<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/NCT03755531</url>
  </required_header>
  <id_info>
    <org_study_id>4 Al-KindyCM</org_study_id>
    <nct_id>NCT03755531</nct_id>
  </id_info>
  <brief_title>Carbetocin Versus Oxytocin for the Prevention of Postpartum Hemorrhage in Emergency Caesarean Delivery</brief_title>
  <official_title>Heat Stable Carbetocin Versus Oxytocin for the Prevention of Primary Postpartum Hemorrhage in Emergency Caesarean Delivery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Al-Kindy College of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Elweyia Maternity Teaching Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Al-Kindy College of Medicine</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Postpartum haemorrhage keeps to be the leading cause of maternal mortality in middle and&#xD;
      low-income countries, including Iraq. Much advancement had been made in the field of&#xD;
      treatment for postpartum haemorrhage but no much progress had been made in the field of&#xD;
      prevention, where one of its main component is the administration of uterotonic, preferably&#xD;
      oxytocin, immediately after birth of the baby.&#xD;
&#xD;
      In many low- and middle income countries, the efficacy of oxytocin cannot be assured since&#xD;
      access to sustained cold-chain is unavailable. Regarding the other uterotonics; ergometrine&#xD;
      degrades when exposed to heat or light. Misoprostol degrades rapidly when exposed to&#xD;
      Moisture.&#xD;
&#xD;
      Innovation in the manufacture of carbetocin had meet the stability requirements for hot and&#xD;
      humid climates.&#xD;
&#xD;
      This study had been accomplished to evaluate the uterotonic effect of carbetocin compared&#xD;
      with oxytocin for the prevention of postpartum haemorrhage in emergency caesarean delivery.&#xD;
      Looking if carbetocin is superior to oxytocin in term of reduction in the need for additional&#xD;
      uterotonic agents or the occurrence of PPH.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Setting and design:&#xD;
&#xD;
      It is a double blinded randomized parallel clinical trial. That had been conducted at Al&#xD;
      Elweyia Maternity Teaching Hospital in Baghdad during the period from Jan., 4th, 2018 to&#xD;
      August, 1st, 2018. Written consent was insured for all the participants.&#xD;
&#xD;
      Data collection:&#xD;
&#xD;
      Three hundred and twenty pregnant women who were underwent emergency caesarean sections under&#xD;
      regional anesthesia were enrolled in the study (due to limitation of carbetocin ampoules that&#xD;
      were available). Those women were randomized to oxytocin or carbetocin in a rate of 2:1 (for&#xD;
      prophylaxis of PPH in the active management of third stage of labour). Twenty cases were&#xD;
      omitted since they were not fulfilled the eligibility criteria and only three hundred women&#xD;
      were completed the study. They were divided into two groups:&#xD;
&#xD;
      Group1 (case group): 100 pregnant women, whom they received carbetocin for the prevention of&#xD;
      PPH.&#xD;
&#xD;
      Group 2 (control group): 200 pregnant women, whom they received oxytocin for the prevention&#xD;
      of PPH.&#xD;
&#xD;
      Additional information including age, parity, past medical history, and body mass index (BMI)&#xD;
      were taken.&#xD;
&#xD;
      Intervention:&#xD;
&#xD;
      The following steps were followed:&#xD;
&#xD;
        1. Hemoglobin and hematocrit were assessed before caesarean section.&#xD;
&#xD;
        2. One ml of either carbitocin (100 mcg) or oxytocin (10 IU) was given as a bolus&#xD;
           intravenous injection by the anesthesiologist after labor of the baby at once.&#xD;
&#xD;
        3. The placentae were delivered by controlled cord traction.&#xD;
&#xD;
        4. It was the operating obstetrician decision to evaluated the uterine tone, bleeding&#xD;
           intra-operatively and the need for an additional uterotonic and method of its&#xD;
           administration, dose and duration.&#xD;
&#xD;
        5. Our center usual regimen for uterine atony is an oxytocin (40 IU in 500 ml isotonic&#xD;
           crystalloid solution) intravenous infusion over 4-5 hours.&#xD;
&#xD;
      Follow up:&#xD;
&#xD;
      For 24 hours was done, that is include:&#xD;
&#xD;
        1. Evaluation of blood loss by the obstetrician and the anesthesiologist after skin&#xD;
           closure, that is include the entire amount that had been suctioned, taken by the&#xD;
           surgical gauzes or spilled in the surgical field, using visual estimation chart for&#xD;
           assessment of blood loss.&#xD;
&#xD;
        2. The need of any additional uterotonic drugs after the operation was recorded.&#xD;
&#xD;
        3. The need of blood transfusion post delivery.&#xD;
&#xD;
        4. The blood pressure and pulse rate of the women involved in the study were documented at&#xD;
           0, 5, 10, 20, 30 and 60 minutes after the injection of the drug.&#xD;
&#xD;
        5. The period of operation (skin cut into the final closure of the skin) was recorded.&#xD;
&#xD;
        6. Intravenous fluid infusion was administered regularly and as it had been stated by the&#xD;
           obstetricians and maintained after the operation until oral intake was started.&#xD;
&#xD;
        7. Hemoglobin and hematocrit was assessed the day after the caesarean section.&#xD;
&#xD;
      Statistical analysis:&#xD;
&#xD;
      Statistical Package for Social Sciences (SPSS) version 21 was used. Descriptive statistics&#xD;
      presented as (mean ± standard deviation) and frequencies as percentages. The database was&#xD;
      examined for errors using range and logical data cleaning methods, and inconsistencies were&#xD;
      remedied. Chi square test was used to compare between categorical variables (Fishers exact&#xD;
      test used when expected variable was less than 20% of total) and t-test was used to compare&#xD;
      between two means. Cohen's d, a standardized measure of effect size for difference between 2&#xD;
      means, which can be compared across different variables and studies, since it has no unit of&#xD;
      measurement was used. Significance level was set at P &lt; 0.05.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 4, 2018</start_date>
  <completion_date type="Actual">August 1, 2018</completion_date>
  <primary_completion_date type="Actual">June 10, 2018</primary_completion_date>
  <phase>Phase 4</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>Parallel Assignment</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>The anesthetist was the person in charge for giving the allocated drug after labor of the baby at once. Otherwise the operating obstetricians, the care givers, investigators and the ouctcomes assessor were all blinded to the type of the injection.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Blood loss equal or more than 1000 ml</measure>
