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Carbetocin vs. Oxytocin at Elective Cesarean Section

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ClinicalTrials.gov Identifier: NCT03168698
Recruitment Status : Recruiting
First Posted : May 30, 2017
Last Update Posted : September 14, 2018
Sponsor:
Information provided by (Responsible Party):
Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Brief Summary:
The study investigators are comparing 2 drugs (oxytocin and carbetocin) at 2 different dosages, to help prevent serious bleeding (hemorrhage) after cesarean deliveries. These drugs are used routinely to help contract the uterus and keep it contracted after the delivery of the baby and placenta; this reduces the amount of blood you might lose. At Mount Sinai Hospital, currently oxytocin is used, but its effect on the uterus is much shorter than that of carbetocin. Internationally, there is no consensus as to what the most effective drug to use is and at which dose. The Society of Obstetricians and Gynaecologists of Canada has recently revised its guidelines to suggest 100 micrograms (mcg) of carbetocin as the drug of choice at elective cesarean section. Guidelines from the United Kingdom and the United States currently suggest oxytocin at various doses as the drug of choice at elective cesarean sections. Previous studies at Mount Sinai Hospital have shown that lower doses of oxytocin, 0.35 International Units (IU), and carbetocin, 20 mcg, may be as effective as the higher recommended doses. The investigators plan to conduct a large study to confirm these findings so that they can use the most appropriate dose in the future. Furthermore, the investigators hope to demonstrate that side effects are lower with the lower dose regimens.

Condition or disease Intervention/treatment Phase
Postpartum Hemorrhage Drug: Carbetocin Drug: Oxytocin Not Applicable

Detailed Description:

Postpartum hemorrhage (PPH) is a major cause of maternal death worldwide. Oxytocin is the most commonly used uterotonic drug to prevent and treat PPH in the world. However, oxytocin has a very short duration of action, requiring a continuous infusion to achieve sustained uterotonic activity. Moreover, large doses are associated with adverse effects like hypotension, nausea, vomiting, dysrhythmias and ST changes. The Society of Obstetricians and Gynecologists of Canada (SOGC) has recommended a single dose of 100 mcg of the longer acting carbetocin at elective cesarean section to promote uterine contraction. In multiple studies performed at Mount Sinai Hospital, we have shown that smaller doses of oxytocin (ED 90 0.35 IU) and carbetocin (ED 90 14.8 mcg) are effective in achieving adequate uterine tone at elective cesarean section. No study has directly compared the high dose regimens with the low dose regimens; therefore a large double-blind randomized controlled trial is necessary to show the non-inferiority of the lower doses of both drugs.

There is a lack of consensus as to what the optimal uterotonic regime is globally. Furthermore, variability in the international guidelines regarding the choice of first line uterotonic in prevention of PPH adds to the confusion. With the widespread availability of carbetocin in some of the developed countries, including Canada, the question of which uterotonic to adopt and at which dose becomes even more difficult to ascertain. Studies that have currently been published suggest the ED90 doses of carbetocin and oxytocin provide adequate uterine contraction with possibly fewer side effects associated with the lower dosed regimens. These advantages may provide a better safety profile and patient satisfaction. To the best of our knowledge, no studies have compared the low doses (ED90) of oxytocin vs. carbetocin, or low (ED90) vs high (conventional) doses of the two drugs in the setting of elective cesarean section. The results of this study will provide evidence on the efficacy and safety of the ED90 dosing compared directly to the higher dosing of both drugs.

Our hypothesis is that the ED90 doses of carbetocin and oxytocin will not be inferior to the higher dosing as determined by the intensity of uterine contraction using a VNRS in women undergoing elective cesarean section. We anticipate that the intensity of uterine contraction using the VNRS at 2 minutes post administration of all drugs will fall within the predetermined margin to signify non-inferiority of all regimens.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Carbetocin vs. Oxytocin at Elective Cesarean Section: a Double-blind, Randomized Controlled Non-inferiority Trial of High and Low Dose Regimens
Actual Study Start Date : May 25, 2017
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Oxytocin

Arm Intervention/treatment
Active Comparator: Carbetocin 20mcg
Carbetocin 20mcg, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
Drug: Carbetocin
Patient is given carbetocin (20 or 100 mcg) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
Other Name: Duratocin

Active Comparator: Carbetocin 100mcg
Carbetocin 100mcg, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
Drug: Carbetocin
Patient is given carbetocin (20 or 100 mcg) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
Other Name: Duratocin

Active Comparator: Oxytocin 0.5IU
Oxytocin 0.5IU, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
Drug: Oxytocin
Patient is given oxytocin (0.5 or 5 IU) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
Other Name: Pitocin

Active Comparator: Oxytocin 5IU
Oxytocin 5IU, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
Drug: Oxytocin
Patient is given oxytocin (0.5 or 5 IU) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
Other Name: Pitocin




Primary Outcome Measures :
  1. Uterine Tone 2 minutes [ Time Frame: 2 minutes ]
    Intensity of uterine tone on a VNRS scale of 0-10 as evaluated by the obstetrician at 2 minutes after completion of injection of the bolus study drug.


