HALON: Hysterectomy by Transabdominal Laparoscopy or NOTES

• Sponsor: Imelda Hospital, Bonheiden (Other)
• Overall Status: Completed
• CT.gov ID: NCT02631837
• Collaborator: (none)
• Enrollment: 70
• Location: 1
• Arms: 2
• Actual Duration (Months): 19.4
• Patients Per Site Per Month: 3.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Uterine Diseases	Procedure: vNOTES hysterectomy; Procedure: LSC hysterectomy	N/A

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'.

1. 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.

1. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Hysterectomy for Benign Gynaecological Disease by Natural Orifice Transluminal Endoscopic Surgery or Laparoscopy
• Actual Study Start Date: Dec 1, 2015
• Actual Primary Completion Date: Feb 24, 2017
• Actual Study Completion Date: Jul 15, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: vNOTES hysterectomy vaginal Natural Orifice Transluminal Endoscopic Surgery	Procedure: vNOTES hysterectomy; Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy
Active Comparator: LSC hysterectomy Laparoscopic hysterectomy	Procedure: LSC hysterectomy; Surgical removal of the uterus by transabdominal laparoscopy

Outcome Measures

Primary Outcome Measures

1. Successful Removal of the Uterus Without Conversion to Another Technique [Intraoperative]

   Successful removal of the uterus without conversion to another technique with or without morcellation

Secondary Outcome Measures

1. Admission in Hospital for at Least One Night Observation [Measured on the day of the surgical intervention]

   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.

2. Postoperative Pain Scores [The first seven days after the surgical intervention]

   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.

3. The Use of Analgetic Drugs for Postoperative Pain [The first week after the surgical intervention]

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

4. Postoperative Infection [The first six weeks after the surgical intervention]

   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.

5. Intra- Operative Complications [At the time of the surgical intervention]

   Intra- operative complications according to the Clavien- Dindo classification detected during the first six weeks of surgery, as a dichotomous outcome

6. Postoperative Complications [The first six weeks after the surgical intervention]

   Postoperative complications detected during the first six weeks of surgery, as a dichotomous outcome

7. Hospital Readmission [The first six weeks after the surgical intervention]

   The number of women readmitted to hospital within six weeks following surgery, as a dichotomous outcome.

8. Duration of the Surgical Intervention [Intraoperative]

   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

9. Vaginal Pain During Sexual Intercourse at Three Months [At 3 months after the surgical intervention]

   Incidence of vaginal dyspareunia recorded by the participants at 3 months by self-reporting using a simple questionnaire.

10. Vaginal Pain During Sexual Intercourse at Six Months [At 6 months after the surgical intervention]

    Incidence of vaginal dyspareunia recorded by the participants at 6 months by self-reporting using a simple questionnaire

11. Pelvic Pain During Sexual Intercourse at Three Months [At 3 months after the surgical intervention]

    Incidence of pelvic dyspareunia recorded by the participants at 3 months by self-reporting using a simple questionnaire.

12. Pelvic Pain During Sexual Intercourse at Six Months [At 6 months after the surgical intervention]

    Incidence of pelvic dyspareunia recorded by the participants at 6 months by self-reporting using a simple questionnaire.

13. Health-related Quality of Life at Three Months [At 3 months after the surgical intervention]

    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).

14. Health-related Quality of Life at Six Months [At 6 months after the surgical intervention]

    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).

15. Sexual Well Being [At baseline, 3 months and 6 months after the surgical intervention]

    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.

16. Direct Costs [Up to 6 weeks postoperative]

    Calculating the comparative direct costs in USD of both techniques up to 6 weeks after the surgical intervention

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Imelda Hospital	Bonheiden	Antwerp	Belgium	2820

Sponsors and Collaborators

• Imelda Hospital, Bonheiden

Investigators

• Principal Investigator: Jan Baekelandt, MD, Imelda Hospital, Bonheiden

Study Documents (Full-Text)

• Study Protocol - Dec 28, 2015
• Statistical Analysis Plan - Jan 14, 2016

More Information

Publications

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

• Responsible Party: Dr Jan Baekelandt, MD, Dr, Imelda Hospital, Bonheiden
• ClinicalTrials.gov Identifier: NCT02631837
• Other Study ID Numbers: B689201526261
• First Posted: Dec 16, 2015
• Last Update Posted: Dec 14, 2021
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Dr Jan Baekelandt, MD, Dr, Imelda Hospital, Bonheiden: NOTES; Laparoscopic surgery
• Additional relevant MeSH terms: Uterine Diseases

