Vaginal NOTES Hysterectomy Versus Vaginal Hysterectomy

Study Overview
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Brief Summary
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Rationale: Natural orifice transluminal endoscopic surgery (NOTES) is a minimal invasive technique using the natural body orifices like stomach, oesophagus, bladder, rectum and vagina to access the human body for surgery. In 2012, the first vaginal NOTES (vNOTES) hysterectomy was performed. Potential benefits of vNOTES hysterectomy, also called the vaginal assisted NOTES hysterectomy (VANH) are no visible scars, less pain and a shorter hospital stay compared with laparoscopic hysterectomy as shown in the HALON trial. Up to now, no studies have compared the vNOTES hysterectomy with vaginal hysterectomy. Objective: The aim of this study is to compare the vNOTES hysterectomy with the vaginal hysterectomy for same day-discharge (SDD), complications, treatment related outcomes, post-operative recovery, quality of life and cost-effectiveness. Study design: The study concerns a single-blinded, multicentre, randomised controlled trial. Study population: Eligible women who fulfill the inclusion criteria and will undergo a hysterectomy for benign indication. Intervention: The study population will be randomly allocated to the VANH-group, who undergo a vaginal assisted NOTES hysterectomy (intervention group) or the vaginal hysterectomy group (control-group) and the participants will be single blinded. The pre- and postoperative care will be the same for both groups. Main study parameters/endpoints: Primary outcome is the percentage of patients that underwent the hysterectomy as in SDD setting. A total of 41 patients should be included in the control group and a total of 83 patients in the intervention group, using an enrollment ratio of 1:2, with an alpha of 0.05 and a power of 0.8. The secondary outcomes are complications, treatment related outcomes, post-operative recovery, quality of life and cost-effectiveness. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: vNOTES is a new surgical technique, but a combination of two existing techniques namely the vaginal hysterectomy and the laparoscopic hysterectomy. Only one randomized controlled trial has been published, comparing the total laparoscopic hysterectomy (TLH) with the VANH, which shows no inferiority of the vNOTES technique compared to a laparoscopy. A recent case series study has been published about the complication rate in VANH. There was a total complication rate in the hysterectomy group of 5.2%, in which 1.4% was intra-operative and 3.8% postoperative. Theoretically it is possible that the VANH causes less intra-operative complications because of an improved view during the procedure. No further literature is known about VH versus VANH. Participants of the study should fill in multiple questionnaires before randomization and postoperative about their general health, pain experience and used analgesics.

Detailed Description
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The hysterectomy is one of the most performed gynaecological surgeries worldwide. In the Netherlands about 14.500 hysterectomies are performed yearly. The most common benign indications to perform a hysterectomy are abnormal uterine bleeding, uterine leiomyomas, endometriosis or adenomyosis, chronic pelvic pain, uterine prolapse, benign ovarian neoplasm, hyperplasia or atypia of the endometrium or cervical dysplasia. The four approaches to perform a hysterectomy for benign disease are abdominal hysterectomy (AH), vaginal hysterectomy (VH), (total) laparoscopic hysterectomy ((T)LH) and robotic-assisted hysterectomy (RH). VH appears to be superior to the AH, resulting in a quicker recovery. The LH results in a quicker recovery than the AH and VH, but increases the risks of damage to the bladder or ureter. That is why a recent Cochrane review advises to perform a VH when feasible for women undergoing a hysterectomy for a benign indication. When VH is technically not feasible, a LH or AH is performed. LH resulted in more rapid recovery, fewer febrile episodes and less wound complications compared to AH. The RH is not superior compared to the LH and is associated with higher costs. Since the introduction of laparoscopy, the VH and AH decreased and the rate of LH significantly increased between 2002 and 2012. Performing a LH gives the opportunity to inspect the abdominal cavity and to easily perform an opportunistic salpingectomy compared to VH. An opportunistic salpingectomy during a hysterectomy for benign indication might reduce the overall risk of ovarian cancer. Additionally, patients experience less postoperative pain after a LH compared to a VH and therefore need less post-operative pain medication. Advantages of the VH compared to the LH are a shorter operation duration, no visible scars and a lower chance of dehiscence of the vaginal cuff. In 2004, a novel approach of endoscopic surgery was described, 'Natural Orifice Transluminal Endoscopic Surgery (NOTES) by researchers at the John Hopkins University. It is a surgical technique using natural orifices of the body (e.g. mouth, anus, urethra, vagina) to perform scarless surgery. The vaginal approach is called the vNOTES technique. NOTES is an emerging field within minimal access surgery, evolves and presents multiple possibilities for innovation and development. The initial approach was trans gastric, but subsequently, NOTES has been evolved, resulting in trans rectal, trans gastric, transvaginal, and transurethral approaches nowadays. In 2012, the first vNOTES hysterectomy, also called vaginal assisted NOTES hysterectomy (VANH) was performed. vNOTES surgery can be used for different indications, for example hysterectomy, adnexectomy or salpingectomy in case of an ectopic pregnancy. In 2018, the first randomised controlled trial (RCT) comparing TLH with VANH in 70 women was published. This HALON trial showed VANH was non-inferior to TLH. Compared to TLH, surgery time was significantly shorter, patients experience less post-operative pain and same day discharge (SDD) was possible in 77% of the women who underwent the VANH compared to 43% after TLH. Besides, the VANH showed less post-operative complications. Except for the HALON trial and two retrospective studies and case-control studies, there is little literature about VANH. No studies have been performed comparing the VH with the VANH. Because the VH is the preferred method to perform a hysterectomy for a benign indication, there is a need to compare VH with VANH and to explore the indications to perform a VANH. The aim of this study is to compare the VANH with the VH for same day discharge (SDD), complications, treatment related outcomes, post-operative recovery, quality of life and cost-effectiveness. We hypothesize that patients who underwent a VANH procedure are more often able to be treated in SDD setting.

