Removal of Intrauterine Retained Products of Conception (RPOC) After Miscarriage Guided by Hysteroscopy Trial. A Randomized Controlled Trial. (RIGHT)
Primary Purpose
Retained Products of Conception
Status
Recruiting
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
Operative hysteroscopy
Expectant management
Sponsored by
About this trial
This is an interventional treatment trial for Retained Products of Conception focused on measuring Retained Products of Conception, placental remnants, hysteroscopy, expectant management, fertility
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
Sites / Locations
- Ghent University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
EXPECTANT MANAGEMENT
OPERATIVE HYSTEROSCOPY
Arm Description
No treatment will be offered.
Operative hysteroscopy using hysteroscopic morcellation (TruClearTM Hysteroscopic Tissue Removal System (Medtronic, Minneapolis, MN, USA)) is performed.
Outcomes
Primary Outcome Measures
Time to next pregnancy
The primary endpoint is the time until next pregnancy since randomization, with pregnancy defined as a positive urinary or serum hCG test. Patients are asked to contact the study team in case of pregnancy. If a participant has failed to contact the center, pregnancy will be asked at same time as the questionnaires and then once every 6 months as well as at the end of the study by telephone contact or e-mail.
Secondary Outcome Measures
Quality Of Life (QOL)
measured by SF-36
Quality Of Life (QOL)
measured by HADS (Hospital Anxiety and Depression Scale)
Quality Of Life (QOL)
measured by EQ-5D-5L
Course of pregnancy
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):
Time to conception, defined as the time from randomization to the date of conception retrospectively determined based on the crown-rump length measurement (CRL) by a first-trimester ultrasound.
Clinical pregnancy defined as a pregnancy diagnosed by ultrasonographic visualization of 1 or more gestational sacs or definitive clinical signs of pregnancy, including ectopic pregnancy. Multiple gestational sacs are counted as 1 clinical pregnancy.
Live birth, defined as the complete expulsion or extraction from the mother of a product of fertilization, irrespective of the duration of pregnancy, which after such separation breathes or shows any other evidence of life, such as heartbeat, umbilical cord pulsation, or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been
Necessity for additional treatment
Necessity for additional treatment
Out-of-protocol/unscheduled visits
Re-interventions or additional treatment during the first 6 months including type, number and reasons.
Out-of-protocol visits to the outpatient clinic or general practitioner or hospitalizations including type, number, reasons and duration of hospitalization.
Complications
Heavy uterine bleeding defined as uterine bleeding that needs acute intervention (IV iron administration, tranexamic acid or blood transfusion) on medical grounds
Complications
Severe abdominal pain requiring analgesics or medical intervention, excluding postoperative pain in the first 48 hours after uterine surgery
Complications
Fever (>38.5° Celsius) or sepsis
Complications
- Related to operative hysteroscopy or other surgical treatment
uterine perforation
postoperative hemorrhage, defined as excessive blood loss estimated or measured as ≥ 500 mL and/or need for blood transfusion
severe abdominal pain requiring analgesics excluding postoperative pain in the first 48 hours after hysteroscopic surgery
fluid overload (defined as absorption of more than 2500 mL of distention medium with clinical consequences for the patient)
electrolyte disturbances requiring treatment
gas embolism
Health related costs
the EQ-5D-5L and health-related costs based on physician visits, hospitalizations and emergency room visits are measured
Full Information
NCT ID
NCT04804332
First Posted
March 8, 2021
Last Updated
April 12, 2023
Sponsor
University Hospital, Ghent
Collaborators
Medtronic
1. Study Identification
Unique Protocol Identification Number
NCT04804332
Brief Title
Removal of Intrauterine Retained Products of Conception (RPOC) After Miscarriage Guided by Hysteroscopy Trial. A Randomized Controlled Trial.
Acronym
RIGHT
Official Title
Removal of Intrauterine Retained Products of Conception (RPOC) After Miscarriage Guided by Hysteroscopy Trial. A Randomized Controlled Trial.
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 12, 2021 (Actual)
Primary Completion Date
December 30, 2024 (Anticipated)
Study Completion Date
December 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Ghent
Collaborators
Medtronic
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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
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)
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
Cost-effectiveness objectives To compare the health related costs between operative hysteroscopy and expectant management.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Retained Products of Conception
Keywords
Retained Products of Conception, placental remnants, hysteroscopy, expectant management, fertility
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Design : RCT
Multicenter
Randomized controlled
Parallel group design
Superiority trial
Non-blinded
Masking
None (Open Label)
Allocation
Randomized
Enrollment
244 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
EXPECTANT MANAGEMENT
Arm Type
Experimental
Arm Description
No treatment will be offered.
