MEdical Versus SUrgical Treatments of Rectal Endometriosis (MESURE)

Randomized Trial Comparing Functional Digestive Outcomes Related to Two Types of Management of Rectal Endometriosis: Continuous Hormonal Treatment and Curative Surgery

The purpose of this study is to determine whether, in women with deep endometriosis involving the rectum and not intending to get pregnant, continuous hormonal treatment would be followed by better digestive functional outcomes than curative rectal surgery. Are included women from 35 to 50 years presenting with deep endometriosis infiltrating at least the muscular layer of the rectum and not having pregnancy intention.

The main outcome concerns the quality of digestive function 24 after the onset of the treatment, assessed using a composite variable: patient considering that digestive function is normal AND the Knowles-Eccersley-Scott-Symptom Questionnaire (KESS score) <7 AND the Gastrointestinal Quality of Life Index (GIQLI) score >100.

Secondary outcomes are: presence of severe constipation, increased frequency of daily bowel movements, anal incontinence, postoperative dysuria, Biberoglou & Behrman score, quality of life SF36 score, KESS score, GIQLI, Wexner score of anal continence, Bristol stools score, the rate of postoperative complications, medical treatment adverse outcomes, the rate of additional endoscopic and surgical procedures.

The randomization is central, once the physician asses the diagnosis, explain the study's principle and rece In the arm A, the patients received triptoreline and add back therapy by estradiol during 6 months, followed by daily intake of cyproterone acetate and add back therapy during 18 months.

In the arm B, patients are managed by rectal surgery (depending on the surgeon choice: rectal shaving, rectal disc excision or colorectal resection) followed by the prevention of recurrences by daily intake of cyproterone acetate and add back therapy during 18 months.

The number of subjects required is 78 (39 on each arm). Inclusions period is estimated at 24 months. The length of the follow up is 24 months. The patients have 8 visits in the arm A, and 7 visits in the arm B.

Eleven French tertiary referral centres will enrol patients in the trial.

Study Overview

• Status: Unknown
• Conditions: Endometriosis
• Intervention / Treatment: Drug: Triptoreline 11.25 i.v.; Estradiol 0.5% percutaneous gel;; Drug: Cyproterone acetate 50 mg; estradiol 0.5% percutaneous; Procedure: rectal shaving; rectal disc excision; colorectal resection; Drug: Estradiol 0.5% percutaneous gel; Cyproterone acetate 50 mg oral

• Study Type: Interventional
• Enrollment (Anticipated): 78
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Horace Roman, MD PhD; Phone Number: +33232888745; Email: horace.roman@gmail.com

Study Locations

• France
  • Amiens, France, 80054
    • Not yet recruiting
    • CHU d'Amiens
    • Contact: Sophie Sanguin, MD; Phone Number: +333 22 53 36 23; Email: sanguinsophie@aol.com
    • Principal Investigator: Sophie Sanguin
  • Clermont-ferrand, France, 63000
    • Not yet recruiting
    • Service de Gynécologie, Obstétrique et Médecine de la Reproduction CHU de CLERMONT-FERRAND Hôpital ESTAING 1 place Lucie Aubrac
    • Sub-Investigator: Nicolas Bourdel, MD
    • Contact: Michel Canis, MD PhD; Phone Number: +334 73 75 01 38; Email: mcanis@chu-clermontferrand.fr
  • Dijon, France, 21079
    • Not yet recruiting
    • CHU de Dijon
    • Contact: Paul Sagot, MD PhD; Phone Number: +333 80 29 38 52; Email: paul.sagot@chu-dijon.fr
    • Principal Investigator: Paul Sagot
  • Kremlin Bicetre, France, 94270
    • Not yet recruiting
    • Service de Gynécologie-Obstétrique AP-HP Hôpital du KREMLIN BICETRE
    • Contact: Herve Fernandez, MD PhD; Phone Number: +331 45 21 77 01; Email: herve.fernandez@bct.aphp.fr
    • Principal Investigator: Herve Fernandez, MDPhD
  • Le Chesnay, France, 78157
    • Not yet recruiting
    • Hôpital du CHESNAY
    • Contact: Pierre Panel, MD; Phone Number: +331 39 63 97 33; Email: PPANEL@ch-versailles.fr
    • Principal Investigator: Pierre Panel
  • Lille, France, 59037
    • Not yet recruiting
    • Clinique Gynécologique CHRU de LILLE
    • Contact: Chrystele Rubod, MCUPH; Phone Number: +333 20 44 67 57; Email: chrystele.rubod@chu-lille.fr
    • Principal Investigator: Chrystele Rubod
  • Nimes, France, 39900
    • Not yet recruiting
    • Service de Gynécologie-Obstétrique CHU de NIMES
    • Principal Investigator: Renaud DE TAYRAC, MD PhD
    • Contact: RenaudTayrac de Tayrac, MD PhD; Phone Number: +336 03 26 32 32; Email: renaud.detayrac@chu-nimes.fr
  • Paris, France, 75020
    • Not yet recruiting
    • Hôpital de Tenon
    • Contact: Emile Darai, MD PhD; Email: emile.darai@tnn.aphp.fr
    • Sub-Investigator: Marcos Bellester
  • Poissy, France, 78103
    • Not yet recruiting
    • Chi Poissy-St Germain En Laye Poissy
    • Contact: Arnaud Fauconnier, MD PhD; Phone Number: +331 39 27 52 51; Email: afauconnier@chi-poissy-st-germain.fr
    • Principal Investigator: Arnaud Fauconnier
  • Rouen, France, 76031
    • Recruiting
    • Clinique Gynécologique et Obstétricale
    • Contact: Horace Roman, MD PhD; Phone Number: +33232888745; Email: horace.roman@gmail.com
    • Principal Investigator: Horace Roman, MD PhD
  • Strasbourg, France, 67000
    • Not yet recruiting
    • CHU de STRASBOURG STRASBOURG
    • Contact: Arnaud Wattiez, MD PhD; Phone Number: +333 88 12 74 55; Email: arnaud.wattiez@ircad.fr
    • Principal Investigator: Arnaud Wattiez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age 35-50
• No menopause
• Digestive complaints: defecation pain, dyskesia, diarrhea, constipation, rectorrhage
• Imaging assessment revealing deep endometriosis involving at least the muscular rectal layer
• No intention to get pregnant during the following 24 months
• Negative urinary pregnancy test
• Affiliated to the French Social Security System

