Prospective Multicenter Study of the Improvement of Symptoms After Removal of the Essure® Contraceptive Implant
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 444
- 试验地点
- 20
- 主要终点
- Percentage of patients with improvement in symptoms Percentage of patients with improvement in symptoms
研究概览
简要总结
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 Marketed in 2002, ESSURE® contraceptive implants were withdrawn from the French market in 2017 (and worldwide in 2017 and 2018) following the observation in certain patients of polymorphic and non-specific gynecological and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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Essure Group
Patients requiring removal of the Essure® contraceptive implant
干预措施: blood sample (Biological)
Essure Group
Patients requiring removal of the Essure® contraceptive implant
干预措施: urine collection (Biological)
Essure Group
Patients requiring removal of the Essure® contraceptive implant
干预措施: questionnaire (Other)
Control Group
Control patients who should benefit from a salpingectomy with or without hysterectomy for a benign indication
干预措施: Magnetic resonance imaging- Positron Emission Tomography (MRI-PET) examination (Device)
Control Group
Control patients who should benefit from a salpingectomy with or without hysterectomy for a benign indication
干预措施: blood sample (Biological)
Control Group
Control patients who should benefit from a salpingectomy with or without hysterectomy for a benign indication
干预措施: urine collection (Biological)
Essure Group
Patients requiring removal of the Essure® contraceptive implant
干预措施: Magnetic resonance imaging- Positron Emission Tomography (MRI-PET) examination (Device)
Control Group
Control patients who should benefit from a salpingectomy with or without hysterectomy for a benign indication
干预措施: Collection of a lock of hair (Biological)
Essure Group
Patients requiring removal of the Essure® contraceptive implant
干预措施: Collection of a lock of hair (Biological)
Control Group
Control patients who should benefit from a salpingectomy with or without hysterectomy for a benign indication
干预措施: questionnaire (Other)
结局指标
主要结局
Percentage of patients with improvement in symptoms Percentage of patients with improvement in symptoms
时间窗: At 2 months after surgical intervention (removal of the Essure® contraceptive implant)
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.
次要结局
- Fibromyalgia Impact Questionnaire (FIQ) score(up 5 years)
- Multidimensional Fatigue Inventory (MFI)-20 score(up 5 years)
- Visual analog scale (VAS) score(up 5 years)
- visual analog scale (VAS) score(During surgical intervention)
- Questionnaire Douleur St-Antoine (QDSA) score(up 5 years)
- Female Sexual Function Index (FSFI) score(up 5 years)
- characterization of the mechanical behavior of the implant(During surgical intervention)
- determination of the associated mechanical stress levels determination of the associated mechanical stress levels(During surgical intervention)
- Percentage of patients with improvement in symptoms(up 5 years)
- Short Form 12 (SF-12) score(up 5 years)
- Hospital Anxiety and Depression scale (HADS) score(up 5 years)
- Higham questionnaires(up 5 years)
- Duration of the procedure(During surgical intervention)
- Complications(Up to 2 months after the operation)
- quantification of the factors influencing these levels of mechanical stress(During surgical intervention)
- Concentrations of titanium constituting the Essure® implant(up 12 months after surgical intervention)
- Concentrations of nickel constituting the Essure® implant(up 12 months after surgical intervention)
- Concentrations of chromium constituting the Essure® implant(up 12 months after surgical intervention)
- Concentrations of tin constituting the Essure® implant(up 12 months after surgical intervention)
- thermal resistance(During surgical intervention)
- risk of degradation(During surgical intervention)
- Concentrations of molybdenum constituting the Essure® implant(up 12 months after surgical intervention)
- Concentrations of manganese constituting the Essure® implant(up 12 months after surgical intervention)
- concentration of pro-inflammatory cytokines(Up 2 months after surgical intervention)
- analysis of inflammatory pathway mRNAs(Up 2 months after surgical intervention)
- Concentrations of platinum constituting the Essure® implant(up 12 months after surgical intervention)
- Concentrations of iridium constituting the Essure® implant(up 12 months after surgical intervention)
- Concentrations of silver constituting the Essure® implant(up 12 months after surgical intervention)
- Concentrations of iron constituting the Essure® implant(up 12 months after surgical intervention)
- Functional brain functions(up 6 months after Surgical intervention)
- Concentrations of tungsten constituting the Essure® implant(up 12 months after surgical intervention)
- expression profile of miRNAs(Up 2 months after surgical intervention)
- activated T lymphocyte profile(Up 2 months after surgical intervention)
- Percentage of detection of Human Leukocyte Antigen(Up 2 months after surgical intervention)