MISOPROSTOL FOR THE TREATMENT OF SUSPECTED POSTPARTUM RETAINED PRODUCTS OF CONCEPTION

MISOPROSTOL FOR THE TREATMENT OF SUSPECTED POSTPARTUM RETAINED PRODUCTS OF CONCEPTION - A RANDOMIZED TRIAL

The goal of this current study is to evaluate the efficacy of treatment of postpartum patients with suspected retained products of conception (RPOC) with Misoprostol in reducing the frequency of postpartum RPOC compared to a control group of patients that will be managed expectantly, in a prospective randomized trial.

Study Overview

• Status: Recruiting
• Conditions: Retained Products of Conception
• Intervention / Treatment: Drug: Misoprostol 200mcg Tab

Detailed Description

Misoprostol (Cytotec) is used widely in Obstetrics and Gynecology, whether for labor induction (1), prevention (2), and treatment (3) of early postpartum hemorrhage (ePPH), induced and missed abortions (4) and for cases suspected for having retained products of conception postabortion and postpartum (RPOC, residua).

While it has been shown in previous studies that misoprostol is efficacious for most of the above-mentioned indications, it is less well-established that the treatment for suspected postpartum RPOC alters the natural course of events and reduces the number of patients requiring surgical intervention and actually having RPOC.

RPOC is estimated to complicate about 1% of term pregnancies and is more prevalent than after miscarriages and termination of pregnancy (5).

The diagnosis and treatment of RPOC might be challenging, as there are no clearly determined diagnostic criteria, evidence-based guidelines or treatment protocols (6).

Different protocols for the follow-up and treatment of cases suspected of RPOC are in use worldwide, including expectant management, administrating uterotonics, performing suction curettage (6), and performing hysteroscopy (7, 8). Evidence in the literature supports the treatment of RPOC with operative hysteroscopy since curettage seems to increase the risk for intrauterine adhesions and Asherman syndrome (9, 10) with the possibility for menstrual abnormalities, infertility or subfertility, recurrent pregnancy losses, preterm labor, and preterm premature rupture of membranes (11).

Chambers et al published in 2009 a 6-year trial (12), which shows that treatment with 200 mcg SL / PO misoprostol 3 times daily for 2 days may effectively treat RPOC and reduce repeat curettage rate by 79.6%. There was also the complete resolution of symptoms in 93%, and 77% of women reported a high level of satisfaction. The trial was retrospective and RPOC was not confirmed by hysteroscopy or histology.

The main tool for diagnosis and follow-up in cases of RPOC is postpartum ultrasound, showing low, medium, and high probability for residua, with the clinical symptoms of abnormal bleeding pattern, abdominal tenderness, and persistently dilated cervix.

We've decided to set the categories according to the study by Smorgick (13), although we chose to name them and treat them differently. The categories are:

1. Low probability for residua - ultrasound shows thin regular endometrial line 10 mm and below, with no intrauterine mass or Doppler vascular flow.

   In effect a normal ultrasound scan.

2. Medium probability for residua - ultrasound shows a cavity over 10 mm, intrauterine hypo / hyperechogenic mass, or irregular endometrial line without Doppler flow. With this group, PROC cannot be excluded.
3. High probability for residua - with the addition of Doppler vascular flow to the cavity.

The natural course of the ultrasonic appearance of the uterine cavity postpartum (14) was shown to take roughly 56 days for the cavity to appear empty in 95% percent of cases not suspected of having RPOC.

This study aims to test prospectively expectant management compared to misoprostol administration for a certain duration of time of cases with risk factors for RPOC, including cases undergoing revision of the uterine cavity or manual lysis of placenta postpartum, early postpartum hemorrhage, cases with a history of treated postpartum residua, having placental pathology (succenturiate, bilobed placenta), a pregnancy that started as multifetal with only one fetus reached advanced pregnancy, and patients undergoing Bumm curettage post-delivery.

