Lessons on Urethral Lidocaine in Urodynamics (LULU): Impact of Intraurethral Lidocaine on Cystometric Parameters and Discomfort
Phase: PHASE4
Conditions: Urethra Issue, Pelvic Organ Prolapse, Urinary Incontinence, Vaginal Vault Prolapse, Cystocele, Uterine Prolapse, Vaginal Prolapse, Pelvic Floor Disorders
Sponsor: University of Texas Southwestern Medical Center

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Lessons on Urethral Lidocaine in Urodynamics (“LULU”): Impact of intraurethral
lidocaine on cystometric parameters and discomfort, a RCT
NCT04038099
11/22/2019

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Lessons on Urethral Lidocaine in Urodynamics (“LULU”): Impact of intraurethral
lidocaine on cystometric parameters and discomfort, a RCT
Abstract
Complex cystometric studies are often conducted to assess for and clarify incontinence.
In current practice, intraurethral aqueous jelly is used to lubricate and insert urethral catheters
for these studies.  Patients commonly complain of urethral discomfort and/or pain with catheter
insertion.  Two percent lidocaine jelly has not been routinely used in practice for cystometric
catheter insertion due to the unknown impact it may or may not have on complex cystometric
parameters.  Previous studies evaluating the use of 2% lidocaine jelly for office cystoscopy have
not proven to consistently provide substantial relief of discomfort.  However, a recent study
using 2% lidocaine jelly for catheter insertion during complex cystometric evaluation did
demonstrate significant relief of discomfort.  Some studies have evaluated 2% lidocaine jelly use
during complex cystometric evaluation in neurogenic populations, indicating a surprising
increase in detrusor overactivity with 2% lidocaine jelly use.  However, few studies have
evaluated the impact of 2% lidocaine jelly in a non-neurogenic population. If use of 2%
lidocaine jelly was found to improve discomfort during complex cystometric studies in this
patient population without substantially altering the study’s findings, this could impact clinical
practice in an important way.  Herein, we propose a randomized, double blind, controlled trial for
patients undergoing complex cystometric evaluation.  Patients will undergo routine complex
cystometric evaluation for acquisition of baseline data using a small amount of intraurethral
aqueous jelly for catheter lubrication.  Then, they will be randomized to instillation of either
placebo (additional intraurethral aqueous jelly, 5ml) or intraurethral 2% lidocaine jelly.
Participants then undergo complex cystometry a second time.  Normal variations in studies with
placebo will be compared to variations within the 2% lidocaine jelly group to determine if

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cystometric parameters are altered in any clinically important ways.  Patient discomfort will also
be evaluated by both the patient and the urodynamics advanced practice nurse.
Purpose of Study
This trial will assess whether use of intraurethral 2% lidocaine jelly meaningfully impacts
sensation during filling (i.e., a change of more than 25% of first sensation, first desire to void,
strong desire to void, or maximum cystometric capacity) and determine whether the use of
intraurethral 2% lidocaine jelly meaningfully impacts pain/discomfort, filling metrics, and voiding
metrics.
Hypothesis: In women without known voiding dysfunction being assessed for urinary
incontinence by urodynamic studies (UDS), the use of intraurethral 2% lidocaine jelly during
cystometry and pressure flow study (PFS) will not meaningfully impact sensation during filling
and will decrease discomfort for patients.
Significance of the Study
Patients often complain that urodynamic bladder testing is uncomfortable and even
painful, for some.  Intraurethral lidocaine 2% jelly has been used to demonstrate increased
patient satisfaction with comfort during this procedure.  However, the effect of intraurethral
lidocaine jelly on urodynamic test results has not been fully studied.  Considering that lidocaine
jelly is a local anesthetic, it may have a numbing effect, potentially increasing time to first
sensation and bladder capacity, decreasing ability to empty the bladder, and may potentially
mask detrusor overactivity (DO).  However, if the local anesthetic has no effect on urodynamic

