Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT02965313 |
| Other study ID # |
H16-02085 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 2016 |
| Est. completion date |
November 2023 |
Study information
| Verified date |
May 2022 |
| Source |
University of British Columbia |
| Contact |
Nicole Koenig |
| Phone |
604-806-9829 |
| Email |
nkoenig[@]providencehealth.bc.ca |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This is a Canadian, multi-centre, double-blind randomized controlled trial of an innovative
vaginal surgery technique for correction of pelvic organ prolapse (POP) in women. Vaginal
surgery is preferred as minimally invasive, however the investigators do not know if
materials such as synthetic polypropylene mesh improve success, durability and
cost-effectiveness long-term. The investigators principal goal is to compare the experimental
bilateral sacrospinous vaginal vault fixation with synthetic mesh arms (BSSVF-M) to the
current standard of sacrospinous ligament suspension with synthetic sutures (SSLS) over a
timeline of 2 years. Patients and evaluators will be blind to technique.
Description:
Background and Rationale:
The pelvic floor comprises muscles, nerves and a fascial network with dynamic, elastic
ligaments of support. Pelvic organ prolapse (POP) occurs when the capacity to accommodate
pressure and stretch is exceeded and increases with childbirth and aging. One in five women
need surgery for POP. POP suspension performed vaginally is among the most important ideas in
gynecology in the past few decades, however the investigators do not know which technique is
best. The principal applicant has developed a novel surgery: bilateral sacrospinous vaginal
vault fixation with synthetic mesh arms (BSSVF-M), which may be more successful, durable and
cost-effective than standard sacrospinous ligament suspension with sutures (SSLS) and may
thus become the preferred vaginal POP surgery both nationally and internationally. A Cochrane
review on surgical management of POP concluded that "adequately powered RCTs with blinding of
assessors are urgently needed […] they particularly need to include women's perceptions." The
OPTIMAL trial, a large RCT comparing 2 POP surgeries, established a stringent definition of
success using a composite outcome of objectively measured POP, subjective improvement and the
need for another treatment for POP recurrence.
Identifying the best way to surgically suspend the vagina for POP can make the difference
between a woman who can enjoy a desired level of physical activity at work or play, empty her
bowel and bladder without concerns, engage in a normal sexual life and a woman who can't
perform these basic activities without discomfort, pain, worry and shame. The vaginal
approach for pelvic surgery offers less pain, a shorter hospital stay, a faster recovery and
no external incisions. However, what is the safest, most durable, most cost-effective vaginal
POP surgery? Prior operations have produced unacceptable complications or a need for
reoperation for POP recurrence. Further suffering for women and unacceptable healthcare costs
ensued. Because seniors (over age 65) are the fastest growing age group in Canada, the CIHR
states research into aging should be prioritized. By 2031, Statistics Canada estimates the
number of senior women to reach 5.1 million or 24% of the total female population. Women have
longer life expectancy than men. The burden of POP increases with age; 1 of 2 women over 80
experience pelvic floor dysfunction. For some aging women, vaginal surgery is the only option
because of comorbidities precluding more invasive or lengthier open abdominal surgeries.
Currently, there is true clinical equipoise between BSSVF-M and SSLS. Our novel mesh
insertion technique, BSSVF-M, offers the advantages of small size, deep, tension-free and
tailored to individual anatomy. This ensures midline restoration of the vaginal axis and
maintains flexibility for normal bladder, bowel and sexual function. Tension-free insertion
of BSSVF-M is a key difference with SSLS, which pulls the vagina tight against ligaments,
causing pain or the return of POP after SSLS. Surgical innovation is important but adoption
of new procedures needs reliable evidence acquired through a rigorous Innovation,
Development, Exploration, Assessment, Long-term study (IDEAL) paradigm.
