Postpartum HemorrhageNCT03168698
Carbetocin vs. Oxytocin at Elective Cesarean Section
A study testing Carbetocin and Oxytocin in people with Postpartum Hemorrhage, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 2 sites in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Postpartum Hemorrhage
- What is being tested?
- Carbetocin and Oxytocin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 278 participants
- Where
- 2 sitesCanada
- Study dates
- 25 May 2017to 18 Dec 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Elective cesarean section under spinal anesthesia.
- Written informed consent to participate in this study.
- Full-term pregnancy
- Non labouring patients
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
McMaster University Medical Centre (MUMC)
Hamilton, Ontario, L8N 3Z5
Mount Sinai Hospital
Toronto, Ontario, M5G1X5
About this study
Official title: Carbetocin vs. Oxytocin at Elective Cesarean Section: a Double-blind, Randomized Controlled Non-inferiority Trial of High and Low Dose Regimens
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.
Read the 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.
- Conditions
- Postpartum Hemorrhage
- Being tested
- Carbetocin, Oxytocin
- Keywords
- pregnancy, postpartum hemorrhage, cesarean delivery, carbetocin, duratocin, oxytocin
- Medical subject headings
- Postpartum Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarbetocinDrug
Also called Duratocin
Patient is given carbetocin (20 or 100 mcg) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
OxytocinDrug
Also called Pitocin
Patient is given oxytocin (0.5 or 5 IU) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.
| Study group | Role | What they receive |
|---|---|---|
| Carbetocin 20mcg | Active comparator | Carbetocin 20mcg, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby. Receives: Drug: Carbetocin |
| Carbetocin 100mcg | Active comparator | Carbetocin 100mcg, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby. Receives: Drug: Carbetocin |
| Oxytocin 0.5IU | Active comparator | Oxytocin 0.5IU, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby. Receives: Drug: Oxytocin |
| Oxytocin 5IU | Active comparator | Oxytocin 5IU, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby. Receives: Drug: Oxytocin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Uterine Tone 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.
Measured: 2 minutes
Secondary outcomes (18)
Uterine Tone 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.
Measured: 5 minutes
Uterine Tone 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.
Measured: 10 minutes
Additional uterotonics - operating room
The use of additional uterotonic agents in the operating room
Measured: 1 hour
Additional uterotonics - 24 hours
The use of additional uterotonic agents at any time after admission to the recovery room and up to 24 hours post delivery
Measured: 24 hours
Estimated blood loss
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.
Measured: 24 hours
Hypotension: systolic blood pressure less than 80% of baseline
Systolic blood pressure < 80% of baseline, from drug administration until end of surgery
Measured: 2 hours
Hypertension: systolic blood pressure greater than 120% of baseline
Systolic blood pressure > 120% of baseline, from drug administration until end of surgery
Measured: 2 hours
Tachycardia: heart rate greater than 130% of baseline
Heart rate > 130% of baseline, from drug administration until end of surgery
Measured: 2 hours
Bradycardia: heart rate less than 70% of baseline
Heart rate < 70% of baseline, from drug administration until end of surgery
Measured: 2 hours
Presence of ventricular tachycardia: ECG
Presence of ventricular tachycardia as recorded by ECG, from drug administration until end of surgery
Measured: 2 hours
Presence of atrial fibrillation: ECG
Presence of atrial fibrillation as recorded by ECG, from drug administration until end of surgery
Measured: 2 hours
Presence of atrial flutter: ECG
Presence of atrial flutter as recorded by ECG, from drug administration until end of surgery
Measured: 2 hours
Presence of nausea: questionnaire
The presence of nausea and number of episodes, from drug administration until end of surgery, as reported by the patient
Measured: 2 hours
Presence of vomiting: questionnaire
The presence of vomiting and number of episodes, from drug administration until end of surgery
Measured: 2 hours
Presence of chest pain: questionnaire