Study Results

Participant Flow

Recruitment Details	Between December 9, 2015, and February 23, 2017, 194 women were screened for eligibility

Arm/Group Title	vNOTES Hysterectomy	LSC Hysterectomy
Arm/Group Description	vaginal Natural Orifice Transluminal Endoscopic Surgery vNOTES hysterectomy: Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy	Laparoscopic hysterectomy LSC hysterectomy: Surgical removal of the uterus by transabdominal laparoscopy
Period Title: Overall Study
STARTED	35	35
COMPLETED	35	35
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	vNOTES Hysterectomy	LSC Hysterectomy	Total
Arm/Group Description	vaginal Natural Orifice Transluminal Endoscopic Surgery vNOTES hysterectomy: Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy	Laparoscopic hysterectomy LSC hysterectomy: Surgical removal of the uterus by transabdominal laparoscopy	Total of all reporting groups
Overall Participants	35	35	70
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	46	49	47
Sex/Gender, Customized (Count of Participants)
Female	35 100%	35 100%	70 100%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Belgium	35 100%	35 100%	70 100%
Body Mass Index (kg/m²) [Mean (Full Range) ]
Mean (Full Range) [kg/m²]	26.6	26.4	26.5
Number of vaginal births (number of vaginal births) [Mean (Full Range) ]
Mean (Full Range) [number of vaginal births]	1.4	1.3	1.4
Prior abdominal surgery (Count of Participants)
Count of Participants [Participants]	20 57.1%	16 45.7%	36 51.4%
Prior Caesarean section (Count of Participants)
Count of Participants [Participants]	8 22.9%	5 14.3%	13 18.6%
Uterine weight (grams) [Mean (Full Range) ]
Mean (Full Range) [grams]	206.2	177.3	191.7
Pain vagina sexual intercourse (Count of Participants)
Count of Participants [Participants]	15 42.9%	6 17.1%	21 30%
Pain abdomen sexual intercourse (Count of Participants)
Count of Participants [Participants]	12 34.3%	8 22.9%	20 28.6%
Health-related quality of life (units on a scale) [Mean (Full Range) ]
Mean (Full Range) [units on a scale]	74.6	76.8	75.7

Outcome Measures

1. Primary Outcome

Title	Successful Removal of the Uterus Without Conversion to Another Technique
Description	Successful removal of the uterus without conversion to another technique with or without morcellation
Time Frame	Intraoperative

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	vNOTES Hysterectomy	LSC Hysterectomy
Arm/Group Description	vaginal Natural Orifice Transluminal Endoscopic Surgery vNOTES hysterectomy: Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy	Laparoscopic hysterectomy LSC hysterectomy: Surgical removal of the uterus by transabdominal laparoscopy
Measure Participants	35	35
Count of Participants [Participants]	35 100%	35 100%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	vNOTES Hysterectomy, LSC Hysterectomy
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Our hypothesis was that women would accept a higher conversion rate of 15% for vNOTESbased on a telephone interview of 10 women treated by total vaginal NOTES hysterectomy. Women were asked to choose among five cut-off rates (5, 10, 15, 20 or 25%). Most women indicated 15%. We would conclude non-inferiority when the upper limit of the one-sided 95% confidence interval for the difference in the proportions of women between both comparisons would be below 15%.
Statistical Test of Hypothesis	p-Value	0.0221
	Comments	The Farrington-Manning test for non-inferiority was performed with 5% significance level and yielded P = 0.0221 in a sensitivity analysis assuming one conversion in the vNOTES and 0 conversions in the laparoscopy group.
	Method	Farrington-Manning
	Comments

