Hysterectomy by Transabdominal Laparoscopy or NOTES

NCT ID: NCT02631837

Last Updated: 2023-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2017-07-15

Brief 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.

Detailed 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.

Conditions

Uterine Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

vNOTES hysterectomy

vaginal Natural Orifice Transluminal Endoscopic Surgery

Group Type: EXPERIMENTAL

vNOTES hysterectomy

Intervention Type: PROCEDURE

Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy

LSC hysterectomy

Laparoscopic hysterectomy

Group Type: ACTIVE_COMPARATOR

LSC hysterectomy

Intervention Type: PROCEDURE

Surgical removal of the uterus by transabdominal laparoscopy

Interventions

vNOTES hysterectomy

Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy

Intervention Type: PROCEDURE

LSC hysterectomy

Surgical removal of the uterus by transabdominal laparoscopy

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Imelda Hospital, Bonheiden

OTHER

Sponsor Role: lead

Responsible Party

Dr Jan Baekelandt, MD

Dr

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jan Baekelandt, MD

Role: PRINCIPAL_INVESTIGATOR

Imelda Hospital, Bonheiden

Locations

Imelda Hospital

Bonheiden, Antwerp, Belgium

Countries

Belgium

References

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

Reference Type: BACKGROUND

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

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

PMID: 27519922 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30325565 (View on PubMed)

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.

Reference Type: RESULT

PMID: 22795097 (View on PubMed)

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 25.

Reference Type: RESULT

PMID: 24681063 (View on PubMed)

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.

Reference Type: RESULT

PMID: 25432882 (View on PubMed)

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.2014.01.005. Epub 2014 Jan 21.

Reference Type: RESULT

PMID: 24462594 (View on PubMed)

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.

Reference Type: RESULT

PMID: 25270610 (View on PubMed)

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.

Reference Type: RESULT

PMID: 26009278 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

B689201526261

Identifier Type: -

Identifier Source: org_study_id