Postpartum HemorrhageNCT03672045
Carbetocin at Elective Cesarean Deliveries: A Dose-finding Study in Women With BMI ≥ 40kg/m2
A study testing Carbetocin in people with Postpartum Hemorrhage, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 1 site in Canada.
Trial summary
Postpartum hemorrhage (PPH) due to uterine atony is a major cause of maternal morbidity and mortality. Carbetocin is a uterotonic with a superior pharmacokinetic profile to oxytocin. 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
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteCanada
- Study dates
- 19 Nov 2018to 17 May 2019
- 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
- BMI ≥40kg/m2
- Elective cesarean delivery under regional anesthesia
- Gestational age ≥ 37 weeks
- No known additional risk factors for postpartum hemorrhage
- Written informed consent to participate in this study
Who cannot join
- Refusal to give written informed consent
- Allergy or hypersensitivity to carbetocin or oxytocin
- Conditions (other than high BMI) that may predispose to uterine atony and postpartum hemorrhage such as placenta previa, multiple gestation, polyhydramnios, uterine fibroids, previous history of uterine atony and postpartum bleeding, or bleeding diathesis.
- Hepatic, renal, and vascular disease
- Use of general anesthesia prior to the administration of the study drug
Trial locations and contacts
1 site in 1 country.
About this study
Postpartum hemorrhage (PPH) due to uterine atony is a major cause of maternal morbidity and mortality. Carbetocin is a uterotonic with a superior pharmacokinetic profile to oxytocin. In a study performed at Mount Sinai Hospital, the investigators have shown that smaller doses of carbetocin (14.8 mcg) are as effective in achieving adequate uterine tone at elective cesarean section compared to the current recommended dose of 100mcg. However, this study was limited to those women with a body mass index (BMI) of <40 kg/m2. Maternal obesity has been shown to increase the risks of hemorrhage secondary to uterine atony, therefore the investigators wish to perform a dose finding study to determine the ED90 of carbetocin at caesarean section in those women with a BMI>40.
Read the detailed description
Postpartum hemorrhage (PPH) is one of the leading causes of death during childbirth and accounts for an estimated 140,000 deaths per year worldwide. The World Health Organization (WHO) recommends active management of the third stage of labor to prevent PPH, even in low risk patients. Prophylactic uterotonic drugs administered after delivery are the main element of active management of the third stage and have been demonstrated to reduce the incidence of PPH by up to 40%.
Oxytocin is the most commonly used uterotonic in North America, however it has a very short duration of action and requires a continuous infusion to achieve sustained effect, with large doses associated with adverse effects like low blood pressure, nausea, vomiting, abnormal heart rhythms and changes on ECG. Carbetocin is a synthetic oxytocin analogue. It causes uterine contraction via the same mechanism as oxytocin. Its duration of action is 4 to 7 times that of oxytocin due to an increased biological half-life in plasma and at the oxytocin receptors in the uterus. The Society of Obstetricians and Gynecologists of Canada (SOGC) has recommended a single dose of 100 mcg of carbetocin at elective cesarean delivery to promote uterine contraction. In a study performed at Mount Sinai Hospital, the investigators have shown that smaller doses of carbetocin (14.8 mcg) are effective in achieving adequate uterine tone at elective cesarean section. However this study was limited to those women with a BMI of <40 kg/m2
The prevalence of obesity is increasing in young women and some studies have shown that obese women have higher rates of caesarean delivery compared to non-obese women. Other studies have demonstrated an increased risk of hemorrhage due to poor uterine tone in obese women. Laboratory studies show that BMI alone appears to contribute to blunted uterine muscle responses and therefore contraction responses to oxytocin in obese women. Previous dose finding studies have excluded those women with a BMI of ≥40kgm2. Therefore, the investigators wish to perform a double-blind dose finding study using the biased coin up-and-down sequential allocation technique to determine the ED90 of carbetocin at caesarean section in those women with a BMI>40.
- Conditions
- Postpartum Hemorrhage
- Being tested
- Carbetocin
- Keywords
- pregnancy, postpartum hemorrhage, Cesarean delivery, carbetocin
- 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
carbetocin administered IV, over 1 minute following delivery of the fetal head
| Study group | Role | What they receive |
|---|---|---|
| Carbetocin 10mcg | Active comparator | Patient is given 10 mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head. Receives: Drug: Carbetocin |
| Carbetocin 20mcg | Active comparator | Patient is given 20 mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head. Receives: Drug: Carbetocin |
| Carbetocin 40mcg | Active comparator | Patient is given 40 mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head. Receives: Drug: Carbetocin |
| Carbetocin 60mcg | Active comparator | Patient is given 60 mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head. Receives: Drug: Carbetocin |
| Carbetocin 80mcg | Active comparator | Patient is given 80 mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head. Receives: Drug: Carbetocin |
| Carbetocin 100mcg | Active comparator | Patient is given 100 mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head. Receives: Drug: Carbetocin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intraoperative requirement for additional uterotonic medication
A request made by the obstetrician performing the cesarean delivery for additional uterotonic medication, due to bleeding or poor uterine tone.
Measured: 1 hour
Secondary outcomes (17)
Uterine tone 2 minutes
Uterine tone, defined as satisfactory or unsatisfactory by the obstetrician at 2 minutes after completion of the carbetocin injection.
Measured: 2 minutes
Uterine tone 5 minutes
Uterine tone, defined as satisfactory or unsatisfactory by the obstetrician at 5 minutes after completion of the carbetocin injection.
Measured: 5 minutes
Additional uterotonics administered
The drug, dosage and timing of any additional uterotonic medication given during surgery.
