Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04478747 |
| Other study ID # |
01072020 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2020 |
| Est. completion date |
December 2027 |
Study information
| Verified date |
January 2024 |
| Source |
Helsinki University Central Hospital |
| Contact |
Tomi Mikkola, Prof. |
| Phone |
+358504271187 |
| Email |
tomi.mikkola[@]hus.fi |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The main objective of the study is to compare subjective efficacy of trans vaginal mesh and
laparoscopic colposakropexy (CSP) in women with an apical prolapse. The CSP group is further
divided into two sub-groups; one where the mesh fixation is only at the apical part of the
vagina, and another where the fixation is also extended to the levator plane.
The secondary outcomes are safety (peri- and post-surgery complications, pain, erosion),
objective efficacy (simplified POP-Q), and re-operation rate. Subjective outcome also
includes the assessment of sexual satisfaction. Cost-effectiveness is studied by comparing
both direct costs and QALYs.
Description:
Pelvic organ prolapse (POP) is defined as an anatomical support defect of the pelvic viscera.
Women's POP is the descent of uterus or vaginal apex with or without concomitant descent of
the anterior (cystocele) or posterior (rectocele) vaginal wall. It is estimated that the
lifetime risk of POP surgery in women is approximately 10-13%, the incidence peak being 20-30
years after the first delivery, which is also the most important risk factor for POP. Other
risk factors include previous hysterectomy, obesity and genetic factors.
The typical POP symptoms are a feeling of bulge, accompanied with urinary incontinence,
defecation problems, and sexual dissatisfaction. First line treatments are conservative, but
if they fail, surgery is indicated.
Native tissue repair of the anterior and / or posterior vaginal wall (colporrhaphy anterior /
posterior) is commonly the first-line operation. The possible concomitant apical prolapse
needs to be suspended which is typically done by either by performing a hysterectomy with
shortening and suspension of the sacrouterine ligaments, or by amputation of the cervix with
suspension of the cardinale and sacrouterine ligaments (Manchester operation). An unsuspended
apical defect will double the relapse rate (20 vs 11%). In most of the apical recurrences
mesh is used to achieve sufficient support. The re-operation rate of any POP in Finland is
10.8% .
In mesh operations the apex can be suspended either transvaginally (TVM) by anchoring the
mesh to the sacrospinosus ligaments, or by doing a colposacropexy (CSP) where the mesh is
attached to the sacrum, mostly via laparoscopy. The CSP techniques vary e.g. the mesh can be
attached only apically or also to the levator plane. If needed, colporrhaphies can be done
concomitantly.
The use of TVM has decreased due to the FDA-warnings and litigations concerning mainly the
risks of erosion and pain. This has lead to withdrawals of mesh products, despite
well-conducted clinical studies indicating that in well-chosen women light-weight small TVM
is not associated with major complications. Currently, no TVM with good quality clinical data
is available. Traditionally, CSP has been considered safer than TVM in regard of erosions and
pain, but the data is scarce. Furthermore, CSP has a longer learning-curve and is a more
time-consuming operation than TVM, whereas hospital stay is shorter.
To the investigators knowledge, there is only one published study where TVM and CSP has been
compared, and in that study a large "covering" TVM was used which was thereafter withdrawn
from the market. In addition,in most studies, operation techniques, especially with CSP are
not standardized. Therefore, further head-to-head comparisons are needed. The investigators
propose a study comparing efficacy and safety when using the TVM or CSP approach in women
with an apical defect. The investigators will also evaluate whether, in CSP, apical fixation
alone is sufficient, or whether levator plane fixation provide a better outcome.
Study objective:
The main objective of the study is to compare subjective efficacy (PFDI-20, question nro 3;
feeling of bulge) between TVM and CSP in women with an apical prolapse. The CSP group is
further divided into two sub-groups; one where the mesh fixation is only at the apical part
of the vagina, and another where the fixation is also extended to the levator plane.
The secondary outcomes are safety (peri- and post-surgery complications, pain, erosion),
objective efficacy (simplified POP-Q), and re-operation rate. Subjective outcome also
includes the assessment of sexual satisfaction. Cost-effectiveness is studied by comparing
both direct costs and QALYs.
Inclusion criteria:
Age over 18 years and capability to understand the study protocol either in Finnish or
Swedish.
Objectively diagnosed symptomatic apical prolapse (leading apical prolapse (points C/D ≥-2)
and a history of previous POP operation including hysterectomy.
No need for any other concomitant operations except colporrhaphies and possible prophylactic
salpingo-oophorectomy in CSP groups
Exclusion criteria:
A history of previous serious or prolonged pain after any operation. Regular use of systemic
corticosteroid medication. Incapability to understand the study protocol.
Groups, procedures, and randomization:
The participants are randomized into three groups:
1. Transvaginal mesh: BSC mesh (A.M.I., Feldkirch, Austria) is attached to the sacrospinous
ligaments and to the apical part of the vagina. Briefly, 0,25% Lidocain solution with
adrenaline is injected to the anterior vaginal wall and towards the sacrospinous
ligaments bilaterally to reduce bleeding and aid dissection. A vertical incision to the
anterior vaginal wall is done from a point below the bladder neck to approximately 1cm
from the vaginal apex. A full-thickness blunt dissection is done leaving the vaginal
fascia laterally, with tunneling to the sacrospinous ligaments. The two arms of the mesh
are attached with an i-Stich instrument (A.M.I.) to the sacrospinous ligaments 1-2 cm
laterally from the ischial spines. The anterior edge of the mesh is attached to the
vaginal fascia with three Monocryl 3-0 sutures. If needed, the mesh may be shortened in
length and is so, the removed piece is measured and recorded. The arms of the mesh are
set to the stage that the vaginal wall is reduced to its natural position. Complete
vaginal wound closure is done with Vicryl 3-0 sutures. A roll of vaginal gauze for
compression is applied and foley catheter inserted until the following morning. A single
i.v. dose of 1.5g cefuroxime antibiotic is given at the time of anesthesia induction.