Secondary Outcome Measures :
  1. Uterine Tone 5 minutes [ Time Frame: 5 minutes ]
    Intensity of uterine tone on a VNRS scale of 0-10 as evaluated by the obstetrician at 5 minutes after completion of injection of the bolus study drug.

  2. Uterine Tone 10 minutes [ Time Frame: 10 minutes ]
    Intensity of uterine tone on a VNRS scale of 0-10 as evaluated by the obstetrician at 10 minutes after completion of injection of the bolus study drug.

  3. Additional uterotonics - operating room [ Time Frame: 1 hour ]
    The use of additional uterotonic agents in the operating room

  4. Additional uterotonics - 24 hours [ Time Frame: 24 hours ]
    The use of additional uterotonic agents at any time after admission to the recovery room and up to 24 hours post delivery

  5. Estimated blood loss [ Time Frame: 24 hours ]
    Blood loss will be calculated through the difference in hematocrit values assessed prior to and at the end of 24 hours after the cesarean section.

  6. Hypotension: systolic blood pressure less than 80% of baseline [ Time Frame: 2 hours ]
    Systolic blood pressure < 80% of baseline, from drug administration until end of surgery

  7. Hypertension: systolic blood pressure greater than 120% of baseline [ Time Frame: 2 hours ]
    Systolic blood pressure > 120% of baseline, from drug administration until end of surgery

  8. Tachycardia: heart rate greater than 130% of baseline [ Time Frame: 2 hours ]
    Heart rate > 130% of baseline, from drug administration until end of surgery

  9. Bradycardia: heart rate less than 70% of baseline [ Time Frame: 2 hours ]
    Heart rate < 70% of baseline, from drug administration until end of surgery

  10. Presence of ventricular tachycardia: ECG [ Time Frame: 2 hours ]
    Presence of ventricular tachycardia as recorded by ECG, from drug administration until end of surgery

  11. Presence of atrial fibrillation: ECG [ Time Frame: 2 hours ]
    Presence of atrial fibrillation as recorded by ECG, from drug administration until end of surgery

  12. Presence of atrial flutter: ECG [ Time Frame: 2 hours ]
    Presence of atrial flutter as recorded by ECG, from drug administration until end of surgery

  13. Presence of nausea: questionnaire [ Time Frame: 2 hours ]
    The presence of nausea and number of episodes, from drug administration until end of surgery, as reported by the patient

  14. Presence of vomiting: questionnaire [ Time Frame: 2 hours ]
    The presence of vomiting and number of episodes, from drug administration until end of surgery

  15. Presence of chest pain: questionnaire [ Time Frame: 2 hours ]
    Any presence of chest pain, from drug administration until end of surgery, as reported by the patient

  16. Presence of shortness of breath: questionnaire [ Time Frame: 2 hours ]
    Any presence of shortness of breath, from drug administration until end of surgery, as reported by the patient

  17. Presence of headache: questionnaire [ Time Frame: 2 hours ]
    Any presence of headache, from drug administration until end of surgery, as reported by the patient

  18. Presence of flushing: questionnaire [ Time Frame: 2 hours ]
    Any presence of flushing, from drug administration until end of surgery



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Elective cesarean section under spinal anesthesia.
  • Written informed consent to participate in this study.
  • Full-term pregnancy
  • Non labouring patients

Exclusion Criteria:

  • Refusal to give written informed consent.
  • Allergy or hypersensitivity to carbetocin or oxytocin.
  • Labouring patients
  • Need for general anesthesia
  • Conditions that predispose to uterine atony and postpartum hemorrhage such as placenta previa, multiple gestation, preeclampsia, eclampsia, macrosomia, polyhydramnios, uterine fibroids, previous history of uterine atony and postpartum bleeding, or bleeding diathesis.
  • Hepatic, renal, and cardiovascular disease.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03168698


Contacts
Contact: Mrinalini Balki, MD 416-586-4800 ext 5270 mrinalini.balki@uhn.ca

Locations
Canada, Ontario
Mount Sinai Hospital Recruiting
Toronto, Ontario, Canada, M5G1X5
Contact: Mrinalini Balki, MD    416-586-4800 ext 5270    mrinalini.balki@uhn.ca   
Sub-Investigator: Jose CA Carvalho, MD         
Sub-Investigator: Abdulla Sadiq, MD         
Sub-Investigator: Farine Dan, MD         
Sub-Investigator: Downey Kristi, MSc         
Sub-Investigator: Xiang Ye, MSc         
Sponsors and Collaborators
Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Investigators
Principal Investigator: Mrinalini Balki, MD MOUNT SINAI HOSPITAL

Responsible Party: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
ClinicalTrials.gov Identifier: NCT03168698     History of Changes
Other Study ID Numbers: 17-01
First Posted: May 30, 2017    Key Record Dates
Last Update Posted: September 14, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Samuel Lunenfeld Research Institute, Mount Sinai Hospital:
pregnancy
postpartum hemorrhage
cesarean delivery
carbetocin
duratocin
oxytocin

Additional relevant MeSH terms:
Hemorrhage
Postpartum Hemorrhage
Pathologic Processes
Obstetric Labor Complications
Pregnancy Complications
Puerperal Disorders
Uterine Hemorrhage
Oxytocin
Carbetocin
Oxytocics
Reproductive Control Agents
Physiological Effects of Drugs