    <time_frame>During the first 24 hours</time_frame>
    <description>Proportion of women with blood loss equal or more than 1000 ml in both study groups</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Use of additional uterotonics</measure>
    <time_frame>During the first 24 hours</time_frame>
    <description>Proportion of the women whom they need additional uterotonic agents</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Blood pressure changes in carbetocin versus oxytocin group</measure>
    <time_frame>Within one hour after administration of the drugs</time_frame>
    <description>Systolic and diastolic blood pressure changes that may occur in both groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulse rate changes in carbetocin versus oxytocin group</measure>
    <time_frame>Within one hour after administration of the drugs</time_frame>
    <description>Detection of pulse rate changes that may occur in both groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood transfusion need</measure>
    <time_frame>During the first 24 hours</time_frame>
    <description>Proportion of the women whom they need blood transfusion</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">300</enrollment>
  <condition>Postpartum Hemorrhage (Primary)</condition>
  <arm_group>
    <arm_group_label>Carbetocin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One ml of Carbitocin (100 mcg), was given as a bolus intravenous injection after labor of the baby at once.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Oxytocin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>One ml of Oxytocin (10 IU), was given as a bolus intravenous injection after labor of the baby at once.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carbetocin</intervention_name>
    <description>Heat stable Carbetocin, a clear colourless solution. Oxytocic activity: approximately 50 IU of oxytocin/vial. One ml of Carbitocin (100 mcg), was given as a bolus intravenous injection, slowly over 1 minute after labor of the baby at once. It was used once and no further doses were given.&#xD;
Drug was kept in cold storage (2 to 8°C).</description>
    <arm_group_label>Carbetocin</arm_group_label>
    <other_name>BABAL</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxytocin</intervention_name>
    <description>Oxytocin, a clear colourless solution. One ml of oxytocin (10 IU), was given as a bolus intravenous injection over 1 minute, after labor of the baby at once. Further doses can be given accordingly.&#xD;
Drug was kept in cold storage (2 to 8°C).</description>
    <arm_group_label>Oxytocin</arm_group_label>
    <other_name>Pitocin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients age ≥18 years&#xD;
&#xD;
          -  Singleton pregnancy&#xD;
&#xD;
          -  Full term gestation&#xD;
&#xD;
          -  Emergency cesarean section during labor&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cases of coagulopathy&#xD;
&#xD;
          -  Drug hypersensitivity&#xD;
&#xD;
          -  Medical diseases as; cardiac, hypertension, liver, renal or endocrine diseases&#xD;
&#xD;
          -  Uterine fibroids&#xD;
&#xD;
          -  Suspected placental pathology (accreta, previa or abruptio)&#xD;
&#xD;
          -  General anesthesia&#xD;
&#xD;
          -  Longitudinal uterine incision&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>43 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Taghreed K Alhaidari, CABOG</last_name>
    <role>Study Chair</role>
    <affiliation>Al Kindy College of Medicine, University of Baghdad</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Shayma S Al-Zubaidy, FICOG, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Al- Elweyia Maternity Teaching Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Alaa A Hussein, FICOG, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Al- Elweyia Maternity Teaching Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ulfat M Alnakkash, CABOG</last_name>
    <role>Principal Investigator</role>
    <affiliation>Al- Elweyia Maternity Teaching Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ahmed S Alnuaimi, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Baghdad College of Medicine/ University of Baghdad</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Al Kindy College of Medicine/ University of Baghdad</name>
      <address>
        <city>Baghdad</city>
        <zip>10096</zip>
        <country>Iraq</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Iraq</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 24, 2018</study_first_submitted>
  <study_first_submitted_qc>November 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <last_update_submitted>November 27, 2018</last_update_submitted>
  <last_update_submitted_qc>November 27, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 28, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Al-Kindy College of Medicine</investigator_affiliation>
    <investigator_full_name>Taghreed Alhaidari</investigator_full_name>
    <investigator_title>Assistant Professor / Consultant Obstetrician &amp; Gynecologist / Head of Scientific Affairs Unit</investigator_title>
  </responsible_party>
  <keyword>Oxytocin</keyword>
  <keyword>Carbetocin</keyword>
  <keyword>Emergency Caesarean Section</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Postpartum Hemorrhage</mesh_term>
    <mesh_term>Emergencies</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Oxytocin</mesh_term>
    <mesh_term>Carbetocin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant data that underlie the main outcomes' result reported in this article will be shared.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>Beginning 6 months and ending 24 months following article publication, unless otherwise stated by the publisher</ipd_time_frame>
    <ipd_access_criteria>The data will be available up to 24 months following article publication for anyone who wishes to access the data or for meta-analysis.</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03755531
org study id: 4 Al-KindyCM
nct id: NCT03755531
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Postpartum haemorrhage keeps to be the leading cause of maternal mortality in middle and
      low-income countries, including Iraq. Much advancement had been made in the field of
      treatment for postpartum haemorrhage but no much progress had been made in the field of
      prevention, where one of its main component is the administration of uterotonic, preferably
      oxytocin, immediately after birth of the baby.