2. Secondary Outcome

Title	Admission in Hospital for at Least One Night Observation
Description	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.
Time Frame	Measured on the day of the surgical intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	vNOTES Hysterectomy	LSC Hysterectomy
Arm/Group Description	vaginal Natural Orifice Transluminal Endoscopic Surgery vNOTES hysterectomy: Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy	Laparoscopic hysterectomy LSC hysterectomy: Surgical removal of the uterus by transabdominal laparoscopy
Measure Participants	35	35
Count of Participants [Participants]	8 22.9%	20 57.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	vNOTES Hysterectomy, LSC Hysterectomy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.34
	Confidence Interval	(2-Sided) 95%; -0.56 to -0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Postoperative Pain Scores
Description	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.
Time Frame	The first seven days after the surgical intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	vNOTES Hysterectomy	LSC Hysterectomy
Arm/Group Description	vaginal Natural Orifice Transluminal Endoscopic Surgery vNOTES hysterectomy: Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy	Laparoscopic hysterectomy LSC hysterectomy: Surgical removal of the uterus by transabdominal laparoscopy
Measure Participants	35	35
mean pain VAS score day 1 morning	3.629	4.200
mean pain VAS score day 1 evening	3.486	4.456
mean pain VAS score day 2 morning	2.486	3.543
mean pain VAS score day 2 evening	2.514	3.343
mean pain VAS score day 3 morning	1.800	2.800
mean pain VAS score day 3 evening	1.857	2.914
mean pain VAS score day 4 morning	1.257	2.286
mean pain VAS score day 4 evening	1.371	2.457
mean pain VAS score day 5 morning	1.143	1.914
mean pain VAS score day 5 evening	1.057	2.086
mean pain VAS score day 6 morning	0.914	1.914
mean pain VAS score day 6 evening	1.086	2.000
mean pain VAS score day 7 morning	1.029	1.567
mean pain VAS score day 7 evening	0.819	1.693

4. Secondary Outcome

Title	The Use of Analgetic Drugs for Postoperative Pain
Description	Postoperative pain defined by the total amount of analgesics used as described in the standardized pain treatment protocol, as a continuous outcome.
Time Frame	The first week after the surgical intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	vNOTES Hysterectomy	LSC Hysterectomy
Arm/Group Description	vaginal Natural Orifice Transluminal Endoscopic Surgery vNOTES hysterectomy: Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy	Laparoscopic hysterectomy LSC hysterectomy: Surgical removal of the uterus by transabdominal laparoscopy
Measure Participants	35	35
Mean (Full Range) [number of tablets]	8.0	13.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	vNOTES Hysterectomy, LSC Hysterectomy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	Mann-Whitney U test
	Comments	Two-sided test
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.9
	Confidence Interval	(2-Sided) 95%; -10 to -1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Postoperative Infection
Description	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.
Time Frame	The first six weeks after the surgical intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	vNOTES Hysterectomy	LSC Hysterectomy
Arm/Group Description	vaginal Natural Orifice Transluminal Endoscopic Surgery vNOTES hysterectomy: Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy	Laparoscopic hysterectomy LSC hysterectomy: Surgical removal of the uterus by transabdominal laparoscopy
Measure Participants	35	35
Count of Participants [Participants]	1 2.9%	2 5.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	vNOTES Hysterectomy, LSC Hysterectomy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	Fisher Exact
	Comments

6. Secondary Outcome

Title	Intra- Operative Complications
Description	Intra- operative complications according to the Clavien- Dindo classification detected during the first six weeks of surgery, as a dichotomous outcome
Time Frame	At the time of the surgical intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	vNOTES Hysterectomy	LSC Hysterectomy
Arm/Group Description	vaginal Natural Orifice Transluminal Endoscopic Surgery vNOTES hysterectomy: Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy	Laparoscopic hysterectomy LSC hysterectomy: Surgical removal of the uterus by transabdominal laparoscopy
Measure Participants	35	35
Count of Participants [Participants]	1 2.9%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	vNOTES Hysterectomy, LSC Hysterectomy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	> 0.05
	Comments
	Method	Fisher Exact
	Comments

7. Secondary Outcome

Title	Postoperative Complications
Description	Postoperative complications detected during the first six weeks of surgery, as a dichotomous outcome
Time Frame	The first six weeks after the surgical intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	vNOTES Hysterectomy	LSC Hysterectomy
Arm/Group Description	vaginal Natural Orifice Transluminal Endoscopic Surgery vNOTES hysterectomy: Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy	Laparoscopic hysterectomy LSC hysterectomy: Surgical removal of the uterus by transabdominal laparoscopy
Measure Participants	35	35
Count of Participants [Participants]	3 8.6%	13 37.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	vNOTES Hysterectomy, LSC Hysterectomy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.29
	Confidence Interval	(2-Sided) 95%; -0.47 to -0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Hospital Readmission
Description	The number of women readmitted to hospital within six weeks following surgery, as a dichotomous outcome.
Time Frame	The first six weeks after the surgical intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	vNOTES Hysterectomy	LSC Hysterectomy
Arm/Group Description	vaginal Natural Orifice Transluminal Endoscopic Surgery vNOTES hysterectomy: Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy	Laparoscopic hysterectomy LSC hysterectomy: Surgical removal of the uterus by transabdominal laparoscopy
Measure Participants	35	35
Count of Participants [Participants]	1 2.9%	6 17.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	vNOTES Hysterectomy, LSC Hysterectomy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.106
	Comments
	Method	Fisher Exact
	Comments

