The study will be registered on clinicaltrials.gov after IRB approval. Institutional Review
Board (IRB) approval will be received.
All women 18 years of age and older with bothersome overactive bladder symptoms who are
receiving care at Walter Reed National Military Medical Center (WRNMMC) in the urogynecology
clinic will be eligible for the study.
All study participants will undergo a complete intake assessment to include a history,
physical exam, post-void bladder residual volume assessment via straight catheterization or
ultrasound, and counseling on treatment modalities for OAB using the AUGS handout to include
behavioral and dietary modifications, physical therapy, oral medications, onabotulinumtoxinA
and neuromodulation. Patients desiring treatment with onabotulinumtoxinA will be scheduled
for the procedure. Patients do not have to fail prior treatment options in order to qualify
for bladder BOTOX. This is all standard of care in our practice. All patients meeting the
inclusion and exclusion criteria will be offered enrollment in this study. Enrollment will be
done by the research team, who typically are also the clinicians. No patients will be
pressured or coerced into participating in the study.
Prior to the procedure appointment, participants will be consented for participation in the
study and asked to complete demographics data sheet, 24 hours bladder diary, OAB-q SF, PGI-S,
PISQ-IR. OAB-q SF is a standard of are in our practice, all other questionnaires patient will
fill out for the purpose of this study.
The procedure will be performed at Walter Reed National Military Medical Center either in
clinic setting or in the operating room. All patients who plan to undergo the procedure in
clinic will be offered a pre-treatment anxiolytic with a single dose of 5-10mg of oral
diazepam, which is standard practice at this institution. Patients undergoing the procedure
in the operating room, will be given sedation medications as per standard of care. As
standard of treatment, patients will also be given a prescription for an antibiotic - either
nitrofurantoin 100mg to take orally twice daily for 3 days starting the day of the procedure,
or trimethoprim-sulfamethoxazole 800mg-160mg to take orally twice daily for 3 days starting
the day of the procedure depending on patient's allergy profile.
The principal investigator will make randomized assignments using the RAND function in excel.
The first 32 random numbers will be assigned to BOTOX arm and the second 32 numbers will be
assigned to XEOMIN arm. Each assignment number will be placed in a sealed envelop by the PI.
The sealed envelops will be opened by the treatment provider the day of the scheduled
procedure. The envelop will reveal the medication assignment to the provider. After the
provider reveals the medication only to him/herself (not the patient), the appropriate
medication will be obtained from the pharmacy and administered to the patient.
The patient will be blinded to the treatment allocation. The drug will be obtained from the
pharmacy on the day of the procedure by the treatment team. Either onabotulinumtoxinA or
incobotulinumtoxinA (as determined by the allocated assignment), will be reconstituted in 10
milliliters of injectable saline by the treatment team prior to entering the patient's room,
to keep the patient blinded. The bladder will be filled with 20ml of 2% viscous lidocaine
through the urethra 15 to 20 minutes prior to the procedure per the Urogynecology department
standard operating procedure for intradetrusor onabotulinumtoxinA injections. Operative
cystoscopy will be performed, and an adjustable-depth injection cystoscopy needle will be
used to inject the blinded study drug (either 100 units of onabotulinumtoxinA (Botox®,
Allergan) or 100 units of incobotulinumtoxinA (Xeomin®, Merz Pharmaceutical)) with the needle
depth set to 3mm. Injections will be performed by either a board-certified staff
Urogynecologist, or fellows or residents working under their direct supervision of the
board-certified staff urogynecologist. An injection cystoscopy needle will be set to 3mm and
used to inject 0.5mL reconstituted study medication at each injection site, approximately 1cm
apart along the posterior bladder wall making sure to avoid the trigone, for a total or 20
injection sites (4 rows of 5 injection sites). After the completion of the procedure,
patients will be asked to start taking their prescribed antibiotics and to continue them for
3 days.
If a known UTI was inadequately treated prior to procedure appointment, or if there is
evidence of an active infection at the time of cystoscopy, the intravesical injection will
not be completed and patient will be rescheduled.
Participants will have a follow-up appointment in 2-6 weeks following the procedure in
person, via phone or email. At the follow-up visit patients will be asked to complete a
24-hour bladder diary, OAB-q SF, PGI-I, PGI-S, PISQ-IR surveys. The surveys will either be
read or emailed to the patient based on patient's preference. Patients will be asked
regarding urinary tract infection (UTI) symptoms and whether they needed clean intermittent
catheterization (CIC). The electronic health record (EHR) will also be reviewed to confirm
whether UTI has occurred or if CIC needed to be done. Patients will be asked whether they are
experiencing painful urination, urinary frequency, urinary urgency, or blood in their urine.
If patients answer yes to any of those questions, they will be asked to provide a urine
sample. If this follow up is being done in person, then a urine sample will be obtained via
straight catheterization during the appointment. If the follow up visit is being done
virtually, patient will be asked to come into clinic or laboratory and provide a urine sample
via straight catheterization or clean catch for urinalysis and urine culture to assess for
UTI. If infection is present, patients will receive appropriate antibiotics based on culture
sensitivities. Patients found to have an active infection at the time of postprocedural
follow-up will be asked to complete the study questionnaires 2-4 weeks following treatment of
infection. Patients will also be asked if they experienced any other symptoms following the
procedure that concerned them and any symptoms reported will be recorded.
Participants who experience initial relief in their symptoms following injection of the study
medication but then experience recurrence of symptoms will be eligible for repeat injection
provided it has been at least 12 weeks from prior injection and the total dose of
onabotulinumtoxinA/incobotulinumtoxinA does not exceed 400 units in a three-month time frame,
as is standard of care.
Six to nine months following the treatment, patients will be contacted via phone or email and
asked to complete a 24-hour voiding diary, OAB-q SF, PGI-I, PGI-S, and PISQ-IR surveys for
final assessment of symptoms following treatment. They will again be asked regarding adverse
events. The questionnaires again will either be read to the patient via phone or emailed
based on patient's preference.
This research study is a single-blind study. Unblinding of subjects will be performed at the
conclusion of the study after enrollment is closed and data collection is complete.
Participants will not be notified of their group assignment unless it is requested after the
completion of the final follow up encounter. If the participant would like to know their
group assignment, they will contact the PI who will release that information to them after
the conclusion of the study. Study participants who request to be un-blinded as to their
randomized assigned group early will need to be withdrawn from the study. The participant
will supply a request in writing to the PI. Any data regarding that participant will be
removed from the records and that assignment number will be noted as withdrawn. A memorandum
for record will be created outlining the subject's request and both the MFR and subject's
written request will be maintained with the data collection for reference. In the event of an
emergency, there is a way to find out which one the participant is receiving. If there is a
medical emergency that may require unblinding prior to the conclusion of the study, the
research team will work in coordination with the subject's primary care or emergency provider
to determine if unblinding is necessary and make that information available to them as
needed.