xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06009679</url>
    </required_header>
    <id_info>
      <org_study_id>000621AAA</org_study_id>
      <nct_id>NCT06009679</nct_id>
    </id_info>
    <brief_title>MISOPROSTOL FOR THE TREATMENT OF SUSPECTED POSTPARTUM RETAINED PRODUCTS OF CONCEPTION</brief_title>
    <official_title>MISOPROSTOL FOR THE TREATMENT OF SUSPECTED POSTPARTUM RETAINED PRODUCTS OF CONCEPTION - A RANDOMIZED TRIAL</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Assuta Ashdod Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Assuta Ashdod Hospital</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this current study is to evaluate the efficacy of treatment of postpartum&#xD;
        patients with suspected retained products of conception (RPOC) with Misoprostol in reducing&#xD;
        the frequency of postpartum RPOC compared to a control group of patients that will be managed&#xD;
        expectantly, in a prospective randomized trial.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Misoprostol (Cytotec) is used widely in Obstetrics and Gynecology, whether for labor&#xD;
        induction (1), prevention (2), and treatment (3) of early postpartum hemorrhage (ePPH),&#xD;
        induced and missed abortions (4) and for cases suspected for having retained products of&#xD;
        conception postabortion and postpartum (RPOC, residua).&#xD;
  &#xD;
        While it has been shown in previous studies that misoprostol is efficacious for most of the&#xD;
        above-mentioned indications, it is less well-established that the treatment for suspected&#xD;
        postpartum RPOC alters the natural course of events and reduces the number of patients&#xD;
        requiring surgical intervention and actually having RPOC.&#xD;
  &#xD;
        RPOC is estimated to complicate about 1% of term pregnancies and is more prevalent than after&#xD;
        miscarriages and termination of pregnancy (5).&#xD;
  &#xD;
        The diagnosis and treatment of RPOC might be challenging, as there are no clearly determined&#xD;
        diagnostic criteria, evidence-based guidelines or treatment protocols (6).&#xD;
  &#xD;
        Different protocols for the follow-up and treatment of cases suspected of RPOC are in use&#xD;
        worldwide, including expectant management, administrating uterotonics, performing suction&#xD;
        curettage (6), and performing hysteroscopy (7, 8). Evidence in the literature supports the&#xD;
        treatment of RPOC with operative hysteroscopy since curettage seems to increase the risk for&#xD;
        intrauterine adhesions and Asherman syndrome (9, 10) with the possibility for menstrual&#xD;
        abnormalities, infertility or subfertility, recurrent pregnancy losses, preterm labor, and&#xD;
        preterm premature rupture of membranes (11).&#xD;
  &#xD;
        Chambers et al published in 2009 a 6-year trial (12), which shows that treatment with 200 mcg&#xD;
        SL / PO misoprostol 3 times daily for 2 days may effectively treat RPOC and reduce repeat&#xD;
        curettage rate by 79.6%. There was also the complete resolution of symptoms in 93%, and 77%&#xD;
        of women reported a high level of satisfaction. The trial was retrospective and RPOC was not&#xD;
        confirmed by hysteroscopy or histology.&#xD;
  &#xD;
        The main tool for diagnosis and follow-up in cases of RPOC is postpartum ultrasound, showing&#xD;
        low, medium, and high probability for residua, with the clinical symptoms of abnormal&#xD;
        bleeding pattern, abdominal tenderness, and persistently dilated cervix.&#xD;
  &#xD;
        We've decided to set the categories according to the study by Smorgick (13), although we&#xD;
        chose to name them and treat them differently. The categories are:&#xD;
  &#xD;
          1. Low probability for residua - ultrasound shows thin regular endometrial line 10 mm and&#xD;
             below, with no intrauterine mass or Doppler vascular flow.&#xD;
  &#xD;
             In effect a normal ultrasound scan.&#xD;
  &#xD;
          2. Medium probability for residua - ultrasound shows a cavity over 10 mm, intrauterine hypo&#xD;
             / hyperechogenic mass, or irregular endometrial line without Doppler flow. With this&#xD;
             group, PROC cannot be excluded.&#xD;
  &#xD;
          3. High probability for residua - with the addition of Doppler vascular flow to the cavity.&#xD;
  &#xD;
        The natural course of the ultrasonic appearance of the uterine cavity postpartum (14) was&#xD;
        shown to take roughly 56 days for the cavity to appear empty in 95% percent of cases not&#xD;
        suspected of having RPOC.&#xD;
  &#xD;
        This study aims to test prospectively expectant management compared to misoprostol&#xD;
        administration for a certain duration of time of cases with risk factors for RPOC, including&#xD;
        cases undergoing revision of the uterine cavity or manual lysis of placenta postpartum, early&#xD;
        postpartum hemorrhage, cases with a history of treated postpartum residua, having placental&#xD;
