Removal of Intrauterine Retained Products of Conception (RPOC) After Miscarriage Guided by Hysteroscopy Trial. A Randomized Controlled Trial.

Обзор

Rationale: Elective immediate dilation and curettage (D\&C) for miscarriage is associated with the occurrence of intrauterine adhesions (IUA). IUAs may be associated with subsequent subfertility and premature birth. Recent studies have shown that in women with miscarriage, medical treatment (misoprostol/mifepristone) is an effective alternative for curettage. A problem with medication and expectant management is that after initial treatment, sonographic findings during follow-up frequently show incomplete evacuation of uterine retained products of conception (RPOC), which often lead to additional interventions or expectant time-consuming management limiting the benefits of medical treatment. Objective: To assess, in women with a wish for immediate future pregnancy and RPOC after non-surgical management of a miscarriage, as diagnosed with sonography, the effects of operative hysteroscopy versus expectant management. Study design: Multicenter randomized clinical trial. Study population: Patients after non-surgical management of a miscarriage with sonographic evidence of RPOC at the follow-up visit 6 weeks after initial treatment and wish for immediate (within 6 months) future pregnancy. Intervention: operative hysteroscopy versus expectant management. Main study parameters/endpoints: The primary outcome is time to next pregnancy, as substantiated by a positive urinary or serum hCG test. Secondary outcomes are Quality of Life (QOL) scores assessed with the SF-36, HADS and EQ-5D-5L, the need for additional and/or unscheduled treatments and/or visits and complications. Furthermore, data on the course of pregnancy - including miscarriage, ectopic pregnancy and live birth - are documented in those women who have an ongoing pregnancy after randomization during the study follow up period. In addition, iMTA PCQ questionnaires and health-costs are measured in all patients to perform a cost-effectiveness analysis. A total of 244 (122 per arm) women will be sufficient to answer the questions on the primary endpoint. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Women participating in the study will be asked to fill out questionnaires at baseline, 8 weeks and 6 months after randomization. We don not expect specific risks as a result of either the intervention or expectant management.

Подробное описание

Design : RCT

* Multicenter * Randomized controlled * Parallel group design * Superiority trial * Non-blinded

Primary Objective

To compare the effectiveness in terms of time to next pregnancy between operative hysteroscopy and expectant management in patients with sonographic evidence of RPOC after primary non-surgical management of miscarriage.

Secondary Objectives

1. Effectiveness objectives

To compare the effectiveness between operative hysteroscopy and expectant management with respect to: * Generic quality of life (QOL) (as measured by SF-36, HADS (Hospital Anxiety and Depression Scale)) and EQ-5D-5L 6 months after randomization * Course of pregnancy in those women who have an ongoing pregnancy after randomization during the study follow-up period (including miscarriage, ectopic pregnancy and live birth) 2. Safety objectives

To compare the safety between operative hysteroscopy and expectant management with respect to: * Necessity for additional treatment * Out-of-protocol/unscheduled visits to the outpatient clinic or general practitioner * Complications 3. Cost-effectiveness objectives To compare the health related costs between operative hysteroscopy and expectant management.

Вмешательства

• Процедура Operative hysteroscopy
  Operative hysteroscopy is performed without or under local, regional or general anesthesia according to the local protocol preferably within 2 to 3 weeks after randomization. In case of highly vascularized RPOC, a repeat sonogram is performed 2 to 4 weeks after randomization to check for persistence of vascularity and to optimize operative timing. Operative hysteroscopy is then performed within 2 to 3 weeks after the repeat sonogram. Removal of the RPOC is performed by an experienced gynecologis
• Другое Expectant management
  No treatment will be offered. Patients will be given telephone numbers to contact a doctor. In case of severe complaints, defined as heavy uterine bleeding and/or severe abdominal pain, not responding to conservative treatment, an emergency curettage or operative hysteroscopy may be performed.

Первичные конечные точки

• Time to next pregnancy [Срок оценки: up to 3 years after the start of the trial]

Вторичные конечные точки (11)

• Quality Of Life (QOL) [Срок оценки: at baseline, 8 weeks after randomization and 6 months after randomization]
• Quality Of Life (QOL) [Срок оценки: at baseline, 8 weeks after randomization and 6 months after randomization]
• Quality Of Life (QOL) [Срок оценки: at baseline, 8 weeks after randomization and 6 months after randomization]
• Course of pregnancy [Срок оценки: up to 3 years after the start of the trial]
• Necessity for additional treatment [Срок оценки: until 6 months after randomisation]
• Out-of-protocol/unscheduled visits [Срок оценки: until 6 months after randomisation]
• Complications [Срок оценки: until 6 months after randomisation]
• Complications [Срок оценки: until 6 months after randomisation]
• Complications [Срок оценки: until 6 months after randomisation]
• Complications [Срок оценки: until 6 months after randomisation]
• Health related costs [Срок оценки: until 6 months after randomisation]

Критерии участия

Критерии включения

• Patients after first trimester miscarriage treated non-surgically with sonographic evidence for the presence of RPOC at follow-up visit after 6 weeks (± 1 week) who have an immediate future pregnancy wish and are willing to give informed consent.

Критерии исключения

• Women aged below 18 years
• Women aged over 39 years
• Women not wanting to achieve pregnancy within the first 6 months after non-surgical treatment for miscarriage
• Women with a history of repeated miscarriage defined as 3 or more consecutive pregnancy losses before 20 weeks of pregnancy duration
• Women with untreated and/or untreatable subfertility
• Women presenting with severe uterine bleeding, defined as uterine bleeding that needs acute intervention on medical grounds
• Women presenting with severe abdominal pain, defined as abdominal pain that needs acute intervention on medical grounds
• Women with fever (> 38.5° Celsius) or sepsis requiring antibiotic treatment. For the definition of 'sepsis' we refer to the Third International Consensus definitions for Sepsis and Septic Shock (Singer 2016)
• Women with a contraindication for (office) operative hysteroscopy
• Women with a failed non-surgical management for miscarriage, as substantiated by the sonographic finding of an intact gestational sac still in situ
• Women with a congenital uterine anomaly
• Known cervical stenosis making safe uterine access impossible
• Visual or pathological (e.g. on biopsy) evidence of malignancy

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Бельгия · 1 центр

• Ghent University Hospital — Ghent

Идентификаторы

NCT: NCT04804332 · BC-08856

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