Hysterectomy by Transabdominal Laparoscopy or NOTES
Condition: Uterine Diseases
MeSH terms: Uterine Diseases
Study type: Interventional

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.
    

Intervention name(s): vNOTES hysterectomy; LSC hysterectomy
Intervention type(s): Procedure; Procedure
Intervention description(s): Surgical removal of the uterus by Natural Orifice Transluminal Endoscopic Surgery using a colpotomy; Surgical removal of the uterus by transabdominal laparoscopy
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: NOTES; Laparoscopic surgery