        pathology (succenturiate, bilobed placenta), a pregnancy that started as multifetal with only&#xD;
        one fetus reached advanced pregnancy, and patients undergoing Bumm curettage post-delivery.&#xD;
  &#xD;
        2. Aims Since the literature data on this subject is scarce and the treatment is challenging,&#xD;
        the primary aim of this study is to assess prospectively and randomly expectant management&#xD;
        vs. misoprostol administration (PV, PO, SL) on the treatment for suspected RPOC postpartum in&#xD;
        women with risk factors for residua along an 8-week duration as characterized by ultrasound&#xD;
        follow-up every 2-3 weeks and divided to a 3 tier system of the low, medium and high&#xD;
        probability of residua and the cases requiring hysteroscopy for suspected residua.&#xD;
  &#xD;
        Secondary aims include side effects of treatment, late postpartum hemorrhage, blood&#xD;
        transfusion, and endomyometritis / PID and complications.&#xD;
  &#xD;
        3. Hypothesis In this study, we hypothesize that the treatment with misoprostol, compared to&#xD;
        expectant management, will be able to reduce the number of cases at medium and high&#xD;
        probability of residua as described by ultrasound and by that reduce the number of cases&#xD;
        requiring hysteroscopy and treatment of residua.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">February 2, 2021</start_date>
    <completion_date type="Anticipated">June 30, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Two arms: the intervention groups will include patients with suspected postpartum RPOC that will receive treatment with Misoprostol, and the control group will undergo conservative follow-up with ultrasound. The primary endpoint will be the number of patients with histopathology-proven retained products of conception at 8-16 weeks postpartum in each group. secondary endpoints will be the number of hysteroscopies in each group, side effects of treatment, late postpartum hemorrhage, blood transfusion, endomyometritis / PID and re-admissions to the hospital in each group.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Cases of retained products of conception</measure>
      <time_frame>8-16 weeks postpartum</time_frame>
      <description>The primary endpoint will be the number of patients with histopathology-proven retained products of conception at 8-16 weeks postpartum in each group.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Need for hysteroscopy due to suspected RPOC</measure>
      <time_frame>8-16 weeks postpartum</time_frame>
      <description>number of hysteroscopies in each group</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>side effects of treatment</measure>
      <time_frame>8-16 weeks postpartum</time_frame>
      <description>any side effects of treatments with Misoprostol</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Late postpartum hemorrhage</measure>
      <time_frame>6 weeks postpartum</time_frame>
      <description>Late postpartum hemorrhage during the followup</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood transfusions</measure>
      <time_frame>6-18 weeks postpartum</time_frame>
      <description>The need of blood transfusion during the followup</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>endomyometritis / PID</measure>
      <time_frame>6-18 weeks postpartum</time_frame>
      <description>any events of endomyometritis / PID postpartum</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Re-admissions to the hospital</measure>
      <time_frame>up to 18 weeks</time_frame>
      <description>cases that required re-admission to the hospital after discharge from tyhe postpartum ward.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">150</enrollment>
    <condition>Retained Products of Conception</condition>
    <arm_group>
      <arm_group_label>Intervention group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The intervention group will include patients with suspected postpartum RPOC that will receive treatment with Misoprostol, 600 microgram SL/PO/PV</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>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</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Misoprostol 200mcg Tab</intervention_name>
      <description>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</description>
      <arm_group_label>Intervention group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Women between the ages of 18 years - 45 years.&#xD;
  &#xD;
            -  Spontaneous vaginal delivery or vacuum extraction, including VBAC cases&#xD;
  &#xD;
            -  Revision of the uterine cavity or manual lysis of the placenta postpartum&#xD;
  &#xD;
            -  Early postpartum hemorrhage&#xD;
  &#xD;
            -  Cases with a history of treated postpartum residua (by curettage or hysteroscopy)&#xD;
  &#xD;
            -  Placental pathology (succenturiate placenta, bilobed placenta)&#xD;
  &#xD;
            -  Pregnancy that started as a multifetal gestation with only one fetus reached advanced&#xD;