Arm Title
OPERATIVE HYSTEROSCOPY
Arm Type
Experimental
Arm Description
Operative hysteroscopy using hysteroscopic morcellation (TruClearTM Hysteroscopic Tissue Removal System (Medtronic, Minneapolis, MN, USA)) is performed.
Intervention Type
Procedure
Intervention Name(s)
Operative hysteroscopy
Intervention Description
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
Other
Intervention Name(s)
Expectant management
Intervention Description
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.
Primary Outcome Measure Information:
Title
Time to next pregnancy
Description
The primary endpoint is the time until next pregnancy since randomization, with pregnancy defined as a positive urinary or serum hCG test. Patients are asked to contact the study team in case of pregnancy. If a participant has failed to contact the center, pregnancy will be asked at same time as the questionnaires and then once every 6 months as well as at the end of the study by telephone contact or e-mail.
Time Frame
up to 3 years after the start of the trial
Secondary Outcome Measure Information:
Title
Quality Of Life (QOL)
Description
measured by SF-36
Time Frame
at baseline, 8 weeks after randomization and 6 months after randomization
Title
Quality Of Life (QOL)
Description
measured by HADS (Hospital Anxiety and Depression Scale)
Time Frame
at baseline, 8 weeks after randomization and 6 months after randomization
Title
Quality Of Life (QOL)
Description
measured by EQ-5D-5L
Time Frame
at baseline, 8 weeks after randomization and 6 months after randomization
Title
Course of pregnancy
Description
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):
Time to conception, defined as the time from randomization to the date of conception retrospectively determined based on the crown-rump length measurement (CRL) by a first-trimester ultrasound.
Clinical pregnancy defined as a pregnancy diagnosed by ultrasonographic visualization of 1 or more gestational sacs or definitive clinical signs of pregnancy, including ectopic pregnancy. Multiple gestational sacs are counted as 1 clinical pregnancy.
Live birth, defined as the complete expulsion or extraction from the mother of a product of fertilization, irrespective of the duration of pregnancy, which after such separation breathes or shows any other evidence of life, such as heartbeat, umbilical cord pulsation, or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been
Time Frame
up to 3 years after the start of the trial
Title
Necessity for additional treatment
Description
Necessity for additional treatment
Time Frame
until 6 months after randomisation
Title
Out-of-protocol/unscheduled visits
Description
Re-interventions or additional treatment during the first 6 months including type, number and reasons.
Out-of-protocol visits to the outpatient clinic or general practitioner or hospitalizations including type, number, reasons and duration of hospitalization.
Time Frame
until 6 months after randomisation
Title
Complications
Description
Heavy uterine bleeding defined as uterine bleeding that needs acute intervention (IV iron administration, tranexamic acid or blood transfusion) on medical grounds
Time Frame
until 6 months after randomisation
Title
Complications
Description
Severe abdominal pain requiring analgesics or medical intervention, excluding postoperative pain in the first 48 hours after uterine surgery
Time Frame
until 6 months after randomisation
Title
Complications
Description
Fever (>38.5° Celsius) or sepsis
Time Frame
until 6 months after randomisation
Title
Complications
Description
- Related to operative hysteroscopy or other surgical treatment
uterine perforation
postoperative hemorrhage, defined as excessive blood loss estimated or measured as ≥ 500 mL and/or need for blood transfusion
severe abdominal pain requiring analgesics excluding postoperative pain in the first 48 hours after hysteroscopic surgery
fluid overload (defined as absorption of more than 2500 mL of distention medium with clinical consequences for the patient)
electrolyte disturbances requiring treatment
gas embolism
Time Frame
until 6 months after randomisation
Title
Health related costs
Description
the EQ-5D-5L and health-related costs based on physician visits, hospitalizations and emergency room visits are measured
Time Frame
until 6 months after randomisation
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
39 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eline Meireson
Phone
+3293327817
Email
eline.meireson@uzgent.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tjalina Hamerlynck, MD PhD
Organizational Affiliation
University Hospital, Ghent
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ghent University Hospital
City
Ghent
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eline Meireson, Msc
Phone
+3293327817
Email
eline.meireson@uzgent.be
First Name & Middle Initial & Last Name & Degree
Tjalina Hamerlynck, MD
12. IPD Sharing Statement
Plan to Share IPD
No
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Removal of Intrauterine Retained Products of Conception (RPOC) After Miscarriage Guided by Hysteroscopy Trial. A Randomized Controlled Trial.
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