      In many low- and middle income countries, the efficacy of oxytocin cannot be assured since
      access to sustained cold-chain is unavailable. Regarding the other uterotonics; ergometrine
      degrades when exposed to heat or light. Misoprostol degrades rapidly when exposed to
      Moisture.

      Innovation in the manufacture of carbetocin had meet the stability requirements for hot and
      humid climates.

      This study had been accomplished to evaluate the uterotonic effect of carbetocin compared
      with oxytocin for the prevention of postpartum haemorrhage in emergency caesarean delivery.
      Looking if carbetocin is superior to oxytocin in term of reduction in the need for additional
      uterotonic agents or the occurrence of PPH.
Setting and design:

      It is a double blinded randomized parallel clinical trial. That had been conducted at Al
      Elweyia Maternity Teaching Hospital in Baghdad during the period from Jan., 4th, 2018 to
      August, 1st, 2018. Written consent was insured for all the participants.

      Data collection:

      Three hundred and twenty pregnant women who were underwent emergency caesarean sections under
      regional anesthesia were enrolled in the study (due to limitation of carbetocin ampoules that
      were available). Those women were randomized to oxytocin or carbetocin in a rate of 2:1 (for
      prophylaxis of PPH in the active management of third stage of labour). Twenty cases were
      omitted since they were not fulfilled the eligibility criteria and only three hundred women
      were completed the study. They were divided into two groups:

      Group1 (case group): 100 pregnant women, whom they received carbetocin for the prevention of
      PPH.

      Group 2 (control group): 200 pregnant women, whom they received oxytocin for the prevention
      of PPH.

      Additional information including age, parity, past medical history, and body mass index (BMI)
      were taken.

      Intervention:

      The following steps were followed:

        1. Hemoglobin and hematocrit were assessed before caesarean section.

        2. One ml of either carbitocin (100 mcg) or oxytocin (10 IU) was given as a bolus
           intravenous injection by the anesthesiologist after labor of the baby at once.

        3. The placentae were delivered by controlled cord traction.

        4. It was the operating obstetrician decision to evaluated the uterine tone, bleeding
           intra-operatively and the need for an additional uterotonic and method of its
           administration, dose and duration.

        5. Our center usual regimen for uterine atony is an oxytocin (40 IU in 500 ml isotonic
           crystalloid solution) intravenous infusion over 4-5 hours.

      Follow up:

      For 24 hours was done, that is include:

        1. Evaluation of blood loss by the obstetrician and the anesthesiologist after skin
           closure, that is include the entire amount that had been suctioned, taken by the
           surgical gauzes or spilled in the surgical field, using visual estimation chart for
           assessment of blood loss.

