<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/NCT01725243</url>
  </required_header>
  <id_info>
    <org_study_id>12-07</org_study_id>
    <nct_id>NCT01725243</nct_id>
  </id_info>
  <brief_title>Carbetocin at Cesarean Delivery for Labor Arrest</brief_title>
  <official_title>Carbetocin at Cesarean Delivery for Labor Arrest: A Dose Finding Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Samuel Lunenfeld Research Institute, Mount Sinai Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Samuel Lunenfeld Research Institute, Mount Sinai Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In 2009, the Society of Obstetricians and Gynecologists Canada, which produces national&#xD;
      clinical guidelines on important women's health issues, recommended that a bolus of&#xD;
      carbetocin 100 mcg into your vein should be used at elective cesarean delivery instead of&#xD;
      oxytocin infusion for the prevention of bleeding after you deliver your baby. Similar to&#xD;
      oxytocin, carbetocin has side effects that are dose-related. Although 100 mcg has been the&#xD;
      recommend dose, studies in nonlaboring women suggest that doses lower than 100 mcg may be&#xD;
      used to achieve the same degree of uterine contractility with less side effects. So far, the&#xD;
      ideal dose to be used in cesarean sections for labouring women who have failure to progress&#xD;
      in labour (failure of your cervix to dilate adequately to 10cm or the baby's head not&#xD;
      descending the birth canal) has not been determined. This study is designed to determine the&#xD;
      minimum carbetocin dose required during cesarean delivery for 'failure to progress' to&#xD;
      achieve the best effect.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Post-partum hemorrhage (PPH) is a major cause of maternal death worldwide. Oxytocin is the&#xD;
      most common uterotonic drug used to prevent and treat PPH in North America, however, there&#xD;
      are some limitations to its use. Oxytocin has a very short duration of action, which requires&#xD;
      a continuous infusion to achieve sustained uterotonic activity. The Society of Obstetricians&#xD;
      and Gynecologists of Canada (SOGC) has recently recommended a single 100mcg dose of&#xD;
      carbetocin at elective Cesarean delivery to promote uterine contraction and prevent post&#xD;
      partum hemorrhage (PPH), in lieu of the more traditional oxytocin regimens. Carbetocin lasts&#xD;
      4 to 7 times longer than oxytocin, with a similar side effect profile and apparent greater&#xD;
      efficacy rate.&#xD;
&#xD;
      The evidence reported for Carbetocin use in the literature has mostly been based upon low&#xD;
      risk non-laboring patients undergoing elective cesarean deliveries. At present, only 2&#xD;
      studies have looked at the use of Carbetocin in low risk patients requiring emergency&#xD;
      cesarean deliveries. The minimum effective dose (ED90) of carbetocin in laboring women has&#xD;
      not been determined so far. Similar to oxytocin, the ED90 of Carbetocin is likely to be&#xD;
      higher in laboring women undergoing Cesarean deliveries as compared to the non-laboring&#xD;
      women, due to the effect of the desensitization phenomenon.&#xD;
&#xD;
      This study will be conducted as a prospective, randomized, up-down sequential allocation&#xD;
      trial. The success or fail of a patient in the study will determine the dose given to future&#xD;
      patients. Dosage will be increased for patients following a failed case, and kept the same&#xD;
      for patients following successful cases. Following a successful case, there is also a 1 in 9&#xD;
      chance that the dose will be decreased for the next patient.&#xD;
&#xD;
      The results of this study will establish the minimum effective dose of carbetocin for uterine&#xD;
      contraction at cesarean delivery for labor arrest. This will likely minimize unnecessary side&#xD;
      effects caused by a large bolus dose of the drug, and improve quality and safety of patient&#xD;
      care.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">April 2013</completion_date>
  <primary_completion_date type="Actual">March 2013</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>need for additional uterotonics</measure>
    <time_frame>30 minutes</time_frame>
    <description>need for additional uterotonics in the OR at the time of cesarean section based upon the assessment of unsatisfactory/indeterminate uterine tone in response to the single bolus of carbetocin.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>uterine tone</measure>
    <time_frame>10 minutes</time_frame>
    <description>Incidence of satisfactory, unsatisfactory and indeterminate uterine tone at every minute for five minutes and at 10 minutes following the completion of the injection of carbetocin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>uterine tone</measure>
    <time_frame>2 hours</time_frame>
    <description>Incidence of satisfactory, unsatisfactory/ indeterminate uterine tone as determined by the obstetrician/nurse after trans-abdominal palpation of the uterus in PACU within 2 hours of delivery of the placenta</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>need for additional uterotonic</measure>
    <time_frame>24 hours</time_frame>
    <description>Need for delayed additional uterotonics within 24 hours after delivery outside the OR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood loss</measure>
    <time_frame>24 hours</time_frame>
    <description>Estimated blood loss will be calculated using blood results prior to the cesarean delivery and 24 hours post-delivery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>side effects</measure>
    <time_frame>2 hours</time_frame>
    <description>Any of the following will be noted up to 2 hours post delivery: systolic blood pressure &lt; 80% of pre-delivery values, tachycardia &gt; 30% pre-delivery levels, bradycardia &lt; 30% pre-delivery levels, other dysrhythmias, nausea, vomiting, chest pain, shortness of breath, headache, flushing, others</description>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Postpartum Hemorrhage</condition>