Official Title
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Vaginal Hysterectomy Versus Vaginal Assisted NOTES Hysterectomy (VANH): a Randomised Controlled Trial

Conditions
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Hysterectomy, Natural Orifice Transluminal Endoscopic Surgery, Vaginal Hysterectomy

Intervention / Treatment
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* Procedure: Vaginal NOTES hysterectomy
* Procedure: Vaginal hysterectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written and orally given informed consent 18 years and older Native Dutch speaker or in control of the Dutch language in speaking and writing Indication for hysterectomy for benign indication Possible to perform a VH judged by experienced (resident) gynaecologist during gynaecological examination Exclusion Criteria: Any contra-indication for VH (for example, large uterus myomatosus, not enough descensus, etc) as judged by experienced gynaecologist History of more than 1 caesarean section History of endometriosis History of rectal surgery History of pelvic radiation Suspected rectovaginal endometriosis History of pelvic inflammatory disease, especially prior tubo-ovarian or pouch of Douglas abscess or suspected adhesions due to (ruptured) inflammatory disease (for example ruptured appendicitis) Virginity Pregnancy Indication for anterior or posterior colporrhaphy during the same surgery Indication of mid urethral slings Uterus myomatosus will not be an exclusion criteria but the surgeon will indicate if it is possible to remove the uterus vaginally.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single-blinded, multicentre, randomised controlled trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VANH hysterectomy<br>Access to the peritoneal cavity will be performed similar to vaginal surgery by a circular incision around the cervix, anterior and posterior colpotomy and transsecting the sacro-uterine ligaments. The vNOTES port will be placed to get access to the abdominal cavity and a pneumoperitoneum will be created. After positioning in 20o degree Trendelenburg laparoscopic instruments will be introduced. The peritoneal cavity and ureters are inspected. The hysterectomy is performed by dissecting from caudally to cranially. The fallopian tubes will be removed elective after counselling in the outpatient clinic and the ovaries will be removed on indication only. Haemostasis is checked and the vNOTES port and the uterus are removed trans-vaginally and the pneumoperitoneum is deflated. The vaginal cuff will be closed using a running Vicryl-1 suture. The urinary bladder catheter will be removed directly postoperative. | Procedure: Vaginal NOTES hysterectomy<br>* Vaginal assited NOTES hysterectomy<br>|
| Active Comparator: Vaginal hysterectomy<br>A circumferential incision is made around the cervix. Access to the peritoneal cavity will be performed through anterior and posterior colpotomy. The sacro-uterine ligaments, ligamenta cardinalia uterine arteries will be clamped and dissected. Finally, the ovarian ligament, round ligament and fallopian tubes will be dissected and tied. The uterus will be removed and the vagina will be closed. The urinary bladder catheter will be removed directly postoperative. | Procedure: Vaginal hysterectomy<br>* Vaginal hysterectomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of same day discharge | Same day discharge | First 24hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complications | Severity scored by Clavien Dindo classifications | Week 6 after surgery | 
| Treatment related outcomes-1 | Conversion | During surgery | 
| Intended number of salphingectomies in each group | Intended number of salphingectomies | During surgery | 
| Performed number of salphingectomies in each group | Performed number of salphingectomies | During surgery | 
| Recovery Index-10 (RI-10) pre- and postoperative | Recovery Index-10 (RI-10) | Week 12 after surgery | 
| Health- related Quality of LIfe (EQ-5D-5L questionnaire) | EQ-5D-5L questionnaire | Week 12 after surgery | 
| Costs | Intervention costs, hospital costs, health care costs outside the hospital (using iMCQ questionnaire) | Week 12 after sugery | 
| Cost effectiveness | Cost effectiveness between vaginal NOTES hysterectomy versus vaginal hysterectomy comparing the costs as mentioned at outcome 8 | Week 12 after surgery | 
| Treatment related outcomes-2 | Time in operating theatre in minutes | During surgery | 
| Treatment related outcomes- 3 | Surgery time in minutes | During surgery | 
| Treatment related outcomes -4 | blood loss in mL | During surgery | 
| Treatment related outcomes -5 | Pain after surgery measured on numeric rating scale | First 24 hours after surgery | 
| Treatment related outcomes -6 | Recovery of pain in first 7 days after surgery measured on numeric rating scale | Day 7 after surgery | 
| Treatment related outcomes - 7 | Use of analgesics | Day 7 after surgery | 
| Treatment related outcomes - 8 | resumption of daily activity | Week 6 after surgery | 
| Treatment related outcomes - 9 | hospital re-admission | Week 6 after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NOTES surgery, vNOTES, VANH, Vaginal hysterectomy, Hysterectomy