Any presence of chest pain, from drug administration until end of surgery, as reported by the patient
Measured: 2 hours
Presence of shortness of breath: questionnaire
Any presence of shortness of breath, from drug administration until end of surgery, as reported by the patient
Measured: 2 hours
Presence of headache: questionnaire
Any presence of headache, from drug administration until end of surgery, as reported by the patient
Measured: 2 hours
Presence of flushing: questionnaire
Any presence of flushing, from drug administration until end of surgery
Measured: 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2017
- Study start25 May 2017
- Primary completion17 Dec 2020
- Study completion18 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postpartum HemorrhageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 278 participants (actual)
Sponsor and investigators
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mrinalini Balki, MD, Principal investigator, MOUNT SINAI HOSPITAL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03168698
- Sponsor's protocol ID
- 17-01
- Status last verified
- Feb 2021
- First submitted
- 23 May 2017
- Last updated
- 3 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Carbetocin vs. Oxytocin at Elective Cesarean Section: a Double-blind, Randomized Controlled Non-inferiority Trial of High and Low Dose Regimens
- ClinicalTrials.gov ID
- NCT03168698
- Acronym / sponsor ID
- 17-01
- Conditions
- Postpartum Hemorrhage
- Keywords
- pregnancy, postpartum hemorrhage, cesarean delivery, carbetocin, duratocin, oxytocin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 278 participants (actual)
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai HospitalUniversity, hospital or other
- Study start
- 25 May 2017 (actual)
- Primary completion
- 17 Dec 2020 (actual)
- Study completion
- 18 Dec 2020 (actual)
- First posted
- 30 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Carbetocin 20mcg | Active comparator | Drug: CarbetocinCarbetocin 20mcg, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby. |
| Carbetocin 100mcg | Active comparator | Drug: CarbetocinCarbetocin 100mcg, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby. |
| Oxytocin 0.5IU | Active comparator | Drug: OxytocinOxytocin 0.5IU, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby. |
| Oxytocin 5IU | Active comparator | Drug: OxytocinOxytocin 5IU, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Elective cesarean section under spinal anesthesia.
- Written informed consent to participate in this study.
- Full-term pregnancy
- Non labouring patients
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarbetocinAlso: DuratocinPatient is given carbetocin (20 or 100 mcg) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby. | Drug | Carbetocin 100mcg, Carbetocin 20mcg |
| OxytocinAlso: PitocinPatient is given oxytocin (0.5 or 5 IU) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby. | Drug | Oxytocin 0.5IU, Oxytocin 5IU |
Primary outcome
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.
18 secondary outcomes
Uterine Tone 5 minutes
Time frame: 5 minutes
Uterine Tone 10 minutes
Time frame: 10 minutes
Additional uterotonics - operating room
Time frame: 1 hour
Additional uterotonics - 24 hours
Time frame: 24 hours
Estimated blood loss
Time frame: 24 hours
Hypotension: systolic blood pressure less than 80% of baseline
Time frame: 2 hours
Hypertension: systolic blood pressure greater than 120% of baseline
Time frame: 2 hours
Tachycardia: heart rate greater than 130% of baseline
Time frame: 2 hours
Bradycardia: heart rate less than 70% of baseline
Time frame: 2 hours
Presence of ventricular tachycardia: ECG
Time frame: 2 hours
Presence of atrial fibrillation: ECG
Time frame: 2 hours
Presence of atrial flutter: ECG
Time frame: 2 hours
Presence of nausea: questionnaire
Time frame: 2 hours
Presence of vomiting: questionnaire
Time frame: 2 hours
Presence of chest pain: questionnaire
Time frame: 2 hours
Presence of shortness of breath: questionnaire
Time frame: 2 hours
Presence of headache: questionnaire
Time frame: 2 hours
Presence of flushing: questionnaire
Time frame: 2 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mrinalini Balki, MD principal investigator
MOUNT SINAI HOSPITAL
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Carbetocin and Oxytocin in people with Postpartum Hemorrhage, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Uterine Tone 2 minutes (time frame: 2 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2021.