2. Aims Since the literature data on this subject is scarce and the treatment is challenging, the primary aim of this study is to assess prospectively and randomly expectant management vs. misoprostol administration (PV, PO, SL) on the treatment for suspected RPOC postpartum in women with risk factors for residua along an 8-week duration as characterized by ultrasound follow-up every 2-3 weeks and divided to a 3 tier system of the low, medium and high probability of residua and the cases requiring hysteroscopy for suspected residua.

Secondary aims include side effects of treatment, late postpartum hemorrhage, blood transfusion, and endomyometritis / PID and complications.

3. Hypothesis In this study, we hypothesize that the treatment with misoprostol, compared to expectant management, will be able to reduce the number of cases at medium and high probability of residua as described by ultrasound and by that reduce the number of cases requiring hysteroscopy and treatment of residua.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Oshri Barel, MD; Phone Number: +972559382117; Email: oshrib@assuta.co.il
• Study Contact Backup: Name: Irad Burshtein, MD; Phone Number: +972537345127; Email: iradb@assuta.co.il

Study Locations

• Israel
  • Ashdod, Israel
    • Recruiting
    • Assuta Ashdod University Hospital
    • Contact: Oshri Barel, MD; Phone Number: +972559382117; Email: oshrib@assuta.co.il
    • Principal Investigator: oshri Barel, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Women between the ages of 18 years - 45 years.
• Spontaneous vaginal delivery or vacuum extraction, including VBAC cases
• Revision of the uterine cavity or manual lysis of the placenta postpartum
• Early postpartum hemorrhage
• Cases with a history of treated postpartum residua (by curettage or hysteroscopy)
• Placental pathology (succenturiate placenta, bilobed placenta)
• Pregnancy that started as a multifetal gestation with only one fetus reached advanced pregnancy
• Bumm curettage post-delivery
• Patients are able to provide written consent

Exclusion Criteria:

• Patients with no risk factors of RPOC
• Cesarean section on index pregnancy
• Cases requiring urgent curettage for late postpartum hemorrhage
• Inability to consent due to cognitive or language barrier

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; The intervention group will include patients with suspected postpartum RPOC that will receive treatment with Misoprostol, 600 microgram SL/PO/PV	Drug: Misoprostol 200mcg Tab; Patients in the intervention group with suspected postpartum RPOC will receive 600 micrograms of misoprostol up to 3 times following delivery and followed up by ultrasound and clinical examinations for 6-12 weeks post-partum
No Intervention: Control group; The control group will include women with suspected postpartum RPOC per ultrasound examination that will undergo conservative follow-up with ultrasound for a period of 6-12 weeks postpartum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cases of retained products of conception	The primary endpoint will be the number of patients with histopathology-proven retained products of conception at 8-16 weeks postpartum in each group.	8-16 weeks postpartum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for hysteroscopy due to suspected RPOC	number of hysteroscopies in each group	8-16 weeks postpartum
side effects of treatment	any side effects of treatments with Misoprostol	8-16 weeks postpartum
Late postpartum hemorrhage	Late postpartum hemorrhage during the followup	6 weeks postpartum
Blood transfusions	The need of blood transfusion during the followup	6-18 weeks postpartum
endomyometritis / PID	any events of endomyometritis / PID postpartum	6-18 weeks postpartum
Re-admissions to the hospital	cases that required re-admission to the hospital after discharge from tyhe postpartum ward.	up to 18 weeks

Collaborators and Investigators

• Sponsor: Assuta Ashdod Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: August 20, 2023
• First Submitted That Met QC Criteria: August 20, 2023
• First Posted (Actual): August 24, 2023

Study Record Updates

• Last Update Posted (Actual): August 24, 2023
• Last Update Submitted That Met QC Criteria: August 20, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Gastrointestinal Agents; Reproductive Control Agents; Anti-Ulcer Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Misoprostol
• Other Study ID Numbers: 000621AAA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No