The HYsteroscopic Miscarriage MaNagement Trial: A Pilot RCT Investigating a Novel Management Pathway for RPOC

NCT04751500 | Completed DMC

• 2 other identifiers: 27690920/WM/0287
• Study Type: interventional
• Target: 149
• Locations: 1 country
• Sites: 1

Brief Summary

Pregnancy tissue can be found remaining in the womb in up to 20% of women following a miscarriage. These "retained products of conception" (RPOC), which are diagnosed by transvaginal ultrasound, can cause prolonged bleeding, pain, infection, impaired fertility and therefore further psychological distress. Ineffective medical and surgical interventions place considerable burden on affected women and utilise scarce health care resources. Additionally, surgery is performed 'blindly' using a suction tube or metal curette where risks include perforation of the womb and scarring of the womb lining, both of which lead to delayed fertility and in the worst circumstances, infertility. There is no current guidance on how to best investigate and manage RPOC. New surgical equipment allows RPOC removal under vision, using a specially designed telescope placed inside the womb (hysteroscopy). This precise technique may more successfully and less traumatically remove RPOC, minimising ongoing bleeding, the risk of womb perforation and scar tissue formation, thereby reducing the risk of infertility. The investigators propose a pilot randomised controlled trial using routine transvaginal ultrasound to diagnose RPOC in women who choose non-surgical management of a first-trimester (≤14 weeks) miscarriage. This scan will be done 8 weeks post-miscarriage diagnosis. Women who have RPOC on this scan will be randomised (in a 1:1 ratio) to receive outpatient hysteroscopy ('OPH') or 'standard treatment' (expectant, medical, surgical and/or antibiotic treatment). Women who had RPOC will be followed-up at 14 weeks after randomisation to explore clinical outcomes (symptoms, quality of life) and use of additional healthcare resources (e.g. additional investigations / treatments / hospitalisations). All patients, no matter whether they were diagnosed with RPOC or not, will be followed up at 26 weeks and 52 weeks after randomisation/ultrasound scan to determine clinical pregnancy rates and pregnancy outcomes. All patients who have had a miscarriage or have not fallen pregnant since entering the trial will be offered a hysteroscopy to see if there are any conditions affecting the womb lining which may be contributing to pregnancy failure.

Conditions

Retained Products After Miscarriage

Keywords

ultrasound; hysteroscopy; miscarriage; retained products of conception

Outcome Measures

Primary Outcomes (11)

• Number of eligible patients

  The number of patients approached that fulfill the eligibility criteria for entry into the trial

  During recruitment - 6 months

• Proportion of patients enrolled into the trial

  The proportion of eligible women that agree to participate in the trial

  During recruitment - 6 months

• Proportion of patients attending scan

  The proportion of women that attended the hospital for their 8-week post-miscarriage ultrasound scan

  At ultrasound scan 8 weeks post-miscarriage diagnosis

• Proportion of patients attending outpatient hysteroscopy (if randomised to this treatment)

  Of the women randomised to hysteroscopic treatment of RPOC, the proportion that attended their appointment

  During outpatient hysteroscopy (if randomised to this treatment)

• Proportion of patients attending 14-week follow-up

  The proportion of women that attended follow-up at 14 weeks

  14-week follow up

• Proportion of patients attending 26-week follow-up

  The proportion of women that attended follow-up at 26 weeks

  26-week follow up

• Proportion of patients attending 52-week follow-up

  The proportion of women that attended follow-up at 52 weeks

  52-week follow up

• Acceptability of trial to eligible women

  To determine why patients decline participation into the trial or withdraw after consent

  Up to 8 months

• Acceptability of ultrasound scan to patients

  Acceptability of ultrasound scan to patients as recorded on a questionnaire given to the woman after their ultrasound scan on a 5-point Likert scale

  At ultrasound scan 8 weeks post-miscarriage diagnosis

• Acceptability of outpatient hysteroscopy to patients

  Acceptability of outpatient hysteroscopy to patients, if randomised to this treatment, as recorded on a questionnaire given to the woman after their hysteroscopy on a 5-point Likert scale

  During outpatient hysteroscopy (if randomised to this treatment)

• Robustness of data collection tools

  Assessing the completion of the patient and clinician questionnaires during the course of the study to determine how robust/appropriate the data collection tools are (we would expect at least 90% of the forms to be filled out)

