Hysterectomy by Transabdominal Laparoscopy or NOTES

Uterine Diseases Clinical Trial

— HALON  

Official title:

Hysterectomy for Benign Gynaecological Disease by Natural Orifice Transluminal Endoscopic Surgery or Laparoscopy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02631837
• Other study ID #: B689201526261
• Status: Completed
• Phase: N/A
• Start date: December 2015
• Est. completion date: July 15, 2017

Study information

• Verified date: March 2023
• Source: Imelda Hospital, Bonheiden
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Objective: To randomly compare hysterectomy by vaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) versus laparoscopy uterus in women with benign gynecological pathology.

Study design: Randomized controlled/single center/single-blinded/parallel-group/non-inferiority/efficacy trial.

Study population: All women aged 18 to 70 years regardless of parity with a non-prolapsed uterus and a benign indication for hysterectomy.

Primary study outcome parameters: successful removal of the uterus by the intended technique.

Secondary outcomes: the proportion of women admitted to the in-hospital ward; postoperative pain scores; the total amount of analgesics used; postoperative infection; per- or postoperative complications; hospital readmission rates; duration of the surgical procedure; incidence and intensity of dyspareunia; sexual wellbeing; health-related quality of life; costs.

Description:

l1.Objectives of the HALON Trial The primary research questions of this IDEAL stage 2b efficacy trial are as follows: is a vNOTES (vaginal Natural Orifice Transluminal Endoscopic Surgery) hysterectomy at least as effective compared to the standard transabdominal laparoscopic approach (LSC) for removing a non-prolapsed uterus without the need for conversion to an alternative approach? (non inferiority design)

Secondary research questions are:

• Do more women treated by vNOTES prefer to leave the day care unit on the day of surgery compared to LSC?

• Do women treated by vNOTES suffer from less pain compared to women treated by LSC in the first postoperative week?

• Is the removal of a uterus by vNOTES faster compared to LSC?

• Does a vNOTES cause more pelvic infection or other complications compared to LSC?

• Does a vNOTES result in more hospital readmissions within 6 weeks after surgery compared to LSC?

• Does a vNOTES approach result in more women reporting dyspareunia, less sexual wellbeing or less health-related quality of life at 3 or 6 months after surgery when compared to women treated by LSC?

• What are the direct and indirect costs up to 6 weeks after the surgical intervention of a vNOTES compared to LSC? 2. TRIAL DESIGN 2.1. Design A single center, single-blinded, parallel group randomized, non-inferiority efficacy trial.

2.2. Simple pilot randomized trial. 2.3. Time schedule Based upon the mean number of hysterectomies performed annually for benign gynecological disease at the department of Obstetrics and Gynecology of the participating center (168) the investigators estimate that the duration of recruitment will be 12 months. Based upon the follow up (6 months) and the period of analysis/reporting (3 months) the total study period will be 2 years.

2.4. Participating center Department of Obstetrics and Gynecology Imeldahospital Imeldalaan 9 2820 Bonheiden Belgium 3. ELIGIBILITY, CONSENT AND RANDOMIZATION 3.1. Screening and consent prior to surgery All women aged 18 to 70 years, regardless of parity, with a non-prolapsed uterus in need of a hysterectomy for benign indication are eligible for inclusion.

3.2. Determining eligibility All women aged 18 to 70 years, regardless of parity, with a non-prolapsed uterus in need of a hysterectomy for benign indication who provide consent to participation are eligible in the HALON trial and will be randomized before the procedure.

3.3. Randomization If the woman is eligible for the HALON trial, the trial secretary will obtain a randomized allocation the day before surgery. This will be done using a randomization list generated by a free computer software program offered by Research Randomizer (https://www.randomizer.org). The random sequence generation will be concealed using sequentially numbered opaque sealed envelopes. The envelope will be opened by the nurse assistant the day before surgery for practical logistic reasons.

3.4. Patients with strong preference for treatment A minority of women will express a clear preference for one of both treatments (e.g. strong desire to have no scar) and for this reason will not wish to be randomized between surgical treatments. To investigate how outcomes vary by choice, these women could be followed up in exactly the same way as for those women randomized into the HALON trial. A formal non-randomized follow-up of these women will not be done for logistical reasons.

3.5. Stratification of randomization A blocked randomization procedure will be used to avoid chance imbalances for the parameter 'uterine size'.