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test results, one may consider changing practice to include intraurethral 2% lidocaine jelly with
urodynamic testing to improve patient satisfaction and comfort.
Background of the Problem
Standard teaching for the performance of UDS is that after completion of the un-
instrumented uroflowmetry, cystometry is completed using plain intraurethral aqueous jelly for
insertion of the transurethral pressure catheter. Clearly, this can be a source of discomfort and
pain for the patient. An alternative to plain lubricant, such as 2% lidocaine jelly, may relieve
discomfort for patients but could theoretically impact or distort important cystometry findings,
e.g., first or strong sensation and presence/absence of DO. Further, voiding could be affected if
numbing the urethra blunts sensory nerves that serve to amplify bladder contractions and
maintain efficient bladder emptying.(1, 2) A recent study of healthy volunteers randomized to
intraurethral aqueous jelly versus 2% lidocaine jelly did not identify any detriment to voiding
efficiency using lidocaine but did find greater interrupted flow patterns and more
electromyography (EMG) activity during micturition when using lidocaine.(3) This study found no
difference in pain perception between groups. Similarly, a meta-analysis of 9 randomized trials
assessing lidocaine jelly versus plain jelly lubrication for office flexible cystoscopy did not
suggest a significant difference in the efficacy of pain control using lidocaine.(4) Conversely, a
different trial that compared water-based lubricant and 2% lidocaine jelly for UDS in women did
find substantially less pain for patients using the lidocaine jelly.(5)
Neither of the above two trials of UDS in women compared participants to themselves to
determine how filling and voiding metrics may change before/after lidocaine jelly was applied. It
remains uncertain whether these parameters would change in clinically meaningful ways with
the addition of lidocaine, and the possible benefit of lidocaine—i.e., decreased discomfort for the

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patient—has not been definitively proven or disproven. Using patients as their own controls, this
proposal aims to determine if the use of intraurethral 2% lidocaine jelly during cystometry and
pressure flow study impacts filling and emptying measures while assessing patient discomfort at
various time points during their procedures.
One prior study utilizing patients as their own control evaluated patients with urgency but
no urge incontinence and reported DO on a repeat cystometry after no DO was observed on
initial cystometry, indicating that lidocaine jelly may increase DO. (6) Additional studies have
explored the effect of intravesical lidocaine on cystometric results within neurogenic populations,
but few studies to date have looked at the effect of lidocaine jelly on cystometric parameters and
DO in the normal population of patients with incontinence in the absence of neurogenic disease.
Methods & Analyses:
Urodynamic testing will be performed in procedure rooms by qualified advanced practice
nurses in the field of female pelvic medicine and reconstructive surgery (FPMRS). Eligible
patients meeting inclusion criteria will be consented for study participation prior to urodynamic
testing.  Standard urodynamic testing will be conducted, i.e., first un-instrumented uroflowmetry,
then cystometry (including leak point pressure assessments, LPP) and a pressure flow study
(PFS) with 1-2ml of aqueous jelly in the urethra. UDS will be completed with a dual-sensor 7-Fr
catheter inserted through the urethra into the bladder and a second 7-Fr catheter in the vagina.
Patch electrodes will be adhered peri-anally in the standard fashion for EMG. Patients will be
filled with room-temperature sterile water at 60mL/min. Volumes at first sensation, first desire to
void, strong desire to void, and maximum cystometric capacity will be recorded. Presence or
absence of DO during cystometry will be documented. Other measures (detailed below) will be
recorded during cystometry and PFS. After the patient voids for her first PFS, she will be

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randomized (1:1) to either additional water-based lubricant (placebo) or lidocaine 2% jelly
(5mL).
Randomization will be stratified by presence/absence of DO on the initial cystometry. A
balanced randomization scheme will be generated with equal numbers of placebo and lidocaine.
Identically appearing study drug syringes will be placed in consecutively numbered opaque
envelopes by an unmasked study coordinator not participating in the procedure visit or study
analyses. Both the urodynamic nurse and patient will be blinded to the type of lubricant.
After randomization, the urethral catheter will be removed and 5mL of either placebo or 2%
lidocaine will be injected into the urethra. The patient will sit for 5 minutes to allow lidocaine to
take anesthetic effect.  The catheter is then replaced, and cyostometry and PFS will be
repeated. A continuous pain scale from 0 to 100 (visual analog scale) will be used by the patient
to report her pain level during cystometry #1 (during catheter insertion and at maximum
cystometric capacity), PFS #1, overall UDS #1, cystometry #2 (during catheter insertion and at
maximum capacity), PFS #2, and overall UDS #2 discomfort.  At the end of the procedure, the
urodynamic nurse will also provide a subjective assessment of patient discomfort.
Planned Analyses & Power Calculation:
The primary outcome is the volume at which a participant perceives a strong desire to
void.  Statistical analyses will estimate the confidence interval for this outcome measure
between the two arms of the study (i.e., using 2% lidocaine vs. aqueous jelly) through the
standard calculation for the difference in means when standard deviations of the two arms are
unknown, i.e., through the Student’s t distribution.  As it is thought that there will be no
difference in the mean value of the two arms, the study will be designed as an equivalence trial.
Since DO may alter findings, it is planned to stratify the randomization for DO in order to insure
a balance between the arms for this variable. Prior to randomization, each patient will undergo a