  <arm_group>
    <arm_group_label>Carbetocin 10mcg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Carbetocin 10mcg IV, once following delivery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Carbetocin 20mcg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Carbetocin 20mcg IV, once following delivery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Carbetocin 40mcg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Carbetocin 40mcg IV, once following delivery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Carbetocin 60mcg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Carbetocin 60mcg IV, once following delivery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Carbetocin 80mcg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Carbetocin 80mcg IV, once following delivery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Carbetocin 100mcg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Carbetocin 100mcg IV, once following delivery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Carbetocin 120mcg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Carbetocin 120mcg IV, once following delivery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Carbetocin 140mcg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Carbetocin 140mcg IV, once following delivery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carbetocin</intervention_name>
    <description>Carbetocin IV, over 1 minute following delivery. Doses: 10, 20, 40, 60, 80, 100, 120 or 140mcg</description>
    <arm_group_label>Carbetocin 100mcg</arm_group_label>
    <arm_group_label>Carbetocin 10mcg</arm_group_label>
    <arm_group_label>Carbetocin 120mcg</arm_group_label>
    <arm_group_label>Carbetocin 140mcg</arm_group_label>
    <arm_group_label>Carbetocin 20mcg</arm_group_label>
    <arm_group_label>Carbetocin 40mcg</arm_group_label>
    <arm_group_label>Carbetocin 60mcg</arm_group_label>
    <arm_group_label>Carbetocin 80mcg</arm_group_label>
    <other_name>Duratocin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients who have given written informed consent to participate in this study.&#xD;
&#xD;
          -  All patients planned for uncomplicated low transverse cesarean delivery secondary to&#xD;
             labor arrest, under epidural anesthesia.&#xD;
&#xD;
          -  ≥37 week pregnancy&#xD;
&#xD;
          -  Singleton pregnancy&#xD;
&#xD;
          -  Patients who have received oxytocin for at least 4 hours for labor augmentation&#xD;
&#xD;
          -  ASA 1 or 2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refusal or inability to obtain informed consent.&#xD;
&#xD;
          -  All patients who claim allergy or hypersensitivity to oxytocin and carbetocin.&#xD;
&#xD;
          -  Previous history of uterine atony or PPH&#xD;
&#xD;
          -  Risk factors for PPH such as pre-eclampsia, polyhydramnios, uterine fibroids, bleeding&#xD;
             diathesis and chorioamnionitis etc.&#xD;
&#xD;
          -  Abnormal placental implantation (known or suspected)&#xD;
&#xD;
          -  &gt; 3 cesarean sections in the past&#xD;
&#xD;
          -  Previous classic uterine incision&#xD;
&#xD;
          -  Macrosomia - Estimated fetal weight &gt; 4500g&#xD;
&#xD;
          -  Hemoglobin &lt; 100g/L&#xD;
&#xD;
          -  Cesarean section under general anesthesia&#xD;
&#xD;
          -  ASA 3 and 4 or patients with hepatic, renal, cardiac (eg. Coronary artery disease) and&#xD;
             vascular disease&#xD;
&#xD;
          -  Genital development problems (eg. Abnormal uterus, cervix, vagina, etc.)&#xD;
&#xD;
          -  Uncontrolled hypotension or hypertension&#xD;
&#xD;
          -  Uncontrolled diabetes&#xD;
&#xD;
          -  Abnormal heart rhythms and bradycardia&#xD;
&#xD;
          -  Drug abusers&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mrinalini Balki, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>MOUNT SINAI HOSPITAL</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G1X5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2013</verification_date>
  <study_first_submitted>November 8, 2012</study_first_submitted>
  <study_first_submitted_qc>November 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 12, 2012</study_first_posted>
  <last_update_submitted>May 28, 2013</last_update_submitted>
  <last_update_submitted_qc>May 28, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 30, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>pregnancy</keyword>
  <keyword>postpartum hemorrhage</keyword>
  <keyword>Cesarean delivery</keyword>
  <keyword>carbetocin</keyword>
  <keyword>failure to progress in labor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Postpartum Hemorrhage</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carbetocin</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01725243
org study id: 12-07
nct id: NCT01725243
lead sponsor: 
has dmc: No
In 2009, the Society of Obstetricians and Gynecologists Canada, which produces national
      clinical guidelines on important women's health issues, recommended that a bolus of
      carbetocin 100 mcg into your vein should be used at elective cesarean delivery instead of
      oxytocin infusion for the prevention of bleeding after you deliver your baby. Similar to
      oxytocin, carbetocin has side effects that are dose-related. Although 100 mcg has been the
      recommend dose, studies in nonlaboring women suggest that doses lower than 100 mcg may be
      used to achieve the same degree of uterine contractility with less side effects. So far, the
      ideal dose to be used in cesarean sections for labouring women who have failure to progress
      in labour (failure of your cervix to dilate adequately to 10cm or the baby's head not
      descending the birth canal) has not been determined. This study is designed to determine the
      minimum carbetocin dose required during cesarean delivery for 'failure to progress' to
      achieve the best effect.
