Clinical trial NCT06355713: Improvement of Symptoms After Removal of the Essure® Contraceptive Implant
Official title: Prospective Multicenter Study of the Improvement of Symptoms After Removal of the Essure® Contraceptive Implant
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Implant Complication
Contraceptive Device; Complications
Keywords: Essure implant
Contraceptive implant
Symptoms
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2024-04-09
Enrollment: 444
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: ESSURE® is an implantable medical device for definitive and irreversible sterilization indicated for adult women of childbearing age. These implants are inserted into the fallopian tubes by hysteroscopy. Marketed in 2002, ESSURE® contraceptive implants were withdrawn from the French market in 2017 (and worldwide in 2017 and 2018) following the observation in certain patients of polymorphic and non-specific gynecological and extra-gynecological symptoms. Studies with small numbers and short-term follow-up have shown a significant improvement in these symptoms after implant explantation. This constitutes a real public health problem since according to the report of the EPI-PHARE Scientific Interest Group, 198,000 French women have these implants and only 30,000 of them, or 15%, have been explanted, knowing that explantation of ESSURE® implants is recommended only in symptomatic patients. A large number of these patients, presenting symptoms, have not yet been treated for an explant.

The physiopathological mechanism(s) is (are) not yet determined but several arguments are in favor of a dissemination of metallic elements contained in these implants whose accumulation could lead to inflammatory and/or allergic and/or autoimmune phenomena.

Carrying out a prospective study with long-term longitudinal follow-up appears essential to precisely assess the degree of improvement in the symptoms and quality of life of these patients, determine the most appropriate surgical techniques, and understand the pathophysiological mechanisms that may result in the implementation of specific treatments and relevant markers. From a surgical point of view, there is a real risk of fracture of implants whatever the type of intervention performed: study the biomechanical properties of implants with a view to characterizing their behavior to mechanical rupture but also their thermal resistance in an objective manner seems essential to limit the risk of fracture and help to inform the patient about the surgical technique proposed for explantation. From a biological point of view, the dosage of the metallic elements constituting ESSURE® implants and potentially toxic ones could make it possible to objectify the release of these metallic elements in the body. Analysis of pro-inflammatory cytokines, micro-RNAs (miRNA), quantitative analysis of inflammatory pathway messenger ribonucleic acid (mRNAs) (NanoString technology) and analysis of neuroinflammation by functional imaging should make it possible to explore potential pathophysiological mechanisms. This study responds to a significant request from patient associations.


Eligibility criteria: * Inclusion Criteria \* :

ESSURE Group:

* woman aged 35 to 75
* patient with at least one Essure® implant
* surgical intervention planned because the patient is symptomatic: removal of the Essure® implant(s)
* planned intervention via vaginal route, laparoscopy, robotic surgery, or Transvaginal natural orifice transluminal endoscopic surgery (VNotes)
* patient having given free, informed and signed consent

Selection for MRI-PET examination:

* if the answer is "poor" or "bad" to the first question of the SF-12 pre-operatively
* no hysterectomy
* no analgesic treatment, or treatment stopped 48 hours before the examination
* no psychotropic treatment (anxiolytics, hypnotics (sleeping pills), antidepressants, mood stabilizers, neuroleptics)
* patient having given free, informed and signed consent

Control group:

* woman aged 35 to 75
* planned surgical intervention: salpingectomy with or without hysterectomy for benign indication
* planned intervention via vaginal route, laparoscopy, robotic surgery, or VNotes
* patient having given free, informed and signed consent

Selection for MRI-PET examination:

* age matching (+/- 5 years) with Essure® patients who have had an MRI-PET
* matching on surgical technique with Essure® patients who have had an MRI-PET: salpingectomy with or without hysterectomy
* no analgesic treatment, or treatment stopped 48 hours before the examination
* no psychotropic treatment (anxiolytics, hypnotics (sleeping pills), antidepressants, mood stabilizers, neuroleptics)
* patient having given free, informed and signed consent

  * Exclusion Criteria \* :

ESSURE Group:

* asymptomatic patient
* planned intervention by laparotomy
* patient potentially exposed to other heavy metals: wearer of metallic orthopedic equipment (hip or knee prosthesis, etc.), wearer of coronary stent, or tubal ligation clip
* inability to understand the information given
* persons deprived of liberty by a judicial or administrative decision
* people undergoing psychiatric care
* people admitted to a health or social establishment for purposes other than research
* adults subject to a legal protection measure (guardianship, curatorship)
* people not affiliated to a social security scheme or beneficiaries of a similar scheme
* person participating in another interventional research that may interfere with the research

Selection for MRI-PET examination:

* claustrophobia
* dosimetry of all radiological examinations over the past year not acceptable

Control Group :

