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Trial registered on ANZCTR


Registration number
ACTRN12624001463561
Ethics application status
Approved
Date submitted
18/09/2024
Date registered
16/12/2024
Date last updated
16/12/2024
Date data sharing statement initially provided
16/12/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparing a 'wait and watch' approach vs medical treatment with misoprostol for first trimester retained products of pregnancy and using ultrasound to predict success
Scientific title
Comparison of misoprostol and conservative approach for managing first trimester retained products of conception and use of ultrasound to predict success– an open labelled randomized controlled trial
Secondary ID [1] 312930 0
nil known
Universal Trial Number (UTN)
U1111-1313-1154
Trial acronym
U-ROC trial – Ultrasound to predict success of misoprostol vs conservative approach for first trimester Retained products Of Conception
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Early pregnancy complication 335097 0
First trimester retained products of conception 335098 0
Condition category
Condition code
Reproductive Health and Childbirth 331599 331599 0 0
Fetal medicine and complications of pregnancy
Reproductive Health and Childbirth 332660 332660 0 0
Abortion

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients with first trimester symptomatic retained products of conception ( RPOC) and proven on transvaginal ultrasound after antecedent events of spontaneous miscarriage, primary medically managed miscarriage, primary dilatation and curettage(D&C) for miscarriage, medical termination of pregnancy and surgical termination of pregnancy with D&C will be randomized to either the control arm (expectant management, i.e., 'wait and watch') or the intervention arm ( medical management with misoprostol) in a 1:1 ratio. The randomization is stratified based on colour doppler scores of the retained tissue on transvaginal ultrasound; i.e., scores 1-4; 1- no vascularity, 2- minimal vascularity, 3- moderate vascularity, 4 - strong vascularity.

Intervention arm-
Medical management (Group M) – With this method, patients will be advised to self-administer misoprostol 800 mcg (4 tablets of 200 mcg) buccally (2 tablets kept in each cheek until dissolved, not to swallow) as a once only administration. To manage side effects, they will also be prescribed regular oral pantoprazole 40 mg once daily and 4 mg ondansetron wafers three times daily or as needed, oral ibuprofen 400 mg three times daily after meals or as needed, oral paracetamol 1000 mg upto 4 times daily or as needed, and oral panadeine forte 500/30 (2 tabs) upto 4 times daily or as needed for 24 hours. Patients will be counselled about side effects like nausea, vomiting, diarrhoea and strong uterine cramping and will be advised to keep a symptom diary of their side effects.
All patients will be advised about alert symptoms that should prompt a presentation to the nearest Emergency department including fever, foul-smelling discharge and heavy bleeding with clots with frequency of changing 1 full soaked pad every hour or less for over 4 hours.

Patients from both control and intervention arms will be followed up at 4 weeks ( Interim visit) and 8 weeks ( final visit) with a repeat transvaginal ultrasound at each visit to look for persistent retained products. At either visit, ultrasound findings of an empty uterus with absence of retained products defined as homogenous endometrium with absent vascularity with no measurable focus of hyperechoic material suggesting trophoblastic tissue will be considered successful management. These patients will not require subsequent clinic follow up. The persistence of retained products at 4 weeks will prompt a further follow up at 8 weeks to draw final conclusions. If RPOC is present on transvaginal ultrasound at 8 weeks, non-surgical management is considered unsuccessful and the patient is advised surgical management via hysteroscopic resection or ultrasound guided dilatation and curettage within 1 week. This will be arranged in our centre.

All participants will be consented at their baseline visit for a follow up phone call at 6 months to note long term sequelae of non surgical management of RPOC
Intervention code [1] 329534 0
Treatment: Drugs
Comparator / control treatment
Control arm - Expectant management (Group E) – There will be no intervention, or no medication will be given. They will be managed with a ‘wait and watch’ approach for a period of 8 weeks.

Patients from both control and intervention arms will be followed up at 4 weeks ( Interim visit) and 8 weeks ( final visit) with a repeat transvaginal ultrasound at each visit to look for persistent retained products. At either visit, ultrasound findings of an empty uterus with absence of retained products defined as homogenous endometrium with absent vascularity with no measurable focus of hyperechoic material suggesting trophoblastic tissue will be considered successful management. These patients will not require subsequent clinic follow up. The persistence of retained products at 4 weeks will prompt a further follow up at 8 weeks to draw final conclusions. If RPOC is present on transvaginal ultrasound at 8 weeks, non-surgical management is considered unsuccessful and the patient is advised surgical management via hysteroscopic resection or ultrasound guided dilatation and curettage within 1 week. This will be arranged in our centre.