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baseline standard cystometry without lidocaine, and DO (present or absent) will be obtained
from this evaluation.  The observations from this baseline cystometry provide for an interesting
and novel analysis: the baseline measure of volume at strong desire to void may serve as a
covariate to adjust for individual patient variability.  That is, comparisons of the difference in the
baseline measure and the experimental measure will provide a patient “standardized” evaluation
of her additional volume following the baseline.  Analysis of the primary outcome will account for
patient variability with standardization by the value of the baseline measure.
Beyond the primary outcome cystometric evaluations are numerous secondary
outcomes such as pain/discomfort with filling and emptying, presence/absence of DO, and
emptying metrics including flow rates, post-void residual, EMG activity, and detrusor pressures
(max and at peak flow). Continuous measures will use the Student’s t distribution as with the
primary outcome.  Binary and ordinal outcomes will be evaluated using logistic regression. The
use of logistic regression for the ordinal outcomes is through the proportional odds model and
combines with the cumulative logit link.  All of these evaluations may incorporate the baseline
urodynamic study metrics as a covariate (as described above for the primary outcome).
Assuming an average strong desire to void during cystometry (with plain lubricant gel) of
300mL, standard deviation of 100mL (3, 5), a non-inferiority margin of 75mL (i.e., 25% of
300mL), Power (1-β) of 0.80 and α of 5%, 31 participants per study arm (i.e., 62 total) are
needed to demonstrate “equivalence” in sensation during cystometry using plain lubricant gel
versus lidocaine gel. Allowing for 12% participants being unable to complete the second half of
the UDS, a total of 35 participants per study arm (i.e., 70 total participants) will be enrolled.
In the placebo group, the data from the two filling cystometry tests can be compared
(sensation metrics, DO presence/absence, and compliance) to establish “normal variability”.
Anecdotally, patients commonly tolerate a second fill better. With this normal variability better

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defined, we will be able to assess for changes attributable to the lidocaine in the group receiving
the anesthetic jelly—specifically, whether volume of first sensation or bladder capacity is
altered.  We can also assess lidocaine’s impact on bladder emptying by comparing voiding
metrics.  In patients with repetitive DO on their first cystometry, we will be able to assess
whether they continue to demonstrate DO on their second cystometry with lidocaine.
Primary Outcome: Assess whether use of intraurethral 2% lidocaine jelly meaningfully impacts
sensation during filling (specifically, strong desire to void).
Secondary Outcomes: Determine whether the use of intraurethral 2% lidocaine jelly
meaningfully impacts the following:
Pain/ Discomfort
1. Measured by a visual analog scale during cystometry (catheter insertion and at
maximum cystometric capacity), during PFS, and post-procedure
2. Provider perception of patient discomfort
Filling Metrics (besides sensation)
3. Presence/ absence of detrusor overactivity (DO)
4. Compliance (ΔVolume/ΔPdet)
Voiding Metrics
5. Maximum flow rate (mL/sec)
6. Voiding pattern: normal, intermittent, interrupted
7. Detrusor void (yes/no) vs. Valsalva vs. mixed void
8. Voided volume and post-void residual (mL)
9. Voiding efficiency, i.e., voided volume/ (voided volume + PVR) (3)

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10. Pdetmax (cm H2O)
11. Pdetpeak flow (cm H2O)
12. EMG activtity
Participant Eligibility
Inclusion Criteria
Exclusion Criteria
Female patients
 Diagnosis of pelvic pain, interstitial cystitis, or
bladder pain syndrome
>18 years of age
 Known neurogenic disease impacting voiding/
continence (e.g., Parkinson disease, multiple
sclerosis, myasthenia gravis, recent stroke)
Already scheduled (or being scheduled) for UDS
to assess urinary incontinence
 Active UTI
Able to speak and read in English
Pelvic organ prolapse that is unable to be easily
reduced
Pregnancy or breastfeeding
Allergy or hypersensitivity to lidocaine or local
anesthetics
Ethical Conduction
The study site will have a principal investigator and study coordinator, both skilled in
conduct of IRB-approved clinical research, responsible for obtaining and appropriately
documenting informed consent of each patient before beginning any study related procedure.
Once patients have completed informed consent and have enrolled, each participant will be
assigned a Participant ID that is an anonymous patient study number.  Only the research
coordinators and the site PI will have access to the list linking medical record number to
participant ID.  A research coordinator not involved in the care of the patient will have
knowledge of whether a patient received lidocaine jelly or placebo (water based lubricant).  The
research coordinator and site PI will have the responsibility for securing original source
documents containing any identifiable patient data.  Each patient’s study documents will be kept