9. Secondary Outcome

Title	Duration of the Surgical Intervention
Description	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
Time Frame	Intraoperative

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	vNOTES Hysterectomy	LSC Hysterectomy
Arm/Group Description	vaginal Natural Orifice Transluminal Endoscopic Surgery vNOTES hysterectomy: Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy	Laparoscopic hysterectomy LSC hysterectomy: Surgical removal of the uterus by transabdominal laparoscopy
Measure Participants	35	35
Mean (Full Range) [minutes]	41.1	75.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	vNOTES Hysterectomy, LSC Hysterectomy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.01
	Comments
	Method	Mann-Whitney U test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-34
	Confidence Interval	(2-Sided) 95%; -46 to -22
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Vaginal Pain During Sexual Intercourse at Three Months
Description	Incidence of vaginal dyspareunia recorded by the participants at 3 months by self-reporting using a simple questionnaire.
Time Frame	At 3 months after the surgical intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	vNOTES Hysterectomy	LSC Hysterectomy
Arm/Group Description	vaginal Natural Orifice Transluminal Endoscopic Surgery vNOTES hysterectomy: Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy	Laparoscopic hysterectomy LSC hysterectomy: Surgical removal of the uterus by transabdominal laparoscopy
Measure Participants	35	35
Count of Participants [Participants]	8 22.9%	9 25.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	vNOTES Hysterectomy, LSC Hysterectomy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7604
	Comments	We tested a treatment arm by time interaction to study changes in differences for the outcomes during the follow-up period. In absence of such an interaction (p>0.05 for the interaction term), the main effect of treatment was tested.
	Method	Arm by time interaction
	Comments

11. Secondary Outcome

Title	Vaginal Pain During Sexual Intercourse at Six Months
Description	Incidence of vaginal dyspareunia recorded by the participants at 6 months by self-reporting using a simple questionnaire
Time Frame	At 6 months after the surgical intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	vNOTES Hysterectomy	LSC Hysterectomy
Arm/Group Description	vaginal Natural Orifice Transluminal Endoscopic Surgery vNOTES hysterectomy: Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy	Laparoscopic hysterectomy LSC hysterectomy: Surgical removal of the uterus by transabdominal laparoscopy
Measure Participants	35	35
Count of Participants [Participants]	5 14.3%	8 22.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	vNOTES Hysterectomy, LSC Hysterectomy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3071
	Comments	We tested a treatment arm by time interaction to study changes in differences for the outcomes during the follow-up period. In absence of such an interaction (p>0.05 for the interaction term), the main effect of treatment was tested.
	Method	Arm by time interaction
	Comments

12. Secondary Outcome

Title	Pelvic Pain During Sexual Intercourse at Three Months
Description	Incidence of pelvic dyspareunia recorded by the participants at 3 months by self-reporting using a simple questionnaire.
Time Frame	At 3 months after the surgical intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	vNOTES Hysterectomy	LSC Hysterectomy
Arm/Group Description	vaginal Natural Orifice Transluminal Endoscopic Surgery vNOTES hysterectomy: Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy	Laparoscopic hysterectomy LSC hysterectomy: Surgical removal of the uterus by transabdominal laparoscopy
Measure Participants	35	35
Count of Participants [Participants]	6 17.1%	8 22.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	vNOTES Hysterectomy, LSC Hysterectomy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4541
	Comments	We tested a treatment arm by time interaction to study changes in differences for the outcomes during the follow-up period. In absence of such an interaction (p>0.05 for the interaction term), the main effect of treatment was tested.
	Method	Arm by time interaction
	Comments

13. Secondary Outcome

Title	Pelvic Pain During Sexual Intercourse at Six Months
Description	Incidence of pelvic dyspareunia recorded by the participants at 6 months by self-reporting using a simple questionnaire.
Time Frame	At 6 months after the surgical intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	vNOTES Hysterectomy	LSC Hysterectomy
Arm/Group Description	vaginal Natural Orifice Transluminal Endoscopic Surgery vNOTES hysterectomy: Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy	Laparoscopic hysterectomy LSC hysterectomy: Surgical removal of the uterus by transabdominal laparoscopy
Measure Participants	35	35
Count of Participants [Participants]	4 11.4%	5 14.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	vNOTES Hysterectomy, LSC Hysterectomy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4514
	Comments	We tested a treatment arm by time interaction to study changes in differences for the outcomes during the follow-up period. In absence of such an interaction (p>0.05 for the interaction term), the main effect of treatment was tested.
	Method	Arm by time interaction
	Comments

