Evaluation of a Subcutaneous Progestogen Implants in the Medical Management of Painful Endometriosis (END-IMPACT)

Endometriosis is a chronic relapsing disease characterized by the presence and proliferation of endometrial glands and stroma outside the uterus. This is a serious disease, widespread, difficult to live with for the patients, but also difficult to treat for practitioners who take care of these patients. It affects 1.6% of the general population, but its incidence is 10 times higher (up 40%) in patients with infertility. It occurs mainly by complex chronic pelvic pain and a negative influence on fertility.

It is a disease whose complexity can be explained to four levels. Firstly, through its extremely polymorphic character with intraperitoneal superficial forms, ovarian forms and deep sub-peritoneal forms.

Secondly by the plurality of the main symptoms which are individually non-specific and the frequency and / or intensity is not correlated with the severity of the disease. This non-specificity of symptoms partially explains the long lead misdiagnosis, which vary by 5 to 11 years.

Thirdly, by its prevalence which seems very high and largely underestimated. If its precise estimate in the general population is so complicated, it seems very high in many studies of patients supported surgically for gynecological reasons. These very large prevalence figures are observed when some consultations support the hypothesis of a widespread and probably insufficiently evaluated disease.

Lately by its management, insufficiently amended, for which there is currently only a few scientifically supported recommendations.

Chronic pain caused by the disease associated with altered sexuality to a loss of fertility significantly impacts the quality of life of patients.

Study Overview

• Status: Terminated
• Conditions: Endometriosis
• Intervention / Treatment: Device: Nexplanon®; Drug: Minidril®/Leeloo®

Detailed Description

Investigators propose a randomized trial comparing two medical alternatives: a continuous monophasic type of estrogen-progestin oral treatment of second generation versus the establishment of an etonogestrel contraceptive implant type.

Are excluded from this study certain absolute surgical indications. Patients, by consenting to participate in the study, choose a medical care, which means not to be operated immediately. They are clearly informed about the various possible treatment alternatives. The benefits and risks of surgery and medical treatment they are explicitly presented. At any time during the study, patients who wish may discuss again a surgical treatment with their physician and stop the study drug if the decision of an intervention is taken.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Réunion
  • Saint Denis
    • Saint-Denis, Saint Denis, Réunion, 97400
      • CHU de la Réunion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Between 18 and 45 years old
• with a painful symptomatic endometriosis
• with symptoms evolve for more than 6 months
• diagnosis based on clinical and radiological criteria : pain in the examination and/or palpation of endometriosis lesion(s) and lesion(s) objectified by MRI performed and interpreted by a radiologist referent dating less than three months at the time of inclusion
• no history presenting therapeutic surgery for endometriosis
• Accepting medical management
• without hormonal treatment (oestroprogestative, progestative or Luteinizing Hormone-Releasing Hormone (LHRH) analog) since at least 15 days
• No family history of deep venous thromboembolic disorders
• No abnormalities of hemostasis known
• Not pregnant at inclusion visit

Exclusion Criteria:

• Patient with a strict indication for surgery (ureteral disease with renal impact, digestive disease with occlusion, infertility with desire for immediate pregnancy, ovarian cyst ≥ 4cm)
• reproductive upper tract infections
• with one or more varicose veins
• with one or more breast abnormalities (ACR 3 or more)
• with contraindication for one of two treatments
• with contraindication for RMI
• taking drug treatment that could alter the concentration of the study treatments

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Implant; Subcutaneous insertion of an progestative implant containing 68mg of etonogestrel	Device: Nexplanon®; Subcutaneous implant (Nexplanon®) containing etonogestrel 68 mg
Active Comparator: Oral treatment; Continuous oral administration of second generation monophasic oestro-progestative (ethinyl-oestradiol)	Drug: Minidril®/Leeloo®; continuous per os administration of oestroprogestative treatment. 1 pill a day First line: Minidril® (Levonogestrel 0.15 mg / Ethinylestradiol 0.03 mg) Second line: Leeloo® (Levonogestrel 0.1 mg / Ethinylestradiol 0.02 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global satisfaction	Global satisfaction evaluated by the SATMED-Q® satisfaction score at 6th month.	6th month of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain evaluation	Pain evaluation from analogical visual scale	6th and 12th month
Daily life impact	Evaluation of daily life impact of endometriosis with Endometriosis Health Profile - 30 (EHP-30)	6th and 12th month
Sex life impact	Evaluation of sexual life impact of endometriosis with Female Sexual Function Index (FSFI)	6th and 12th month
Evaluation of dysmenorrhea, dyspareunia and pelvic pain	Evaluation of frequency and intensity of dysmenorrhea, dyspareunia and pelvic pain with Biberoglu scale	6th and 12th month
Quality of life score	Evaluation of quality of life impact of endometriosis with SF36 scale	6th and 12th month
Number of lesions	The number, size, localisation and activity of the lesions is evaluated by Resonance Magnetic Image	Day 1 and 12th month
size of lesions	Size of the lesions (mm) is evaluated by Resonance Magnetic Image	Day 1 and 12th month
Localisation of lesions	Localisations of the lesions is evaluated by Resonance Magnetic Image	Day 1 and 12th month
Incidence of treatment-emergent adverse events (safety and tolerability)	percentage of clinical and biological adverse effects	3rd, 6th, 9th and 12th month

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de la Réunion
• Investigators: Principal Investigator: Anca BIRSAN, MD

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2018
• Primary Completion (Actual): October 10, 2019
• Study Completion (Actual): October 10, 2019

Study Registration Dates

• First Submitted: October 22, 2015
• First Submitted That Met QC Criteria: January 27, 2016
• First Posted (Estimate): February 1, 2016

Study Record Updates

• Last Update Posted (Actual): March 4, 2020
• Last Update Submitted That Met QC Criteria: March 3, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endometriosis; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Etonogestrel
• Other Study ID Numbers: 2015/CHU/03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No