Improvement of Symptoms After Removal of the Essure® Contraceptive Implant

Implant Complication Clinical Trial

— ABLES  

Official title:

Prospective Multicenter Study of the Improvement of Symptoms After Removal of the Essure® Contraceptive Implant

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06355713
• Other study ID #: 69HCL23_0899
• Secondary ID: 2023-A02010-45
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2024
• Est. completion date: June 1, 2036

Study information

• Verified date: April 2024
• Source: Hospices Civils de Lyon
• Contact: Gautier Chene, PU,PH
• Phone: 0472355870
• Email: gautier.chene[@]chu-lyon.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 Marketed in 2002, ESSURE® contraceptive implants were withdrawn from the French market in 2017 (and worldwide in 2017 and 2018) following the observation in certain patients of polymorphic and non-specific gynecological and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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 444
• Est. completion date: June 1, 2036
• Est. primary completion date: August 1, 2031
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 35 Years to 75 Years

Eligibility

• 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

Related Conditions & MeSH terms

• Contraceptive Device; Complications
• Implant Complication

Intervention

Device:
• Magnetic resonance imaging- Positron Emission Tomography (MRI-PET) examination
An MRI-PET examination will be carried out pre-operatively and at 6 months for the first 20 patients with Essure® and pre-operatively for the first 10 control patients presenting the selection criteria. The duration of each acquisition will be approximately 2 hours. Upon arrival, participants will be greeted by electroradiography technicians. A venous catheter will be placed in a vein in the right or left arm. Participants will be installed in the hybrid MRI-PET imager. The injection of [11C]PK11195 will take place in the MRI-PET acquisition room. Recording of functional neuroimaging data will begin immediately after intravenous injection of [11C]PK11195 and will last for 70 minutes in a resting state. At the end of the examination, the venous catheter will be removed and the visit will be over.

Biological:
• blood sample
Patients with Essure : Blood sample pre-operatively (20 mL) and at 2 months (10 mL) and 12 months (5 mL). Control patients : Blood sample pre-operatively (20 mL)
• urine collection
Patients with Essure : urine collection pre-operatively (10 mL) and at 2 months (10 mL) and 12 months (10 mL). Control patients : urine collection pre-operatively (10 mL)
• Collection of a lock of hair
Patients with Essure : Collection of a lock of hair pre-operatively and at 12 months Control patients : Collection of a lock of hair pre-operatively

Other:
• questionnaire
Questionnaires pre-operatively (except PGI-I) and at 2, 6, 12 months then twice a year up to 5 years for patients with Essure, and pre-operatively (except PGI-I) and at 2 months for control patients : PGI-I: symptom improvement score SF-12: quality of life with physical and mental dimension. FIQ: quality of life of women with fibromyalgia symptoms HADS: anxiety and depressive dimension MFI-20: fatigue according to 5 dimensions ) VAS : pain assessment QDSA: assessment of sensory and emotional impact of pain FSFI : quality of sexual life Higham score

Locations

Country	Name	City	State
France	CHU de Angers	Angers
France	Hôpital Femme Mère Enfant (Hospices Civils de Lyon)	Bron
France	Hôpital Bicêtre	Le Kremlin-Bicêtre
France	Hôpital Jeanne de Flandres	Lille
France	Hôpital de La Conception	Marseille
France	Institut Mère Enfant Alix de Champagne, CHU Reims	Reims
France	CHU de Rouen	Rouen
France	Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg	Strasbourg
France	Hôpital Paule de Viguier, CHU de Toulouse	Toulouse
France	Hôpital André Mignot, Centre Hospitalier de Versailles	Versailles