All participants will be consented at their baseline visit for a follow up phone call at 6 months to note long term sequelae of non surgical management of RPOC
Control group
Active

Outcomes
Primary outcome [1] 339398 0
Success rates of expectant vs medical management for management of first trimester retained products of conception (RPOC)
Timepoint [1] 339398 0
4 weeks and 8 weeks ( primary timepoint) from baseline intervention and control arms
Secondary outcome [1] 439779 0
Volume of RPOC measured by transvaginal ultrasound ( TVS) and its influence on success or failure of intervention and control treatment arms
Timepoint [1] 439779 0
4 weeks and 8 weeks ( secondary timepoint) from baseline intervention and control arms
Secondary outcome [2] 440469 0
Colour doppler score ( CDS) 1-4 on TVS and its influence on success or failure of RPOC in the intervention and control arms
Timepoint [2] 440469 0
4 weeks and 8 weeks ( secondary timepoint) from baseline intervention and control arms
Secondary outcome [3] 440470 0
Composite secondary outcome of Uterine artery Resistance index ( RI) and pulsatile index ( PI) on TVS and its influence on success or failure of intervention and control arms
Timepoint [3] 440470 0
4 weeks and 8 weeks ( secondary timepoint) from baseline intervention and control arms

Eligibility
Key inclusion criteria
Transvaginal ultrasound scan showing the presence of a measurable focus of hyperechoic material within the endometrial cavity WITH any of the following will be considered for recruitment:
1. Symptomatic patients with moderate bleeding and/or pain presenting after 48 hours of antecedent events a-e:
a. Spontaneous miscarriage
b. Primary medical management of miscarriage - as per Mifemiso trial
c. Primary surgical D&C for miscarriage
d. Medical termination of pregnancy - MS-2 step ( name of product)
e. Surgical termination of pregnancy
2. Persistent spotting or light bleeding beyond 3 weeks from antecedent event
3. Positive urine B-HCG ( beta- human chorionic gonadotrophin) beyond 3 weeks from antecedent event
4. Amenorrhea beyond 6 weeks from antecedent event

There are no published grading systems for quantifying per vaginal blood loss during a miscarriage or termination and hence, for allowing for objective interpretation of symptomology, we have adopted a modified version of the pictographic scale by Higham et al. The frequency of pad use is based on experience.
a. Only red/brown spotting per vaginum
b. Light bleeding – changed every 4 hours or more
c. Moderate bleeding – changed every 4 hours or more
d. Heavy bleeding with clots (fully soaked pad)- change every 4 hours or less
Minimum age
16 Years
Maximum age
45 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Women who choose surgical management for proven retained products of conception (RPOC) on transvaginal ultrasound ( TVS)
2. Allergies/ contraindications to the use of misoprostol
3. Complete miscarriage on TVS or findings of uniform homogenous endometrium, with absence of vascularity and no measurable focus of hyperechoic material within the endometrial cavity or endocervical canal
4. TVS showing only presence of avascular blood clot and absence of trophoblastic tissue irrespective of symptoms – given the difficulty in distinguishing between avascular blood clot and avascular trophoblastic tissue, recruiters will take a 2nd opinion from fellow recruiters prior to inclusion/exclusion
5. Extrauterine pregnancy/ pregnancy of unknown location (PUL )
6. Intact gestational sac on ultrasound ( which suggests failed miscarriage and would require primary management)
7. Hemodynamic instability (severe vaginal haemorrhage) requiring immediate surgical intervention; Heavy bleeding with clots ( as defined by Higham et al) will also be excluded given the potential to lead to hemodynamic instability and will be considered for surgical management.
8. Presence of infection / sepsis (Temperature > 38 degree Celsius, tachycardia, offensive vaginal discharge)
9. Patients unable to consent

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomization - REDCap generated
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation ( computer sequence generated) used with stratification based on colour doppler scores 1-4
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Chi-square and proportion test as initial part of study is a pilot to calculate true sample size

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
18/12/2024
Actual
Date of last participant enrolment
Anticipated
30/11/2026
Actual
Date of last data collection
Anticipated
29/01/2027
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 27111 0
Nepean Hospital - Kingswood
Recruitment postcode(s) [1] 43189 0
2747 - Kingswood

Funding & Sponsors
Funding source category [1] 317362 0
Hospital
Name [1] 317362 0
Nepean Hospital
Country [1] 317362 0
Australia
Primary sponsor type
Hospital
Name
Nepean hospital
Address
Country
Australia
Secondary sponsor category [1] 319722 0
None
Name [1] 319722 0
Address [1] 319722 0
Country [1] 319722 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316094 0
Nepean Blue Mountains Local Health District
Ethics committee address [1] 316094 0
Ethics committee country [1] 316094 0
Australia
Date submitted for ethics approval [1] 316094 0
06/08/2024
Approval date [1] 316094 0
27/09/2024
Ethics approval number [1] 316094 0
2024/ETH01610

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 136758 0
Dr Caroline Mathias
Address 136758 0
Nepean Hospital, Somerset Street, Kingswood, NSW 2747
Country 136758 0
Australia
Phone 136758 0
+61 2 47344240
Fax 136758 0
Email 136758 0
caroline.mathias@health.nsw.gov.au
Contact person for public queries
Name 136759 0
Caroline Mathias
Address 136759 0
Nepean Hospital, Somerset Street, Kingswood, NSW 2747
Country 136759 0
Australia
Phone 136759 0
+61 2 47344240
Fax 136759 0
Email 136759 0
caroline.mathias@health.nsw.gov.au
Contact person for scientific queries
Name 136760 0
Caroline Mathias
Address 136760 0
Nepean Hospital, Somerset Street, Kingswood, NSW 2747
Country 136760 0
Australia
Phone 136760 0
+61 2 47344240
Fax 136760 0
Email 136760 0
caroline.mathias@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.