* current pregnancy
* patient with cancer
* patient who has already had an Essure® implant removed
* patient potentially exposed to heavy metals: wearer of metallic orthopedic equipment (hip or knee prosthesis, etc.), wearer of coronary stent, or tubal ligation clip
* planned intervention by laparotomy
* inability to understand the information given
* persons deprived of liberty by a judicial or administrative decision
* people undergoing psychiatric care
* people admitted to a health or social establishment for purposes other than research
* adults subject to a legal protection measure (guardianship, curatorship)
* people not affiliated to a social security scheme or beneficiaries of a similar scheme
* person participating in another interventional research that may interfere with the research

Selection for MRI-PET examination:

* claustrophobia
* dosimetry of all radiological examinations over the past year not acceptable

Primary outcomes:
measure: Percentage of patients with improvement in symptoms Percentage of patients with improvement in symptoms
timeFrame: At 2 months after surgical intervention (removal of the Essure® contraceptive implant)
Secondary outcomes:
measure: Percentage of patients with improvement in symptoms
timeFrame: up 5 years
measure: Short Form 12 (SF-12) score
timeFrame: up 5 years
measure: Fibromyalgia Impact Questionnaire (FIQ) score
timeFrame: up 5 years
measure: Hospital Anxiety and Depression scale (HADS) score
timeFrame: up 5 years
measure: Multidimensional Fatigue Inventory (MFI)-20 score
timeFrame: up 5 years
measure: Visual analog scale (VAS) score
timeFrame: up 5 years
measure: Questionnaire Douleur St-Antoine (QDSA) score
timeFrame: up 5 years
measure: Female Sexual Function Index (FSFI) score
timeFrame: up 5 years
measure: Higham questionnaires
timeFrame: up 5 years
measure: visual analog scale (VAS) score
timeFrame: During surgical intervention
measure: Duration of the procedure
timeFrame: During surgical intervention
measure: Complications
timeFrame: Up to 2 months after the operation
measure: characterization of the mechanical behavior of the implant
timeFrame: During surgical intervention
measure: determination of the associated mechanical stress levels determination of the associated mechanical stress levels
timeFrame: During surgical intervention
measure: quantification of the factors influencing these levels of mechanical stress
timeFrame: During surgical intervention
measure: thermal resistance
timeFrame: During surgical intervention
measure: risk of degradation
timeFrame: During surgical intervention
measure: Concentrations of titanium constituting the Essure® implant
timeFrame: up 12 months after surgical intervention
measure: Concentrations of nickel constituting the Essure® implant
timeFrame: up 12 months after surgical intervention
measure: Concentrations of chromium constituting the Essure® implant
timeFrame: up 12 months after surgical intervention
measure: Concentrations of tin constituting the Essure® implant
timeFrame: up 12 months after surgical intervention
measure: Concentrations of platinum constituting the Essure® implant
timeFrame: up 12 months after surgical intervention
measure: Concentrations of iridium constituting the Essure® implant
timeFrame: up 12 months after surgical intervention
measure: Concentrations of molybdenum constituting the Essure® implant
timeFrame: up 12 months after surgical intervention
measure: Concentrations of manganese constituting the Essure® implant
timeFrame: up 12 months after surgical intervention
measure: Concentrations of tungsten constituting the Essure® implant
timeFrame: up 12 months after surgical intervention
measure: Concentrations of silver constituting the Essure® implant
timeFrame: up 12 months after surgical intervention
measure: Concentrations of iron constituting the Essure® implant
timeFrame: up 12 months after surgical intervention
measure: concentration of pro-inflammatory cytokines
timeFrame: Up 2 months after surgical intervention
measure: expression profile of miRNAs
timeFrame: Up 2 months after surgical intervention
measure: activated T lymphocyte profile
timeFrame: Up 2 months after surgical intervention
measure: analysis of inflammatory pathway mRNAs
timeFrame: Up 2 months after surgical intervention
measure: Percentage of detection of Human Leukocyte Antigen
timeFrame: Up 2 months after surgical intervention
measure: Functional brain functions
timeFrame: up 6 months after Surgical intervention
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU de Angers
city: Bron
country: France
facility: Hôpital Femme Mère Enfant (Hospices Civils de Lyon)
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital Bicêtre
city: Lille
country: France
facility: Hôpital Jeanne de Flandres
city: Marseille
country: France
facility: Hôpital de La Conception
city: Reims
country: France
facility: Institut Mère Enfant Alix de Champagne, CHU Reims
city: Rouen
country: France
facility: CHU de Rouen
city: Strasbourg
country: France
facility: Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg
city: Toulouse
country: France
facility: Hôpital Paule de Viguier, CHU de Toulouse
city: Versailles
country: France
facility: Hôpital André Mignot, Centre Hospitalier de Versailles
Study officials:
References: