine |
| Non-buffered lidocaine | Drug | Lidocaine Arm |
Primary outcome
Injection Pain Score (Mean)
Time frame: 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.
Injection Pain Score (Median)
Time frame: 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.
2 secondary outcomes
Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Mean)
Time frame: Within 30 minutes of completion of procedure
Overall LEEP Procedure Pain Including Procedural Pain and Cramping (Median)
Time frame: Within 30 minutes of completion of procedure
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19136338Ruegg TA, Curran CR, Lamb T. Use of buffered lidocaine in bone marrow biopsies: a randomized, controlled trial. Oncol Nurs Forum. 2009 Jan;36(1):52-60. doi: 10.1188/09.ONF.52-60.
- Background: PubMed 11927854Sharma T, Gopal L, Shanmugam MP, Bhende P, George J, Samanta TK, Mukesh BN. Comparison of pH-adjusted bupivacaine with a mixture of non-pH-adjusted bupivacaine and lignocaine in primary vitreoretinal surgery. Retina. 2002 Apr;22(2):202-7. doi: 10.1097/00006982-200204000-00011.
- Background: PubMed 8881789Fitton AR, Ragbir M, Milling MA. The use of pH adjusted lignocaine in controlling operative pain in the day surgery unit: a prospective, randomised trial. Br J Plast Surg. 1996 Sep;49(6):404-8. doi: 10.1016/s0007-1226(96)90011-9.
- Background: PubMed 16384767Burns CA, Ferris G, Feng C, Cooper JZ, Brown MD. Decreasing the pain of local anesthesia: a prospective, double-blind comparison of buffered, premixed 1% lidocaine with epinephrine versus 1% lidocaine freshly mixed with epinephrine. J Am Acad Dermatol. 2006 Jan;54(1):128-31. doi: 10.1016/j.jaad.2005.06.043.
- Background: PubMed 15140310Younis I, Bhutiani RP. Taking the 'ouch' out - effect of buffering commercial xylocaine on infiltration and procedure pain - a prospective, randomised, double-blind, controlled trial. Ann R Coll Surg Engl. 2004 May;86(3):213-7. doi: 10.1308/003588404323043382.
- Background: PubMed 9771366Masters JE. Randomised control trial of pH buffered lignocaine with adrenaline in outpatient operations. Br J Plast Surg. 1998 Jul;51(5):385-7. doi: 10.1054/bjps.1997.0293.
- Background: PubMed 1430977Orlinsky M, Hudson C, Chan L, Deslauriers R. Pain comparison of unbuffered versus buffered lidocaine in local wound infiltration. J Emerg Med. 1992 Jul-Aug;10(4):411-5. doi: 10.1016/0736-4679(92)90269-y.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
L. Stewart Massad, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing sodium bicarbonate buffered lidocaine and Non-buffered lidocaine in people with Uterine Cervical Dysplasia, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Injection Pain Score (Mean) (time frame: Within 30 minutes of completion of procedure). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01405768, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2014.