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients with improvement in symptoms Percentage of patients with improvement in symptoms	Percentage of patients with a score of 1, 2 or 3 (corresponding to improvement in symptoms) on the Patient Global Impression of Improvement (PGI-I) scale.; The PGI-I is a transition scale that is a single question asking the patient to rate their symptoms now, as compared with how it was prior to before beginning treatment on a scale from 1 = Very much better to 7 = Very much worse.	At 2 months after surgical intervention (removal of the Essure® contraceptive implant)
Secondary	Percentage of patients with improvement in symptoms	Percentage of patients with a score of 1, 2 or 3 (corresponding to improvement in symptoms) on the PGI-I scale.; The PGI-I is a transition scale that is a single question asking the patient to rate their symptoms now, as compared with how it was prior to before beginning treatment on a scale from 1 = Very much better to 7 = Very much worse.	up 5 years
Secondary	Short Form 12 (SF-12) score	quality of life with assessment of the physical dimension (from 9.94738 to 70.02246) and the mental dimension (from 5.89058 to 71.96825). For each, the average in the general population is 50.	up 5 years
Secondary	Fibromyalgia Impact Questionnaire (FIQ) score	quality of life of women with fibromyalgia symptoms (from 0 : no symptoms to 100 : important symptoms)	up 5 years
Secondary	Hospital Anxiety and Depression scale (HADS) score	anxiety dimension and depressive dimension (for each dimension, from 0 : no symptom to 21 : certain symptomatology)	up 5 years
Secondary	Multidimensional Fatigue Inventory (MFI)-20 score	Fatigue assessment according to 5 dimensions (General Fatigue, Physical and Mental Fatigue, Reduction in Motivation and Activities) (score from 20 : no fatigue to 100 : important fatigue)	up 5 years
Secondary	Visual analog scale (VAS) score	pain assessment (from 0 : no pain to 100 : unbearable pain)	up 5 years
Secondary	Questionnaire Douleur St-Antoine (QDSA) score	Assessment of sensory impact of pain (from 0: no pain to 36: important impact) and emotional impact of pain (from 0: no pain to 28 : important impact). The global score ranges from 0 to 64.	up 5 years
Secondary	Female Sexual Function Index (FSFI) score	quality of sexual life (from 2 to 36). A low score indicates poorer sexual function.	up 5 years
Secondary	Higham questionnaires	The Higham score is used to quantify blood loss during menstruation. A score = 100 indicates a loss of 80 ml or more, which defines menorrhagia. A score = 150 may indicate an indication for surgery for menometrorrhagia.	up 5 years
Secondary	visual analog scale (VAS) score	Assessment by the surgeon of the difficulty of performing the ablation on a visual analog scale : from 0 (very easy) to 100 mm (very difficult)	During surgical intervention
Secondary	Duration of the procedure	Duration of the procedure (calculated between incision and closure) in number of minutes	During surgical intervention
Secondary	Complications	Number and types of per- and post-operative complications	Up to 2 months after the operation
Secondary	characterization of the mechanical behavior of the implant	characterization of the mechanical behavior of the Essure® device implant will be assessed during tensile breakage and thermal breakage for its two parts (internal part and external part)	During surgical intervention
Secondary	determination of the associated mechanical stress levels determination of the associated mechanical stress levels	determination of the associated mechanical stress levels of the Essure® device implant will be assessed during tensile breakage and thermal breakage for its two parts (internal part and external part)	During surgical intervention
Secondary	quantification of the factors influencing these levels of mechanical stress	quantification of the factors influencing these levels of mechanical stress of the Essure® device implant will be assessed during tensile breakage and thermal breakage for its two parts (internal part and external part)	During surgical intervention
Secondary	thermal resistance	The thermal resistance of the Essure® device implant during coagulations/electrical sections will be assessed.	During surgical intervention
Secondary	risk of degradation	The risk of degradation depending on the temperature f the Essure® device implant used during coagulations/electrical sections will be assessed.	During surgical intervention
Secondary	Concentrations of titanium constituting the Essure® implant	Concentrations of titanium constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Secondary	Concentrations of nickel constituting the Essure® implant	Concentrations of nickel constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Secondary	Concentrations of chromium constituting the Essure® implant	Concentrations of chromium constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Secondary	Concentrations of tin constituting the Essure® implant	Concentrations of tin constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Secondary	Concentrations of platinum constituting the Essure® implant	Concentrations of platinum constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Secondary	Concentrations of iridium constituting the Essure® implant	Concentrations of iridium constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Secondary	Concentrations of molybdenum constituting the Essure® implant	Concentrations of molybdenum constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Secondary	Concentrations of manganese constituting the Essure® implant	Concentrations of manganese constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Secondary	Concentrations of tungsten constituting the Essure® implant	Concentrations of tungsten constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Secondary	Concentrations of silver constituting the Essure® implant	Concentrations of silver constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Secondary	Concentrations of iron constituting the Essure® implant	Concentrations of iron constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Secondary	concentration of pro-inflammatory cytokines	concentration of pro-inflammatory cytokines in the blood will be assessed	Up 2 months after surgical intervention
Secondary	expression profile of miRNAs	Expression profile of miRNAs in the peritoneal fluid will be assessed.	Up 2 months after surgical intervention
Secondary	activated T lymphocyte profile	activated T lymphocyte profile in blood will be assessed.	Up 2 months after surgical intervention
Secondary	analysis of inflammatory pathway mRNAs	analysis of inflammatory pathway mRNAs (nanostring® technology) in a pathology sample from the surgical specimen will be assessed.	Up 2 months after surgical intervention
Secondary	Percentage of detection of Human Leukocyte Antigen	Percentage of detection of Human Leukocyte Antigen (HLA)-DR53 (DRB4*01) associated with nickel allergies in blood will be assessed.	Up 2 months after surgical intervention
Secondary	Functional brain functions	MRI-PET (Magnetic resonance imaging- Positron Emission Tomography) examination : Mapping of brain inflammation: binding potential mapping of [11C]PK11195 characteristic of activated microglia; Brain anatomical imaging: clinical type anatomical MRI examination to assess the presence of cerebral anatomical abnormality; Brain mapping of functional connectivity at rest using Functional magnetic resonance imaging (fMRI); Brain mapping of structural connectivity by diffusion MRI; Perfusion imaging : perfusion MRI examination without contrast product to assess the presence of cerebral perfusion abnormality; Magnetic susceptibility imaging: to detect possible hemorrhages	up 6 months after Surgical intervention