Urolastic® versus Bulkamid® in treatment of female stress incontinence: randomized controlled trial.

Stress urinary incontinence (SUI) is a common complaint which significantly
impacts the quality of life of many women. It is caused by either sphincter
abnormalities and/or urethral hypermobility and is characterized by involuntary
urine loss during coughing, sneezing, physical exertion or sudden changes of
position (Blaivas JG, 1997; Abrams P, 2003). Approximately 35% of women >18
years are suffering from involuntary urine loss. At the age of 60 years, the
rate rises to 45% in Europe (Mohr S, 2011). Nowadays mid-urethral sling (MUS)
procedures are widely used and highly effective in the treatment of SUI with a
relatively low complication rate. Based on industry estimates there were
approximately 250,000 of these procedures performed in the USA in 2010
(http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProst
hetics/UroGynSurgicalMesh/ucm345219.htm.) Although the efficacy of MUS
procedures is high, there is still a failure rate of about 10-20%.
In July 2011, the FDA issued a safety communication regarding the use of
synthethic vaginal mesh for the treatment of pelvic organ prolapse and urinary
stress incontinence stating that serious complications are not rare. According
to this communication, the FDA received from January, 1 2008 through September,
30, 2011, 1,876 reports of complications associated with surgical mesh devices
used to repair SUI. The most common complications reported through Medical
Device Reports in descending order of frequency, include: pain, mesh erosion
through the vagina, infection, urinary problems, recurrent incontinence, pain
during sexual intercourse (dyspareunia), bleeding, organ perforation,
neuro-muscular problems and vaginal scarring. Many of these complications
require additional medical intervention, and sometimes require surgical
treatment and/or
hospitalization.
(http://www.fda.
gov/medicaldevices/safety/alertsandnotices/ucm262435.htm) Therefore there is
definitely a place for less invasive treatment of SUI. According to the study
of Robinson Anders and colleagues, the majority of women with SUI would prefer
a minor procedure with a lower risk of complications and are content to accept
a lower success rate (Anders, R.D, 2003). Moreover, study of Steven Petrou has
also shown that SUI patients are willing to accept a relatively low success
rate for injectable therapy compared to open surgery (Petrou, S.P, 2006).
Therefore less invasive therapies such as injectable therapy is an attractive
option to patients who accept this form of treatment despite their lower
success rate in comparison with more invasive methods as MUS.
Urethral bulking agents with specially designed injection devices are one of
the minimally invasive options in the treatment of stress urinary incontinence.
Bulking agents can be useful when patients experience MUS failure, have severe
comorbidity (and thus a contraindication for general anesthesia), or when
patients prefer minimally invasive surgery. The ideal bulking agent should be
easily injectable under local anesthesia, should be permanent and maintain its
shape, volume and flexibility and therefore its mechanical effect, and should
be hypoallergenic and non immunogenic. One of the examples of bulking agents is
Bulkamid®, which consists of a biodegradable gel (polymer gel composed of 2.5A%
cross-linked polyacrylamide and 97.5% non-pyrogenic water) containing non
degradable particles. The gel is injected trans urethrally at 3 places around
the bladder neck, which results in the compression of the urethra. Although it
contains non-biodegradable particles it stays liquid and is not easily
encapsulated in scar tissue in the desired shape. Because of gel degradation,
the volume of the implant may shrink and thereby diminish the therapeutic
effect. Recent reports by Lose et al. and Toozs-Hobson et al. show that 135
women with either stress or mixed urinary incontinence have been treated with
Bulkamid and followed for 12 and 24 months. The subjective response rate was
66% and 64% respectively ( Lose, G et al. 2010, Toozs-Hobson et al , 2011).
Urolastic® has been developed as an improved alternative to the existing
urethral bulking agents. Urolastic is a polydimethylsiloxane (PDMS) polymer. It
is a minimally invasive, easy to inject and polymerizing in situ into a uniform
elastomer within seconds after application. It remains flexible and adapts
itself to the shape of the environment during injection, reducing the chances
of migration. Reflux of the material after injection as a consequence of the
interstitial pressure is unlikely after polymerization. The product is
biocompatible; it is not biodegradable, resulting in a long term effect. The
study by Zajda 2013 shows that after one year of treatment 72% of patients did
not have any urinary incontinence whereas the Stamey incontinence grade
improved significantly (Zajda et al., 2013) Furthermore, the results of 24
months follow-up after Urolastic injection indicate that 66% of the patients
show significant improvement of stress urinary incontinence (SUI) (Zajda et.al
2014 submitted). In a recent study by Futyma et al it has been shown that the
objective success rate in 54 patients with recurrent SUI was 59.3% including 45
patients who are completely dry 12 months after the procedure (Futyma et al
2014).
Since Bulkamid ® is a gel, it can degrade, and thereby lessen the effect on
continence. Frequently (30% of the cases), repeated injections are necessary.
Urolastic ® remains its shape and therefore the re-injection rate is much lower
(approximately 0-2%) (Lose G et al.2010, Toozs-Hobson P et al, 2012).
In order to compare these two injectibles we propose a prospective randomised
controlled trial to evaluate the subjective and objective outcome of
Urolastic® or Bulkamid® in patients with symptomatic stress incontinence, and
the number of re-injections in both groups.

Subjective cure of urinary stress incontinence at 12 months after intervention
and comparison of a new bulking agent Urolastic ® with Bulkamid® in the
treatment of stress urinary incontinence.
Our hypothesis: based on our study and literature available we expect
Urolastic® as compared with Bulkamid® to be more successful in correction of
stress urinary incontinence.
Primary objectives:
* Comparing the re-injection rate between Urolastic ® and Bulkamid ® treatment



Secondary objectives:
- Subjective cure of stress incontinence at 6 weeks and one and two years
follow up after either Urolastic ® or Bulkamid® treatment
- Objective cure of urinary stress incontinence
- Improvement of stress incontinence
- Complications during and after the procedure
- Patient satisfaction

The proposed research concerns a single-centered, single blinded, randomized
controlled clinical trial and is aimed to determine the effectiveness of
Urolastic® compared to Bulkamid® in women with urinal stress incontinence. The
participating hospital is Isala kliniken Zwolle (coordinator H.W.F van
Eijndhoven, MD,PhD and M.K. Engberts, MD, PhD).
After inclusion patients will be randomly assigned to one of the study groups.

Urolastic ® or Bulkamid ®

As we compare two strategies that are already applied in current practice, no
additional risks from both procedures are expected. In several retrospective
studies, it has been shown that injection of bulking agents is a safe
procedure. Complications rarely occur and are usually minor, consisting mostly
of temporary urinary retention, and urinary tract infection