        2. The need of any additional uterotonic drugs after the operation was recorded.

        3. The need of blood transfusion post delivery.

        4. The blood pressure and pulse rate of the women involved in the study were documented at
           0, 5, 10, 20, 30 and 60 minutes after the injection of the drug.

        5. The period of operation (skin cut into the final closure of the skin) was recorded.

        6. Intravenous fluid infusion was administered regularly and as it had been stated by the
           obstetricians and maintained after the operation until oral intake was started.

        7. Hemoglobin and hematocrit was assessed the day after the caesarean section.

      Statistical analysis:

      Statistical Package for Social Sciences (SPSS) version 21 was used. Descriptive statistics
      presented as (mean ± standard deviation) and frequencies as percentages. The database was
      examined for errors using range and logical data cleaning methods, and inconsistencies were
      remedied. Chi square test was used to compare between categorical variables (Fishers exact
      test used when expected variable was less than 20% of total) and t-test was used to compare
      between two means. Cohen's d, a standardized measure of effect size for difference between 2
      means, which can be compared across different variables and studies, since it has no unit of
      measurement was used. Significance level was set at P < 0.05.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: The anesthetist was the person in charge for giving the allocated drug after labor of the baby at once. Otherwise the operating obstetricians, the care givers, investigators and the ouctcomes assessor were all blinded to the type of the injection.
measure: Blood loss equal or more than 1000 ml
time frame: During the first 24 hours
description: Proportion of women with blood loss equal or more than 1000 ml in both study groups
measure: Use of additional uterotonics
time frame: During the first 24 hours
description: Proportion of the women whom they need additional uterotonic agents
measure: Blood pressure changes in carbetocin versus oxytocin group
time frame: Within one hour after administration of the drugs
description: Systolic and diastolic blood pressure changes that may occur in both groups
measure: Pulse rate changes in carbetocin versus oxytocin group
time frame: Within one hour after administration of the drugs
description: Detection of pulse rate changes that may occur in both groups
measure: Blood transfusion need
time frame: During the first 24 hours
description: Proportion of the women whom they need blood transfusion
arm group label: Carbetocin
arm group type: Experimental
description: One ml of Carbitocin (100 mcg), was given as a bolus intravenous injection after labor of the baby at once.
arm group label: Oxytocin
arm group type: Active Comparator
description: One ml of Oxytocin (10 IU), was given as a bolus intravenous injection after labor of the baby at once.
intervention type: Drug
intervention name: Carbetocin
description: Heat stable Carbetocin, a clear colourless solution. Oxytocic activity: approximately 50 IU of oxytocin/vial. One ml of Carbitocin (100 mcg), was given as a bolus intravenous injection, slowly over 1 minute after labor of the baby at once. It was used once and no further doses were given.
Drug was kept in cold storage (2 to 8°C).
arm group label: Carbetocin
other name: BABAL
intervention type: Drug
intervention name: Oxytocin
description: Oxytocin, a clear colourless solution. One ml of oxytocin (10 IU), was given as a bolus intravenous injection over 1 minute, after labor of the baby at once. Further doses can be given accordingly.
Drug was kept in cold storage (2 to 8°C).
arm group label: Oxytocin
other name: Pitocin
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 43 Years
healthy volunteers: No
last name: Taghreed K Alhaidari, CABOG
role: Study Chair
affiliation: Al Kindy College of Medicine, University of Baghdad
last name: Shayma S Al-Zubaidy, FICOG, MD
role: Principal Investigator
affiliation: Al- Elweyia Maternity Teaching Hospital
last name: Alaa A Hussein, FICOG, MD
role: Principal Investigator
affiliation: Al- Elweyia Maternity Teaching Hospital
last name: Ulfat M Alnakkash, CABOG
role: Principal Investigator
affiliation: Al- Elweyia Maternity Teaching Hospital
last name: Ahmed S Alnuaimi, PhD
role: Principal Investigator
affiliation: Baghdad College of Medicine/ University of Baghdad
facility: 
country: Iraq
responsible party type: Principal Investigator
investigator affiliation: Al-Kindy College of Medicine
investigator full name: Taghreed Alhaidari
investigator title: Assistant Professor / Consultant Obstetrician & Gynecologist / Head of Scientific Affairs Unit
mesh term: Postpartum Hemorrhage
mesh term: Emergencies
mesh term: Hemorrhage
mesh term: Oxytocin
mesh term: Carbetocin
sharing ipd: Yes
ipd description: Individual participant data that underlie the main outcomes' result reported in this article will be shared.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: Beginning 6 months and ending 24 months following article publication, unless otherwise stated by the publisher
ipd access criteria: The data will be available up to 24 months following article publication for anyone who wishes to access the data or for meta-analysis.