The investigators have been studying BSSVF-M over the past 9 years. Initial development
included a magnetic resonance imaging study establishing restoration of pelvic anatomy
comparable to normal. An exploratory prospective cohort study followed, showing BSSVF-M to be
safe, easily taught to other surgeons and successful in 77% of women at one year, with the
OPTIMAL composite outcome. This is superior to the reported 60% success of the SSLS and
informed our power calculation for the proposed RCT. An informal survey of 50 Western Society
for Pelvic Medicine surgeons indicated that an average of 14% increase in composite outcome
success would be sufficient to adopt a new vaginal suspension technique. The investigators
are now at the IDEAL assessment stage, where our novel technique warrants an RCT before
widespread adoption. The results of this trial will directly inform surgeons whether mesh
should be used for vaginal repair of POP and how to counsel patients. This trial includes
knowledge translation for women to understand pelvic floor symptoms, related
condition-specific quality of life, sexual health and body image after two vaginal surgery
procedures. A rigorous cost effectiveness analysis will inform different stakeholders and
policy makers regarding cost effectiveness.
Primary Objective:
To compare BSSVF-M vs. SSLS via the OPTIMAL composite outcome measure at 2 years.
Secondary Objectives:
To determine condition-specific urinary, bowel and POP symptoms, quality of life, new onset
pelvic pain, gender-specific body image, sexuality, global improvement, adverse events,
reoperations and health utility up to 2 years post BSSVF-M vs. SSLS. Validated questionnaires
and adverse event schemes will be used. A Markov model will estimate 10-year health benefits
and costs of surgery.
Interventions:
Patients > age 19, symptomatic POP (stage 1-4) randomized to BSSVF-M or SSLS. Both surgeries
are performed through the same vaginal incisions. BSSVF-M uses bilateral synthetic
polypropylene mesh arms for support of the vaginal wall and SSLS uses two synthetic sutures
attached uni- or bilaterally. As both are performed through the same incision, women will not
know their treatment. Group assignment will remain blinded through trial end. Surgeons will
receive group allocation immediately prior to surgery. To diminish bias, research personnel
conducting pelvic exams to evaluate the primary outcome will be blind to the type of
procedure. Patients will be seen and examined at 6 weeks, 1 yr and 2 yrs following surgery.
They will fill out questionnaires. At 6 months postoperatively, they will receive a phone
call and will fill out a questionnaire for health utility purposes.
Recruitment/Timeline:
The investigators anticipate recruiting over 2.5 yrs (fall 2016-spring 2019). Total timeline
for the trial is 5 yrs, to ensure follow-up of all recruited women for 2 yrs postop. The main
centre in Vancouver (2 surgeons) is committed to recruiting 1-2 patients per week or 130
total. Edmonton (1 surgeon), Calgary (1 surgeon) and Montreal (2 surgeons) would recruit 76
patients each. Based on prior experience with the pilot study of BSSVF-M and OPTIMAL, the
investigators anticipate approximately 90% of invited women will volunteer and 5% of those
will change their mind about participation at baseline. Given the NPA performs 4 to 8 vaginal
surgeries for POP per month, the investigators anticipate no recruitment challenges. Based on
surgical volumes and commitment to research, the other sites should also reach targets. All
surgeons are experts at vaginal surgery for POP (including SSLS) and all except one have
performed BSSVF-M. They do not currently offer BSSVF-M outside research studies. According to
national credentialing organizations and our surgical survey, surgeons require at least 5 and
on average 8 procedures to become familiar with a new vaginal POP technique. Assistance with
8 cases will be provided to the surgeon untrained to perform BSSVF-M. In addition, video
instruction will be provided to standardize procedure and materials.
Challenges/Mitigation:
Compliance problems:
Compliance with follow-up may be an issue due to the follow up for 2 years. Patients will be
screened for future compliance at recruitment and the coordinator at each site will follow
each patient quarterly over the 2 years, asking for updated contact information at each time
point.
Loss to follow-up:
The investigators anticipate similarities in loss to follow-up (15%) to OPTIMAL. To mitigate
loss to follow-up, the investigators will reimburse patient parking and traveling costs with
a small stipend.