2. Colposacropexy with the apical fixation only: PelviGYNious (A.M.I., Feldkirch, Austria)
CSP mesh is attached laparoscopically to the apical part of the vagina. Briefly, a
single i.v. dose 1.5 g of cefuroxime is administered at the time of the anesthesia
induction. The umbilical entry is done optically by a 11 mm trocar and a
pneumoperitoneum up to 12 mmHg is created (then lowered to 8 mmHg, if possible, after
all trocars are inserted). A five mm trocar is placed to the left lower abdomen, a 11 mm
trocar on the left side superior to the previous and a 7.5 mm Airseal trocar to the
right lower abdomen. The promontory is visualized and the avascular space is dissected
by an advanced energy instrument (Thunderbeat, Olympus). The right ureter, the major
vessels and the right hypogastric nerve trunk are identified and avoided during the
dissection. Opening of the right pelvic peritoneum is done with dissection of the
pararectal space. The posterior vaginal peritoneum is opened below the level of the
insertions of the uterosacral ligaments (USL) and the opening is extended to the
peritoneum over the left pararectal area. The rectovaginal and the left pararectal
spaces are dissected to create a posterior peritoneal flap. Anteriorly, the peritoneum
below the vaginal apex is opened and dissected to create an anterior peritoneal flap. A
CSP mesh is fixed to the vaginal apex with five non-absorbable Surgilon 2-0 sutures
utilizing an extracorporeal knot-tying technique: three in a row to the apex and two to
the sides two centimeters posterior to the apex (or alternatively three sutures to the
cervix if it is present). A vaginal speculum examination is performed and any sutures
penetrating the vaginal mucosa are removed and replaced with new ones. The tension of
the mesh is controlled visually via a speculum examination. Anterior and/or posterior
colporraphy is introduced at this point if a vaginal wall prolapse exceeding -2 position
is seen after tensioning the mesh. The mesh is attached to the promontory with five
fasteners (CapSure, Bard). The peritoneum is closed by a running V-Loc™.
3. Colposacropexy with the apical and the levator fixation: PelviGYNious (A.M.I.,
Feldkirch, Austria) CSP mesh is attached laparoscopically to the apical part of the
vagina with fixation reaching to the level of the levator planes. Briefly, the technique
is similar to the apical fixation with the following exceptions: the pararectal spaces
are dissected deep to the level of the levator ani muscles and the CSP mesh is fixed
with 11 sutures (figure) (two to the levator ani muscles, two to the insertions of the
USLs and two to the midline of the posterior vaginal wall; the apical fixation is done
similar to the former group).
In all groups concomitant colporrhaphies can be conducted. Anterior or posterior colporraphy
is done in the following fashion: a 0,25% lidocaine solution containing adrenaline is
injected under the anterior or posterior vaginal wall to provide haemostasis and
hydrodissection. The vaginal wall is incised and the fascia is separated from the vaginal
epithelium using a combination of sharp and blunt dissection. The fascia is plicated using a
running 3-0 PDS suture in two layers. Excess vaginal epithelium is excised and the vaginal
epithelium is closed with a running 3-0 Vicryl suture.
All the operators have conducted at least ten surgeries with the mesh before taking part into
the study.
Power calculation:
The primary outcome is subjective success; defined as the absence of vaginal bulge, i.e.
negative response to PDFI-20, question 3 at one-year following the surgery. Previous
literature show various results. Altman et al (NEJM 2011) described that this outcome was
achieved in 61% of women following a transvaginal mesh surgery. A prospective study by Duraes
et al (2019) and Wei et al described an even higher success of 92% to 94%. Laparoscopic CSP
has shown a subjective success rate of 91% to 94%. Based on these findings we assumed that
the subjective success would be 80% following laparoscopic CSP and 75% following a TVM. The
TVM operation is the study population that is compared to the laparoscopic CSP performed in
two different technique (see methods).
The statistical power is based on a non-inferiority assumption with a binary outcome. On the
basis of previous studies we estimated that 96 patients are needed in each group for 80%
power to detect a 20% difference in the primary outcome measure, with a two-tailed error of
1%.
A drop-out ratio of 10% is assumed and 106 women are needed in each group (transvaginal mesh,
laparoscopic colposacropexy type A and laparoscopic colposarcopexy type B). Thus, a total of
318 women are planned to be randomized for the study.
Subjective outcome:
Symptom spesific: Pelvic floor Distress Inventory (PFDI-20), Pelvic floor Impact
Questionnaire (PFIQ), Pelvic Organ Prolapse / Urinary Incontinence Sexual Questionnaire
(PISQ-12) Overall quality of life: 15D and RAND-36 questionnaires Pain is evaluated by visual
analogue scale (VAS; 0-10) scale. The questionnaires are filled preoperatively, and after 6
months, 12 months, and 5 years.
Objective outcome:
Evaluation of the leading part of the apical point, and anterior and posterior vaginal walls
(cm in relation to the hymen level) preoperatively, and after 6 months, 12 months, and 5
years.
Peri- and postoperative (both short- and long-term) complications and possible re-operations
are recorded and classified according to the Claviend-Dindo.
Operation time, hospital stay, length of sick leave and costs of medications for operation
and possible complications are recorded.
Cost-effectiveness:
Direct and indirect costs cover length of operation time, length of hospital stay, needed
pain medication at home, other needed medication, length of sick leave, costs of possible
further outpatient department visits or hospital stay with possible re-operations.
QALY calculations are based on 15D and RAND-36 questionnaires.