4. TREATMENT ALLOCATIONS 4.1. Surgical procedures The principal investigator, who has training and experience in both laparoscopy and NOTES, will perform all surgical procedures. He is therefore not blinded. All vNOTES participants will be blinded by three superficial non-therapeutic or "mock" skin incisions similar to those done with the laparoscopic technique.

4.1.1 vNOTES hysterectomy This is the surgical procedure done in the intervention arm of the HALON trial. 4.1.2 LSC hysterectomy This is the surgical procedure done in the control arm of the HALON trial. 5. FOLLOW-UP AND OUTCOME MEASURES 5.1. Clinical assessments 5.1.1 Format PROMs (Patient reported outcomes) will be collected using a postal questionnaire, which will include a combination of disease specific (Pain on sexual intercourse measured by VAS scale and SSFS Scale) and generic measurement instruments (EQ-5D).

The postal questionnaires will be sent from the HALON Trial Office with postage paid envelopes two weeks before the due date. Reminders will be sent to patients if the questionnaire is not returned within one week of the due date and attempts will be made to contact the patient by phone if the questionnaire is not returned by two weeks after the due date.

5.1.2 Timing of assessments The primary outcome will be measured clinically at the end of the surgical procedure. In addition PROMs will take place at baseline (pain on sexual intercourse, health-related quality of life and sexual well being), the evening of the surgical intervention (in-hospital admission), during the first postoperative week (pain by VAS scores and analgetic drugs) and at 3 and 6 months (dyspareunia/ sexual well being/health related quality of life). Clinical physician assessment will take place the evening of the surgical intervention (in-hospital admission) and during the first six weeks following surgery (pelvic infection, surgical complications, hospital readmission rate).

5.2. Primary clinical outcome measure The proportion of women successfully treated by removing the uterus by the intended approach without conversion to another approach, using a dichotomous outcome measure, will be used as a measure of efficacy.

5.3. Secondary clinical outcome measures

The following secondary outcomes will be measured:

• The proportion of women addmitted in-hospital for at least one night observation based on their own preference, as a dichotomous outcome.

• Postoperative pain scores, as an ordinal outcome, measured using a Visual Analogue Scale (VAS) twice daily from day 1 till 7 self-reported by the participating women. The VAS scores range from 0= no pain to 10= worst imaginable pain.

• Postoperative pain defined by the total amount of analgesics used as described in the standardized pain treatment protocol, as a continuous outcome.

• Postoperative infection as a dichotomous outcome.

• Per- or postoperative complications according to the Clavien- Dindo classification detected during the first six weeks of surgery, as a dichotomous outcome.

• The number of women readmitted to hospital within 6 weeks following surgery.

• Incidence and intensity of dyspareunia recorded by the participants at baseline, 3 and 6 months by self-reporting using a simple questionnaire and a Visual Analogue Scale (VAS) scale, as a dichotomous and ordinal outcome. The VAS scores range from 0= no pain to 10= worst imaginable pain.

• Sexual wellbeing at baseline, at 3 and 6 months by self-reporting the Short Sexual Functioning Scale (SSFS). The SSFS is a questionnaire with 7 multiple choice open ended questions.

• Health related quality of life, at baseline, at 3 and 6 months by self-reporting the EQ-5D-3L scale. The EQ-5D-3L scale is a questionnaire on 5 domains with 3 open ended questions and a scale from 0= worst possible health-related quality of life to 100= best possible health-related quality of life.

• Duration of surgery measured as the time in minutes from the insertion of the bladder catheter to the end of vaginal/abdominal wound closure, as a continuous outcome. 5.4.The direct and indirect costs up to 6 weeks after the hysterectomy of the vNOTES technique compared to LSC.

6. ACCRUAL AND ANALYSIS 6.1. Sample size The sample size for the primary outcome of this trial has been chosen to give good statistical power to preclude any clinically important inferiority of vNOTES compared to laparoscopy and is based on evidence retrieved from a Dutch prospective cohort study. Based on the power calculations for the primary outcome and assuming a loss-to-follow-up rate of 15% we decided to include 66 study participants in the HALON trial.

6.2. Projected accrual and attrition rates Based upon the mean number of hysterectomies performed annually at the department of Obstetrics and Gynecology of the participating center (168) the investigators anticipate that the duration of recruitment will be 12 months. Based upon the follow up (6 months) and the period of analysis/reporting (3 months) the total study period will be 2 years. First publication will be possible within four years of trial commencement.