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under an individual tab in a binder, and the binder(s) will be stored in a locked cabinet and
office.  All information collected about the subject during the course of this study will be kept
confidential to the extent permitted by law.  Besides the specified study team, other access to
study records or data would only be by the IRB or the study sponsor (SUNA) at their request.
All information the subject has provided will be kept in a research record and stored in a locked
office and on a secure, password protected computer.  Research information will not be made a
part of the participant’s regular medical record.  There is no personal information (name, social
security number, etc.) about the subject that is associated with subject’s research data; a
Participant ID number will indicate a subject’s identity on the research records.  Patients
routinely are escorted to exam rooms alone, but they may choose to have a family member or
spouse present if that is her preference.  The informed consent and the history and exam
findings will be collected in a private room.  The informed consent will be written and provided in
English.  Either the research coordinator or another member of the research team (PI or co-
investigator) will be obtaining the consent, and the patient will sign and date/time her name to
indicate understanding, which will be observed and countersigned by the person obtaining the
consent.  No matter what position of authority a research member has, the subject will be
assured of the right to refuse to participate and/or the right to withdraw at any point in the study.
The urodynamics nurse will be trained to minimize discomforts during the procedure.
A patient’s Participant ID number will be provided to the central data collecting center
(UTSW) with no personal information.  Further, data will be entered using REDCap, a Web-
based, HIPAA-complaint tool used by many major medical institutions.  REDCap facilitates
electronic form building and data collection.  It has an automatic audit trail, report builder
capability and data quality module.  REDCap can export data to SAS, SPSS, R, STATA, or
Microsoft Excel.   The REDCap database will reside on a secure UTSW server with continuous
backup.  Only authorized personnel with designated rights can access this study, and that at

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various levels.  For example, a coordinator will be able to enter and check data, but cannot
design screens.  REDCap provides a protocol event schedule where specific forms are linked to
events (visits) in the protocol.  Authentication used in the REDCap application is compliant with
the UT Southwestern Medical Center’s Health System password and security standards.
Project Timeline
Research Task
Projected Time
Course
Completion of IRB application, site review, project start-up processes,
registration with clinicaltrials.gov
3 months
Participant recruitment, data collection (anticipating 5-6 procedures/ month)
12 months
Data analyses
1 month
Manuscript preparation/ submission/ edits, SUNA presentation preparation,
final data entry in clinicaltrials.gov
2 months
TOTAL
18 months
Study Budget
Please see appendix A.  Given that we will be conducting a 2nd CMG and PFS on
patients already having urodynamic studies performed, we will not need any additional supplies
other than the randomized jelly syringes.  A registered nurse will prepare blinded jelly syringes
of lidocaine vs. aqueous jelly solution.  Research coordinator/urodynamicist time is included in
the study budget.  Salary support includes time for the nurse practitioner and/or physician(s) to
submit to the IRB, VELOS, clinicaltrials.gov, and data entry within REDCap system, as well as
time for consenting patients and performing additional complex cystometrogram with pressure
flow study.  It is estimated that the consent process and additional procedure time will be
roughly 150 hours for 70 patients over the course of 12 months.  Additional data entry support
may be required, and this is calculated in the budget, as well.
Research Environment