               pregnancy&#xD;
  &#xD;
            -  Bumm curettage post-delivery&#xD;
  &#xD;
            -  Patients are able to provide written consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients with no risk factors of RPOC&#xD;
  &#xD;
            -  Cesarean section on index pregnancy&#xD;
  &#xD;
            -  Cases requiring urgent curettage for late postpartum hemorrhage&#xD;
  &#xD;
            -  Inability to consent due to cognitive or language barrier&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>45 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>oshri Barel, MD</last_name>
      <phone>+972559382117</phone>
      <email>oshrib@assuta.co.il</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Irad Burshtein, MD</last_name>
      <phone>+972537345127</phone>
      <email>iradb@assuta.co.il</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Assuta Ashdod University Hospital</name>
        <address>
          <city>Ashdod</city>
          <country>Israel</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Oshri Barel, MD</last_name>
        <phone>+972559382117</phone>
        <email>oshrib@assuta.co.il</email>
      </contact>
      <investigator>
        <last_name>Oshri Barel, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Israel</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 20, 2023</study_first_submitted>
    <study_first_submitted_qc>August 20, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 24, 2023</study_first_posted>
    <last_update_submitted>August 20, 2023</last_update_submitted>
    <last_update_submitted_qc>August 20, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 24, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Assuta Ashdod Hospital</investigator_affiliation>
      <investigator_full_name>Oshri Barell</investigator_full_name>
      <investigator_title>DR OSHRI BAREL</investigator_title>
    </responsible_party>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Misoprostol</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06009679
  org study id: 000621AAA
  nct id: NCT06009679
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  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.
  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.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Two arms: the intervention groups will include patients with suspected postpartum RPOC that will receive treatment with Misoprostol, and the control group will undergo conservative follow-up with ultrasound. The primary endpoint will be the number of patients with histopathology-proven retained products of conception at 8-16 weeks postpartum in each group. secondary endpoints will be the number of hysteroscopies in each group, side effects of treatment, late postpartum hemorrhage, blood transfusion, endomyometritis / PID and re-admissions to the hospital in each group.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Cases of retained products of conception
  time frame: 8-16 weeks postpartum
  description: The primary endpoint will be the number of patients with histopathology-proven retained products of conception at 8-16 weeks postpartum in each group.
  measure: Need for hysteroscopy due to suspected RPOC
  time frame: 8-16 weeks postpartum
  description: number of hysteroscopies in each group
  measure: side effects of treatment
  time frame: 8-16 weeks postpartum
  description: any side effects of treatments with Misoprostol
  measure: Late postpartum hemorrhage
  time frame: 6 weeks postpartum
  description: Late postpartum hemorrhage during the followup
  measure: Blood transfusions
  time frame: 6-18 weeks postpartum
  description: The need of blood transfusion during the followup
  measure: endomyometritis / PID
  time frame: 6-18 weeks postpartum
  description: any events of endomyometritis / PID postpartum
  measure: Re-admissions to the hospital
  time frame: up to 18 weeks
  description: cases that required re-admission to the hospital after discharge from tyhe postpartum ward.
  arm group label: Intervention group
  arm group type: Experimental
  description: The intervention group will include patients with suspected postpartum RPOC that will receive treatment with Misoprostol, 600 microgram SL/PO/PV
  arm group label: Control group
  arm group type: No Intervention
  description: 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
  intervention type: Drug
  intervention name: Misoprostol 200mcg Tab
  description: 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
  arm group label: Intervention group
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: 45 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: oshri Barel, MD
  phone: +972559382117
  email: oshrib@assuta.co.il
  last name: Irad Burshtein, MD
  phone: +972537345127
  email: iradb@assuta.co.il
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  country: Israel
  responsible party type: Principal Investigator
  investigator affiliation: Assuta Ashdod Hospital
  investigator full name: Oshri Barell
  investigator title: DR OSHRI BAREL
  mesh term: Misoprostol
  sharing ipd: No