Unblinding of participants:
In the event of complications arising from either surgery, patients or assessors may become
aware of the group assignment. For example, if a patient develops exposure of the vaginal
mesh, the pelvic examination will reveal this at various time points and surgery may be
needed to remove the mesh exposed in the vagina. This may introduce bias in assessments at
various time points, however it will likely not affect the primary composite outcome measure
at 2 years. Based on our prior experience with BSSVF-M, the investigators anticipate
unblinding complications to be less than 5% of the total sample. The primary surgeon who
deals with complications and need for reoperation is not involved in pelvic examination
assessments. Most complications will be corrected by 2 years, so the blinded assessor at 2
years will be unable to identify group assignment.
Sample size:
179 women/group (358 total). Our Western Canadian survey of 50 surgeons indicated the
smallest clinically relevant difference to change surgical practice would be an absolute
change of 14%. The proportion of success in the control SSLS group was 60.5% in the OPTIMAL
trial and the success rate with BSSVF-M was 77% in our one-year pilot study. Our pilot study
was small and designed to inform a power calculation for an RCT; it did not study long-term
results, cost effectiveness or KT strategies. Studies of mesh vs sutures in surgery for
urinary incontinence indicate that mesh is more successful, durable and cost-effective than
sutures, therefore the investigators expect similar results for POP, with sustained
durability of mesh over time. Our primary analytic strategy, following the example of the
OPTIMAL trial, will include only patients who come for 2-yr follow-up or who were failures on
the last follow-up. Patients who do not come to their 2-yr follow-up but who were failures at
last follow-up will be counted as failures. Sample size was determined based on a two-sample
test of independent proportions, using two-sided µ=0.05, anticipated successful outcome rates
60 and 75%, power=80% and yielded 152 patients/group. To account for an estimated 15% loss to
follow-up (patients who never had a follow-up visit or who were deemed successful on their
last follow-up), similar to the OPTIMAL trial, our sample size was increased to 179 per
group.
Allocation:
Random allocation is via a web-based allocation system. A statistician will generate a list
of random allocations, stratified by surgeon and using randomly sized permuted blocks to
prevent bias in guessing the next treatment allocation. Although all surgeons will be skilled
in both techniques, differences in experience may impact outcomes. By stratifying for
surgeon, the investigators ensure similar numbers of allocations to each treatment in each
hospital.
Patients will be enrolled by research personnel at each participating centre. The site
coordinator will randomize the patient prior to surgery using the web-based allocation
system.
Patients will be blinded to the type of procedure received until 2 years after surgery.
Research personnel evaluating outcomes at each in person visit will be blinded to the type of
procedure received by participants.
Ethics and dissemination
This protocol and the informed consent forms will be reviewed and approved by the
Institutional Review Boards (IRBs) at each participating centre with respect to scientific
content and human subject regulations. The participant education and recruitment materials
(and other requested documents as necessary) will also be reviewed and approved by the
ethical review bodies at each participating centre. Subsequent to initial review and
approval, the responsible IRBs will review the protocol at least annually. Each collaborator
will make safety and progress reports to the IRBs at least annually and within 3 months of
study termination. Any modifications to the protocol will require a formal amendment with
each IRB.
Trained research personnel will introduce the trial to patients who will be shown educational
materials regarding pelvic organ prolapse and the trial interventions. Patients will have an
informed discussion with the participating personnel who will obtain written consent for
participation. Patients will receive information sheets and a copy of the consent form.
All trial-related information will be stored securely at the coordinating centre in
Vancouver. All participant-related information will be stored in locked file cabinets in
areas with limited access. All records that contain names or other personal identifiers will
be stored separately from study records identified by code number. All local databases will
be secured with password-protected access systems. Participants' study information will not
be released outside of the study without the written permission of the participant, except as
necessary for monitoring by government and regulatory authorities. To ensure confidentiality,
data dispersed to trial team members will be blinded of any identifying participant
information.