14. Secondary Outcome

Title	Health-related Quality of Life at Three Months
Description	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).
Time Frame	At 3 months after the surgical intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	vNOTES Hysterectomy	LSC Hysterectomy
Arm/Group Description	vaginal Natural Orifice Transluminal Endoscopic Surgery vNOTES hysterectomy: Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy	Laparoscopic hysterectomy LSC hysterectomy: Surgical removal of the uterus by transabdominal laparoscopy
Measure Participants	35	35
Mean (Full Range) [score on a scale]	83.8	79.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	vNOTES Hysterectomy, LSC Hysterectomy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3473
	Comments	We tested a treatment arm by time interaction to study changes in differences for the outcomes during the follow-up period. In absence of such an interaction (p>0.05 for the interaction term), the main effect of treatment was tested.
	Method	Arm by time interaction
	Comments

15. Secondary Outcome

Title	Health-related Quality of Life at Six Months
Description	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).
Time Frame	At 6 months after the surgical intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	vNOTES Hysterectomy	LSC Hysterectomy
Arm/Group Description	vaginal Natural Orifice Transluminal Endoscopic Surgery vNOTES hysterectomy: Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy	Laparoscopic hysterectomy LSC hysterectomy: Surgical removal of the uterus by transabdominal laparoscopy
Measure Participants	35	35
Mean (Full Range) [score on a scale]	87.8	86.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	vNOTES Hysterectomy, LSC Hysterectomy
	Comments
	Type of Statistical Test	Superiority
	Comments	We tested a treatment arm by time interaction to study changes in differences for the outcomes during the follow-up period. In absence of such an interaction (p>0.05 for the interaction term), the main effect of treatment was tested.
Statistical Test of Hypothesis	p-Value	0.3473
	Comments	We tested a treatment arm by time interaction to study changes in differences for the outcomes during the follow-up period. In absence of such an interaction (p>0.05 for the interaction term), the main effect of treatment was tested.
	Method	Arm by time interaction
	Comments

16. Secondary Outcome

Title	Sexual Well Being
Description	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.
Time Frame	At baseline, 3 months and 6 months after the surgical intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

17. Secondary Outcome

Title	Direct Costs
Description	Calculating the comparative direct costs in USD of both techniques up to 6 weeks after the surgical intervention
Time Frame	Up to 6 weeks postoperative

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	vNOTES Hysterectomy	LSC Hysterectomy
Arm/Group Description	vaginal Natural Orifice Transluminal Endoscopic Surgery vNOTES hysterectomy: Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy	Laparoscopic hysterectomy LSC hysterectomy: Surgical removal of the uterus by transabdominal laparoscopy
Measure Participants	35	35
Mean (Full Range) [USD]	3452.2	3933.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	vNOTES Hysterectomy, LSC Hysterectomy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.110
	Comments
	Method	Mann-Whitney U test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-555.8
	Confidence Interval	(2-Sided) 95%; -1,044 to 36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	Intra- or postoperative complications
Arm/Group Title	vNOTES Hysterectomy		LSC Hysterectomy
Arm/Group Description	vaginal Natural Orifice Transluminal Endoscopic Surgery vNOTES hysterectomy: Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy		Laparoscopic hysterectomy LSC hysterectomy: Surgical removal of the uterus by transabdominal laparoscopy
All Cause Mortality
	vNOTES Hysterectomy		LSC Hysterectomy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/35 (0%)
Serious Adverse Events
	vNOTES Hysterectomy		LSC Hysterectomy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		2/35 (5.7%)
Renal and urinary disorders
vesicovaginal fistula	0/35 (0%)	0	1/35 (2.9%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolus	0/35 (0%)	0	1/35 (2.9%)	1
Other (Not Including Serious) Adverse Events
	vNOTES Hysterectomy		LSC Hysterectomy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/35 (8.6%)		11/35 (31.4%)
Blood and lymphatic system disorders
Blood transfusion	1/35 (2.9%)	1	2/35 (5.7%)	2
Renal and urinary disorders
Urinary tract infection	2/35 (5.7%)	2	9/35 (25.7%)	9

Limitations/Caveats

Data on postoperative pain scores are available in figure 2 in Baekelandt JF, et al. BJOG 2019;126:105-113. Dat on sexual well-being will be analysed at a later date.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.