Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03089671 |
| Other study ID # |
FPMRS McD 001 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
December 7, 2017 |
| Est. completion date |
July 21, 2021 |
Study information
| Verified date |
August 2021 |
| Source |
Mount Sinai Hospital, Canada |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Background: The risk of ureteric injury at the time of pelvic reconstructive surgery can be
as high as 3% and the American College of Obstetricians and Gynecologists has stated that
intraoperative cystoscopy should be done after all such procedures. Intravenous indigo
carmine was routinely given during surgery to colour the urine bright blue and allow for
assessment of ureteric integrity. In 2014, indigo carmine was no longer available worldwide
and since then, surgeons have been searching for suitable alternatives. Vitamin B is a water
soluble vitamin that colours the urine bright yellow and can be given immediately before
surgery to help with ureteric visualization. Alternatively, 5% dextrose in water (D5W) can be
used as the instillation fluid during cystoscopy to allow for urine jet visualization due to
the difference in fluid viscosity. Both agents have been shown to be better than instillation
with normal saline and are affordable and accessible in Canada.
Objective: To identify which agent is superior for intraoperative ureteric visualization at
the time of cystoscopy by determining the difference in detection rate of both ureteric jets
using either preoperative oral vitamin B or intraoperative cystoscopic distension with D5W.
Methods: This study will be a three-site (Mount Sinai Hospital, Sunnybrook Health Sciences
Centre, Women's College Hospital), double-blinded, randomized control trial whereby female
patients undergoing pelvic reconstructive surgery will be randomized to receive either
preoperative vitamin B or intraoperative D5W cystoscopic instillation fluid. Parameters
measured during surgery will include whether both ureteric jets were seen, time to
visualization of both ureters, colour of jets, and surgeon satisfaction. Patients will also
be seen at one week after surgery to assess for urinary tract infection. Sample size
calculation based on previous studies demonstrated a need for 119 patients per study arm.
Anticipated Clinical Significance: The findings of this study will be relevant to all
surgeons performing intraoperative cystoscopy where ureteric visualization is required. The
investigators believe the outcome of this study will help make cystoscopy shorter and more
efficient for surgeons who often feel the pressure of time constraints within the operating
room setting. In turn, decreasing the time of cystoscopy may reduce operating times which
will benefit both the patient and hospital.
Description:
Study Design: This study will be a double blinded, randomized control trial (RCT) to compare
detection rates of one and both ureteric jets at the time of intraoperative cystoscopy using
either vitamin B or D5W. This will be a multicentre study with patients being recruited from
Mount Sinai Hospital, Sunnybrook Health Sciences Centre, and Women's College Hospital.
Recruitment and Consent: Female patients undergoing pelvic reconstructive surgery where
cystoscopic ureteric visualization is required will be recruited from Mount Sinai
Hospital/Sunnybrook Health Sciences Centre/Women's College Hospital at their surgical consult
in the clinic/ambulatory setting. At that time, one of the study investigators (not the
operating physician for that particular patient) will describe the study to the patient and
give her the study consent form if she is interested in participating. For any patients
recruited or considering the study, they will be asked to stop all vitamin supplements one
week before surgery. If the patient cannot decide on the day of the surgical consult, they
can go home with an unsigned consent form to review the study and on the day of surgery they
will once again be asked if they would like to participate in the study by a study
investigator (not involved with the patient's surgery). Once the patient has read and
voluntarily signed the consent form, the same study investigator will open a sequentially
numbered opaque sealed envelope that will provide a study identification number for the
patient and randomize the patient to either receiving a preoperative dose of vitamin B or
intraoperative cystoscopic distension with D5W. The patient and operating surgeons will not
be made aware of the group the patient was allocated to.
Sample Size Calculation: There is only one study in the literature that has commented on
ureteric visualization after vitamin B2 ingestion. In this study, they report a 72% detection
rate. If we consider a 15% difference in detection rate to be clinically significant, then
with a power of 0.8 and an alpha of 0.05, the minimum number of patients required per group
would be 113. We anticipate a 5% drop out rate after consent due to intraoperative issues.
Therefore, we will recruit 119 patients per study arm to be included in the final analyses
(n=238).
Method: Upon recruitment to the study, the study investigator that did the consent will then
complete the Initial Information Form where the following information will be collected from
the patient (this information is also already available in the clinical record):
- Age
- Parity
- BMI
- Smoking status
- Diabetic status
- Menopausal status
- Immunocompromised status
- Pelvic Organ Prolapse-Quantification (POP-Q) stage
- Preoperative use of vaginal estrogen
- History of recurrent UTI
Patient packages will be created and assigned a patient number. For those randomized to the
vitamin B group, the package will consist of a pill of vitamin B2 (containing 100mg of
riboflavin) that is inside an opaque gelatin capsule that is matched to a litre bag of normal
saline that is wrapped in an opaque covering. For those randomized to the D5W group, the
package will consist of a pill of cellulose that is inside an opaque gelatin capsule that is
matched to a litre bag of D5W that is wrapped in an opaque covering. These packages will be
couple with the patient according to her randomization group in the preoperative area.
In the preoperative area, all patients will be given the pill in their package by mouth 60 to
120 minutes before the start of surgery. The covered bag will then accompany the patient to
the operating room and will be set up as the instillation fluid for cystoscopy. This way, the
patient and operating team will be blinded to what agent was used for ureteric visualization.
Cystoscopy will be done using a standard diagnostic 70 degree cystoscope.
In the preoperative area and in the operating room, the following data will be collected by a
study investigator that is not part of the operating team:
- Time pill was given
- Time cystoscopy was started
- Time surgeon started to look for ureteric jets
- Time first ureter was visualized
- Time second ureter was visualized
- Colour of jet (clear, pale yellow, or bright yellow)
- If cystoscopy is repeated to look at ureters, above measures are captured again
- If fluorescein (0.25mL by iv injection) is used as a rescue agent, reason why, time it
was given, and time jets were seen are recorded (in order to allow for an adequate time
to determine whether the study agent has worked, fluorescein cannot be used any earlier
than 10 minutes from the start of cystoscopy)
- Surgeon satisfaction of ureteric visualization during that specific case is rated on a
Likert scale from 1 to 5
- Primary surgeon's guess at the agent that was used to visualize ureters
Between post-operative days 3 and 10, the patient will present to clinic and information on
length and type of catheter use, as well as antibiotic use after surgery will be recorded.
Patients will also give a catheter urine specimen to be sent for culture and sensitivity.
DATA ANALYSIS Baseline characteristics and follow-up measures will be summarized using
descriptive statistics (mean, SD, median, and range for continuous variables, count and
percent for categorical variables). Continuous variables will be summarized using means and
standard deviations, and will be compared between groups using Student's t-tests. Categorical
variables will be summarized using counts and percents, and compared between groups using
Chi-squared tests. A P-value ≤0.05 will be considered significant for all statistical
analyses performed.