The sample size calculations have allowed for a 15% loss to follow up rate. In order to minimize rates of attrition a dedicated research secretary will be employed to optimize recruitment and follow up.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: July 15, 2017
• Est. primary completion date: February 24, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• All women aged 18 to 70 years regardless of parity, with a non-prolapsed uterus in need of a hysterectomy for benign indication

• Written informed consent obtained prior to surgery

Exclusion Criteria:

• History of rectal surgery

• Suspected rectovaginal endometriosis

• Suspected malignancy

• History of pelvic inflammatory disease, especially prior tubo-ovarian or pouch of Douglas abscess

• Active lower genital tract infection e.g. Chlamydia, N. gonorrhoeae

• Virgo

• Pregnancy

• Failure to provide written informed consent prior to surgery

Related Conditions & MeSH terms

• Uterine Diseases

Intervention

Procedure:
• vNOTES hysterectomy
Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy
• LSC hysterectomy
Surgical removal of the uterus by transabdominal laparoscopy

Locations

Country	Name	City	State
Belgium	Imelda Hospital	Bonheiden	Antwerp

Sponsors (1)

Lead Sponsor	Collaborator
Imelda Hospital, Bonheiden

Country where clinical trial is conducted

Belgium, 

References & Publications (10)

Atallah S, Martin-Perez B, Albert M, Schoonyoung H, Quinteros F, Hunter L, Larach S. Vaginal Access Minimally Invasive Surgery (VAMIS): A New Approach to Hysterectomy. Surg Innov. 2015 Aug;22(4):344-7. doi: 10.1177/1553350614560273. Epub 2014 Nov 27. — View Citation

Baekelandt J, De Mulder PA, Le Roy I, Mathieu C, Laenen A, Enzlin P, Weyers S, Mol BW, Bosteels JJ. HALON-hysterectomy by transabdominal laparoscopy or natural orifice transluminal endoscopic surgery: a randomised controlled trial (study protocol). BMJ Open. 2016 Aug 12;6(8):e011546. doi: 10.1136/bmjopen-2016-011546. — View Citation

Baekelandt J. Total Vaginal NOTES Hysterectomy: A New Approach to Hysterectomy. J Minim Invasive Gynecol. 2015 Sep-Oct;22(6):1088-94. doi: 10.1016/j.jmig.2015.05.015. Epub 2015 May 22. — View Citation

Baekelandt JF, De Mulder PA, Le Roy I, Mathieu C, Laenen A, Enzlin P, Weyers S, Mol B, Bosteels J. Hysterectomy by transvaginal natural orifice transluminal endoscopic surgery versus laparoscopy as a day-care procedure: a randomised controlled trial. BJOG. 2019 Jan;126(1):105-113. doi: 10.1111/1471-0528.15504. — View Citation

Lee CL, Wu KY, Su H, Wu PJ, Han CM, Yen CF. Hysterectomy by transvaginal natural orifice transluminal endoscopic surgery (NOTES): a series of 137 patients. J Minim Invasive Gynecol. 2014 Sep-Oct;21(5):818-24. doi: 10.1016/j.jmig.2014.03.011. Epub 2014 Mar — View Citation

Reynders A, Baekelandt J. Adnexectomy by Poor Man's Transvaginal NOTES. Gynecol Surg 2015; 12: 207-11

Su H, Yen CF, Wu KY, Han CM, Lee CL. Hysterectomy via transvaginal natural orifice transluminal endoscopic surgery (NOTES): feasibility of an innovative approach. Taiwan J Obstet Gynecol. 2012 Jun;51(2):217-21. doi: 10.1016/j.tjog.2012.04.009. — View Citation

Van Peer S, Baekelandt J. Natural orifice transluminal endoscopic surgery (NOTES) salpingectomy for ectopic pregnancy: a first series demonstrating how a new surgical technique can be applied in a low-resource setting. Gynecol Surg 2015; 12: 299-302

Wang CJ, Huang HY, Huang CY, Su H. Hysterectomy via transvaginal natural orifice transluminal endoscopic surgery for nonprolapsed uteri. Surg Endosc. 2015 Jan;29(1):100-7. doi: 10.1007/s00464-014-3639-y. Epub 2014 Oct 1. — View Citation