Post-partum hemorrhage (PPH) is a major cause of maternal death worldwide. Oxytocin is the
      most common uterotonic drug used to prevent and treat PPH in North America, however, there
      are some limitations to its use. Oxytocin has a very short duration of action, which requires
      a continuous infusion to achieve sustained uterotonic activity. The Society of Obstetricians
      and Gynecologists of Canada (SOGC) has recently recommended a single 100mcg dose of
      carbetocin at elective Cesarean delivery to promote uterine contraction and prevent post
      partum hemorrhage (PPH), in lieu of the more traditional oxytocin regimens. Carbetocin lasts
      4 to 7 times longer than oxytocin, with a similar side effect profile and apparent greater
      efficacy rate.

      The evidence reported for Carbetocin use in the literature has mostly been based upon low
      risk non-laboring patients undergoing elective cesarean deliveries. At present, only 2
      studies have looked at the use of Carbetocin in low risk patients requiring emergency
      cesarean deliveries. The minimum effective dose (ED90) of carbetocin in laboring women has
      not been determined so far. Similar to oxytocin, the ED90 of Carbetocin is likely to be
      higher in laboring women undergoing Cesarean deliveries as compared to the non-laboring
      women, due to the effect of the desensitization phenomenon.

      This study will be conducted as a prospective, randomized, up-down sequential allocation
      trial. The success or fail of a patient in the study will determine the dose given to future
      patients. Dosage will be increased for patients following a failed case, and kept the same
      for patients following successful cases. Following a successful case, there is also a 1 in 9
      chance that the dose will be decreased for the next patient.

      The results of this study will establish the minimum effective dose of carbetocin for uterine
      contraction at cesarean delivery for labor arrest. This will likely minimize unnecessary side
      effects caused by a large bolus dose of the drug, and improve quality and safety of patient
      care.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: need for additional uterotonics
time frame: 30 minutes
description: need for additional uterotonics in the OR at the time of cesarean section based upon the assessment of unsatisfactory/indeterminate uterine tone in response to the single bolus of carbetocin.
measure: uterine tone
time frame: 10 minutes
description: Incidence of satisfactory, unsatisfactory and indeterminate uterine tone at every minute for five minutes and at 10 minutes following the completion of the injection of carbetocin.
measure: uterine tone
time frame: 2 hours
description: Incidence of satisfactory, unsatisfactory/ indeterminate uterine tone as determined by the obstetrician/nurse after trans-abdominal palpation of the uterus in PACU within 2 hours of delivery of the placenta
measure: need for additional uterotonic
time frame: 24 hours
description: Need for delayed additional uterotonics within 24 hours after delivery outside the OR.
measure: Blood loss
time frame: 24 hours
description: Estimated blood loss will be calculated using blood results prior to the cesarean delivery and 24 hours post-delivery.
measure: side effects
time frame: 2 hours
description: Any of the following will be noted up to 2 hours post delivery: systolic blood pressure < 80% of pre-delivery values, tachycardia > 30% pre-delivery levels, bradycardia < 30% pre-delivery levels, other dysrhythmias, nausea, vomiting, chest pain, shortness of breath, headache, flushing, others
arm group label: Carbetocin 10mcg
arm group type: Active Comparator
description: Carbetocin 10mcg IV, once following delivery.
arm group label: Carbetocin 20mcg
arm group type: Active Comparator
description: Carbetocin 20mcg IV, once following delivery.
arm group label: Carbetocin 40mcg
arm group type: Active Comparator
description: Carbetocin 40mcg IV, once following delivery.
arm group label: Carbetocin 60mcg
arm group type: Active Comparator
description: Carbetocin 60mcg IV, once following delivery.
arm group label: Carbetocin 80mcg
arm group type: Active Comparator
description: Carbetocin 80mcg IV, once following delivery.
arm group label: Carbetocin 100mcg
arm group type: Active Comparator
description: Carbetocin 100mcg IV, once following delivery.
arm group label: Carbetocin 120mcg
arm group type: Active Comparator
description: Carbetocin 120mcg IV, once following delivery.
arm group label: Carbetocin 140mcg
arm group type: Active Comparator
description: Carbetocin 140mcg IV, once following delivery.
intervention type: Drug
intervention name: Carbetocin
description: Carbetocin IV, over 1 minute following delivery. Doses: 10, 20, 40, 60, 80, 100, 120 or 140mcg
arm group label: Carbetocin 100mcg
arm group label: Carbetocin 10mcg
arm group label: Carbetocin 120mcg
arm group label: Carbetocin 140mcg
arm group label: Carbetocin 20mcg
arm group label: Carbetocin 40mcg
arm group label: Carbetocin 60mcg
arm group label: Carbetocin 80mcg
other name: Duratocin
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mrinalini Balki, MD
role: Principal Investigator
affiliation: MOUNT SINAI HOSPITAL
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Postpartum Hemorrhage
mesh term: Hemorrhage
mesh term: Carbetocin