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UT Southwestern Medical Center (UTSW) is a large, research-oriented university, which
provides an exceptional and highly interactive scientific and intellectual environment, as well as
an extensive array of core laboratory and support facilities. UT Southwestern’s research faculty
include 22 members of the National Academy of Sciences, 15 members of the Howard Hughes
Medical Institute, and 6 Nobel Laureates. The university supports an extensive number of seminar
series, which routinely host outside speakers who are leaders in their fields.  In addition, individual
units and laboratories on campus support a wide variety of works-in-progress meetings and
journal clubs, which provide abundant opportunities for scientific and collaborative interactions.
The environment at UTSW is structured to encourage and support interactions between basic
scientists and clinicians. The intellectual environment in the Department, as well as in neighboring
departments and across campus, is outstanding. It provides a tremendous resource of expertise
to the PI and SUNA for potential proposed studies. Numerous investigators on campus, who
are leaders in their fields, work in areas closely related to the research interests of SUNA.
UTSW Outpatient Building FPMRS Clinic: The UTSW Female Pelvic Medicine &
Reconstructive Surgery (FPMRS) clinic is staffed by Drs. Rahn, Schaffer, Florian, and Corton, 2
FPMRS fellows, and 2 nurse practitioners. The clinic is located in a building adjacent to Clements
University Hospital. This outpatient clinic is fully equipped with 5 examination rooms and a
urodynamic laboratory. Available equipment includes a Laborie® Aquarius XLS urodynamics
system, Wolf® cystoscopy equipment, 2 portable Pathways 10 electrical stimulation units, 3
Uroplasty Urgent PC® Neuromodulation Systems, and a urodynamic chair. One bladder scanner
is present in the clinic. Physicians see patients in nine ½-day sessions per week in this clinic and
perform office diagnostic cystoscopy, periurethral bulking and Botox® injection. The nurse
practitioners see patients 5 days per week for non-surgical management, including pelvic floor
rehabilitation, pessary management, biofeedback, electrical stimulation and urodynamics. One
nurse practitioner (the PI for this proposal) is permanently housed in this clinic so that she is

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available 5 days per week for recruitment as well as treatment of patients in clinical studies.  She
conducts approximately 24-40 urodynamic bladder tests per month.  In 2013/14, 1,721 patients
were seen in the UTSW FPMRS Clinic.
Our division also participates in NIH funded multi-site clinical research trials through the
Pelvic Floor Disorders Network, providing a strong foundation in clinical research.  Research
support is available by on-site registered nurses, clinical research coordinators, &
biostatisticians, who can aid in the statistical data analysis and data entry.
The principal investigator, Christina Hegan, MS, APRN, WHNP-BC, is a current member
of the Society of Urologic Nurses & Associates (SUNA), serving as Urodynamics Special
Interest Group Leader.  She has also presented at the 2018 SUNA urologic conference
meeting, served on two patient fact sheet task forces, and recently submitted an abstract for
presentation at the 2019 SUNA urologic conference.  She has achieved several
accomplishments in the last two years, including publication of two literature reviews online
through the Interstitial Cystitis Association (ICA), three magazine articles published in the ICA
Update, and a chapter published in an international textbook.  She is currently serving as an
interventionist in three NIH funded multi-site clinical research trials through the Pelvic Floor
Disorders Network, and she has completed one phase 2 multi-site industry sponsored clinical
trial as co-investigator.
Faculty sponsor & co-investigator, Dr. Joseph Schaffer, will be an important mentor in
this project.  With his many years of experience in pelvic floor medicine and reconstructive
surgery, Dr. Schaffer has a strong record of accomplishment, producing quality based,
statistically significant, and well-designed studies.
Additionally, co-investigator Dr. David Rahn will be an integral contributor and mentor on
this project.  Dr. Rahn also has a strong record of accomplishment, including receiving a recent

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NIH grant for an investigational trial studying the role of vaginal estrogen in surgical healing.
His study may help change practice by providing substantial proof or disproof of vaginal
estrogen’s ability to aid in the healing process, which has long been speculated.
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2. Jung SY, Fraser MO, Ozawa H, Yokoyama O, Yoshiyama M, De Groat WC, et al. Urethral
afferent nerve activity affects the micturition reflex; implication for the relationship between
stress incontinence and detrusor instability. The Journal of urology 1999 Jul;162(1):204-12.
3. Kisby CK, Gonzalez EJ, Visco AG, Amundsen CL, Grill WM. Randomized Controlled Trial to
Assess the Impact of Intraurethral Lidocaine on Urodynamic Voiding Parameters. Female
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5. Ozel BZ, Sun V, Pahwa A, Nelken R, Dancz CE. Randomized controlled trial of 2% lidocaine
jelly versus water-based lubricant for multi-channel urodynamics. International
urogynecology journal 2018 Sep;29(9):1297-302.
6. Edlund, C., Peeker, R., & Fall, M. (2001). Lidocaine cystometry in the diagnosis of bladder
overactivity. Neurourol Urodyn, 20(2), 147-155.