  From recruitment of first patient to end of trial (up to 20 months)

Secondary Outcomes (14)

• Clinical pregnancy rates

  Assessed at 26 and 52 weeks post-randomisation/ultrasound scan

• Time to next pregnancy

  Assessed at 26 and 52 weeks post-randomisation/ultrasound scan

• Symptoms

  14 weeks post-randomisation/ultrasound scan

• Impact on quality of life

  14 weeks post-randomisation/ultrasound scan

• Impact on work

  14 weeks post-randomisation/ultrasound scan

Study Arms (2)

Outpatient Hysteroscopy

EXPERIMENTAL

Outpatient hysteroscopic morcellation of retained products of conception

Procedure: Outpatient hysteroscopy

Standard Treatment

ACTIVE COMPARATOR

Standard treatment of retained products of conception in the form of expectant management, medical management, antibiotic therapy and/or surgical management (manual vacuum aspiration/suction curettage/dilatation and curettage)

Behavioral: Expectant management; Drug: Medical management; Drug: Antibiotic; Procedure: Surgical management

Interventions

Outpatient hysteroscopy PROCEDURE

Direct visualisation and careful extraction of retained pregnancy tissue using a specific hysteroscopic technology known as a hysteroscopic tissue retrieval system.

Outpatient Hysteroscopy

Expectant management BEHAVIORAL

Leaving the retained pregnancy tissue alone to pass by itself

Standard Treatment

Medical management DRUG

Giving medications to contract the womb to pass the retained pregnancy tissue

Also known as: misoprostol, mifepristone

Standard Treatment

Antibiotic DRUG

Giving antibiotics to reduce any inflammation/infection caused by the retained pregnancy tissue allowing it to pass by itself

Also known as: Augmentin, Co-amoxiclav, Metronidazole, Clindamycin

Standard Treatment

Surgical management PROCEDURE

Passing a small cannula/catheter/currette into the womb and mechanically scraping the womb lining to remove the retained pregnancy tissue

Also known as: manual vacuum aspiration, suction evacuation of the uterus, dilatation and currettage

Standard Treatment

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women above 18 years
• Women choosing either expectant or medical management of a first-trimester miscarriage ≤14 weeks gestation
• Women wanting to conceive as soon as possible after their miscarriage
• Consent to trial processes: (1) undergo follow-up with transvaginal ultrasound for the investigation of RPOC; (2) be randomised to outpatient hysteroscopy for confirmation and treatment or standard management; (3) accept trial follow up procedures - questionnaires, telephone interviews

You may not qualify if:

• Women below 18 years
• Women with findings suspicious of gestational trophoblastic disease
• Women with fever (≥38°C) or sepsis secondary to genital tract infection/endometritis
• Women who are unable to understand spoken and written English

Sponsors & Collaborators

• Birmingham Women's and Children's NHS Foundation Trust: lead
• Tommy's: collaborator

Study Sites (1)

Birmingham Women's Hospital

Birmingham, B15 2TG, United Kingdom

Location

MeSH Terms

Conditions

Abortion, Incomplete; Abortion, Spontaneous

Interventions

Watchful Waiting; Practice Management, Medical; Misoprostol; Mifepristone; Anti-Bacterial Agents; Amoxicillin-Potassium Clavulanate Combination; Metronidazole; Clindamycin; Dilatation

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Practice Management; Professional Practice; Organization and Administration; Prostaglandins E, Synthetic; Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Clavulanic Acid; Clavulanic Acids; beta-Lactams; Lactams; Amides; Organic Chemicals; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Lincomycin; Lincosamides; Pyrrolidines; Glycosides; Carbohydrates; Investigative Techniques

Study Officials

• T Justin Clark, FRCOG

  Birmingham Women's NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study involves two phases: 1) All recruited women will be scanned for RPOC at 8 weeks post-miscarriage diagnosis. 2) Women that have RPOC on this scan will then be randomised in a 1:1 manner to either outpatient hysteroscopy or standard treatment.

Study Record Dates

• First Submitted: January 29, 2021
• First Posted: February 12, 2021
• Study Start: January 31, 2021
• Primary Completion: November 2, 2022
• Study Completion: November 2, 2022
• Last Updated: August 14, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)