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

NCT ID: NCT04804332

Last Updated: 2024-05-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 244 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-12
• Study Completion Date: 2027-12-30

Brief Summary

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.

Detailed Description

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.

Conditions

Retained Products of Conception

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

EXPECTANT MANAGEMENT

No treatment will be offered.

Group Type: EXPERIMENTAL

Expectant management

Intervention Type: OTHER

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.

OPERATIVE HYSTEROSCOPY

Operative hysteroscopy using hysteroscopic morcellation (TruClearTM Hysteroscopic Tissue Removal System (Medtronic, Minneapolis, MN, USA)) is performed.

Group Type: EXPERIMENTAL

Operative hysteroscopy

Intervention Type: PROCEDURE

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 gynecologist using hysteroscopic morcellation (TruClearTM Hysteroscopic Tissue Removal System (Medtronic, Minneapolis, MN, USA)) and according to the local protocol.

Interventions

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 gynecologist using hysteroscopic morcellation (TruClearTM Hysteroscopic Tissue Removal System (Medtronic, Minneapolis, MN, USA)) and according to the local protocol.

Intervention Type: PROCEDURE

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 39 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Medtronic

INDUSTRY

Sponsor Role: collaborator

University Hospital, Ghent

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tjalina Hamerlynck, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Ghent

Locations

Ghent University Hospital

Ghent, , Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Eline Meireson

Role: CONTACT

eline.meireson@uzgent.be

+3293327817

Facility Contacts

Eline Meireson, Msc

Role: primary

eline.meireson@uzgent.be

+3293327817

Other Identifiers

BC-08856

Identifier Type: -

Identifier Source: org_study_id