Exclusion Criteria:

• Pregnant women or during the breastfeeding
• Pregnancy intention or lack of efficient contraception
• Unexpected rectal endometriosis intraoperatively revealed
• Refus of one of treatments planned in the two arms
• Severe disease requiring surgical treatment in emergency (bowel occlusion, ureteral stenosis or hydronephrosis), severe dyspareunia
• Contraindications to hormonal treatment or surgery
• Major thromboembolic factors
• Antecedents of inflammatory bowel diseases, cancer or colorectal resection
• Vaginal hemorrhage with undetermined etiology

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Medical treatment; The patients received triptoreline and add back therapy by estradiol during 6 months, followed by daily intake of cyproterone acetate and add back therapy during 18 months.	Drug: Triptoreline 11.25 i.v.; Estradiol 0.5% percutaneous gel; Triptoreline 11.25 administered for 3 months, two consecutive cures Estradiol administered daily for 6 months; Drug: Cyproterone acetate 50 mg; estradiol 0.5% percutaneous; Daily intake for 18 months
Active Comparator: Surgical; The patients are managed by rectal surgery (depending on the surgeon choice: rectal shaving, rectal disc excision or colorectal resection) followed by the prevention of recurrences by daily intake of cyproterone acetate and add back therapy during 18 months.	Procedure: rectal shaving; rectal disc excision; colorectal resection; Drug: Estradiol 0.5% percutaneous gel; Cyproterone acetate 50 mg oral; Daily intake during 24 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative digestive function	Composite variable: patient considering that digestive function is normal AND the Knowles-Eccersley-Scott-Symptom Questionnaire (KESS score) <7 AND the Gastrointestinal Quality of Life Index (GIQLI) score >100.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Unfavorable digestive functional outcome	Presence of severe constipation (<1 stool/5D), increased frequency of daily bowel movements (>=3 stools/D), anal incontinence, postoperative dysuria	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of digestive function	The Knowles-Eccersley-Scott-Symptom Questionnaire (KESS score), the Gastrointestinal Quality of Life Index (GIQLI), Wexner score of anal continence, Bristol stools score.	24 months

Collaborators and Investigators

• Sponsor: University Hospital, Rouen

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Anticipated): March 1, 2018
• Study Completion (Anticipated): November 1, 2019

Study Registration Dates

• First Submitted: October 25, 2013
• First Submitted That Met QC Criteria: October 31, 2013
• First Posted (Estimate): November 1, 2013

Study Record Updates

• Last Update Posted (Actual): June 14, 2017
• Last Update Submitted That Met QC Criteria: June 13, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: deep endometriosis;; bowel endometriosis; rectal endometriosis;; rectal shaving;; colorectal resection
• Additional Relevant MeSH Terms: Endometriosis; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Estrogens; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Androgen Antagonists; Luteolytic Agents; Contraceptive Agents, Male; Estradiol; Triptorelin Pamoate; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate; Cyproterone Acetate; Cyproterone
• Other Study ID Numbers: 2013/001/HP