Yang YS, Kim SY, Hur MH, Oh KY. Natural orifice transluminal endoscopic surgery-assisted versus single-port laparoscopic-assisted vaginal hysterectomy: a case-matched study. J Minim Invasive Gynecol. 2014 Jul-Aug;21(4):624-31. doi: 10.1016/j.jmig.2014.01. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Successful Removal of the Uterus Without Conversion to Another Technique	Successful removal of the uterus without conversion to another technique with or without morcellation	Intraoperative
Secondary	Admission in Hospital for at Least One Night Observation	The number of women admitted in-hospital for at least one night observation based on their own preference after discharge from the day care unit, as a dichotomous outcome. The decision to discharge or to admit to hospital for the night will be based solely on the choice of the woman to return home the same day or stay overnight.	Measured on the day of the surgical intervention
Secondary	Postoperative Pain Scores	Postoperative pain scores, as an ordinal outcome, measured using a Visual Analogue Scale (VAS) twice daily (morning and evening) from day 1 till 7 selfreported by the participating women. VAS scores from 0 to 10 with 0 = no pain and 10= worst pain ever imaginable.	The first seven days after the surgical intervention
Secondary	The Use of Analgetic Drugs for Postoperative Pain	Postoperative pain defined by the total amount of analgesics used as described in the standardized pain treatment protocol, as a continuous outcome.	The first week after the surgical intervention
Secondary	Postoperative Infection	Postoperative infection defined by lower abdominal pain with fever > 38°C and positive clinical signs or laboratory findings, detected during the first six weeks of surgery, as a dichotomous outcome.	The first six weeks after the surgical intervention
Secondary	Intra- Operative Complications	Intra- operative complications according to the Clavien- Dindo classification detected during the first six weeks of surgery, as a dichotomous outcome	At the time of the surgical intervention
Secondary	Postoperative Complications	Postoperative complications detected during the first six weeks of surgery, as a dichotomous outcome	The first six weeks after the surgical intervention
Secondary	Hospital Readmission	The number of women readmitted to hospital within six weeks following surgery, as a dichotomous outcome.	The first six weeks after the surgical intervention
Secondary	Duration of the Surgical Intervention	Duration of surgery measured as the time in minutes from the insertion of the bladder catheter to the end of vaginal/ abdominal wound closure, as a continuous outcome	Intraoperative
Secondary	Vaginal Pain During Sexual Intercourse at Three Months	Incidence of vaginal dyspareunia recorded by the participants at 3 months by self-reporting using a simple questionnaire.	At 3 months after the surgical intervention
Secondary	Vaginal Pain During Sexual Intercourse at Six Months	Incidence of vaginal dyspareunia recorded by the participants at 6 months by self-reporting using a simple questionnaire	At 6 months after the surgical intervention
Secondary	Pelvic Pain During Sexual Intercourse at Three Months	Incidence of pelvic dyspareunia recorded by the participants at 3 months by self-reporting using a simple questionnaire.	At 3 months after the surgical intervention
Secondary	Pelvic Pain During Sexual Intercourse at Six Months	Incidence of pelvic dyspareunia recorded by the participants at 6 months by self-reporting using a simple questionnaire.	At 6 months after the surgical intervention
Secondary	Health-related Quality of Life at Three Months	Health-related quality of life at 3 months by self-reporting the EQ-5D scale.The reported values for the health-related quality of life are self-reported values using the VAS part of the two part EQ-5D-3L questionnaire. The scale ranges from 0 (worst quality) to 100 (best quality).	At 3 months after the surgical intervention
Secondary	Health-related Quality of Life at Six Months	Health-related quality of life at 6 months by self-reporting the EQ-5D scale. The reported values for the health-related quality of life are self-reported values using the VAS part of the two part EQ-5D-3L questionnaire. The scale ranges from 0 (worst quality) to 100 (best quality).	At 6 months after the surgical intervention
Secondary	Sexual Well Being	Sexual wellbeing at baseline, at 3 and 6 months by self-reporting using the SSFS (Short Sexual Function Scale). The SSFS is a questionnaire of 7 open ended questions on sexual wellbeing.	At baseline, 3 months and 6 months after the surgical intervention
Secondary	Direct Costs	Calculating the comparative direct costs in USD of both techniques up to 6 weeks after the surgical intervention	Up to 6 weeks postoperative