Measured: 45 minutes
Estimated blood loss
Blood loss will be calculated through the difference in hematocrit values assessed prior to surgery and 24 hours after the cesarean delivery.
Measured: 24 hours
Intravenous fluid administered during surgery
The total volume (ml) of fluid administered from entering the operating room to skin closure.
Measured: 2 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
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 or a heart rate < 50bpm, 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 posted14 Sep 2018
- Study start19 Nov 2018
- Primary completion16 May 2019
- Study completion17 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Model description
- Biased coin up-and-down design.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jose Carvalho, MD, Principal investigator, MOUNT SINAI HOSPITAL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03672045
- Sponsor's protocol ID
- 18-07
- Status last verified
- Jun 2019
- First submitted
- 13 Sep 2018
- Last updated
- 7 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Drew T, Balki M, Farine D, Ye XY, Downey K, Carvalho JCA. Carbetocin at elective caesarean section: a sequential allocation trial to determine the minimum effective dose in obese women. Anaesthesia. 2020 Mar;75(3):331-337. doi: 10.1111/anae.14944. Epub 2019 Dec 22.
PubMed 31867715
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Carbetocin at Elective Cesarean Deliveries: A Dose-finding Study in Women With BMI ≥ 40kg/m2
- ClinicalTrials.gov ID
- NCT03672045
- Acronym / sponsor ID
- 18-07
- Conditions
- Postpartum Hemorrhage
- Keywords
- pregnancy, postpartum hemorrhage, Cesarean delivery, carbetocin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai HospitalUniversity, hospital or other
- Study start
- 19 Nov 2018 (actual)
- Primary completion
- 16 May 2019 (actual)
- Study completion
- 17 May 2019 (actual)
- First posted
- 14 Sep 2018 (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.
Postpartum hemorrhage (PPH) due to uterine atony is a major cause of maternal morbidity and mortality. Carbetocin is a uterotonic with a superior pharmacokinetic profile to oxytocin. In a study performed at Mount Sinai Hospital, the investigators have shown that smaller doses of carbetocin (14.8 mcg) are as effective in achieving adequate uterine tone at elective cesarean section compared to the current recommended dose of 100mcg. However, this study was limited to those women with a body mass index (BMI) of <40 kg/m2. Maternal obesity has been shown to increase the risks of hemorrhage secondary to uterine atony, therefore the investigators wish to perform a dose finding study to determine the ED90 of carbetocin at caesarean section in those women with a BMI>40.
Detailed description
Postpartum hemorrhage (PPH) is one of the leading causes of death during childbirth and accounts for an estimated 140,000 deaths per year worldwide. The World Health Organization (WHO) recommends active management of the third stage of labor to prevent PPH, even in low risk patients. Prophylactic uterotonic drugs administered after delivery are the main element of active management of the third stage and have been demonstrated to reduce the incidence of PPH by up to 40%.
Oxytocin is the most commonly used uterotonic in North America, however it has a very short duration of action and requires a continuous infusion to achieve sustained effect, with large doses associated with adverse effects like low blood pressure, nausea, vomiting, abnormal heart rhythms and changes on ECG. Carbetocin is a synthetic oxytocin analogue. It causes uterine contraction via the same mechanism as oxytocin. Its duration of action is 4 to 7 times that of oxytocin due to an increased biological half-life in plasma and at the oxytocin receptors in the uterus. The Society of Obstetricians and Gynecologists of Canada (SOGC) has recommended a single dose of 100 mcg of carbetocin at elective cesarean delivery to promote uterine contraction. In a study performed at Mount Sinai Hospital, the investigators have shown that smaller doses of carbetocin (14.8 mcg) are effective in achieving adequate uterine tone at elective cesarean section. However this study was limited to those women with a BMI of <40 kg/m2
The prevalence of obesity is increasing in young women and some studies have shown that obese women have higher rates of caesarean delivery compared to non-obese women. Other studies have demonstrated an increased risk of hemorrhage due to poor uterine tone in obese women. Laboratory studies show that BMI alone appears to contribute to blunted uterine muscle responses and therefore contraction responses to oxytocin in obese women. Previous dose finding studies have excluded those women with a BMI of ≥40kgm2. Therefore, the investigators wish to perform a double-blind dose finding study using the biased coin up-and-down sequential allocation technique to determine the ED90 of carbetocin at caesarean section in those women with a BMI>40.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
- Model description
- Biased coin up-and-down design.
| Arm | Type | Receives |
|---|---|---|
| Carbetocin 10mcg | Active comparator | Drug: CarbetocinPatient is given 10 mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head. |
| Carbetocin 20mcg | Active comparator | Drug: CarbetocinPatient is given 20 mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head. |
| Carbetocin 40mcg | Active comparator | Drug: CarbetocinPatient is given 40 mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head. |
| Carbetocin 60mcg | Active comparator | Drug: CarbetocinPatient is given 60 mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head. |
| Carbetocin 80mcg | Active comparator | Drug: CarbetocinPatient is given 80 mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head. |
| Carbetocin 100mcg | Active comparator | Drug: CarbetocinPatient is given 100 mcg of carbetocin intravenously over 1 minute, immediately upon delivery of the fetal head. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- BMI ≥40kg/m2
- Elective cesarean delivery under regional anesthesia
- Gestational age ≥ 37 weeks
- No known additional risk factors for postpartum hemorrhage
- Written informed consent to participate in this study
Key exclusion criteria (5 listed)
- Refusal to give written informed consent
- Allergy or hypersensitivity to carbetocin or oxytocin
- Conditions (other than high BMI) that may predispose to uterine atony and postpartum hemorrhage such as placenta previa, multiple gestation, polyhydramnios, uterine fibroids, previous history of uterine atony and postpartum bleeding, or bleeding diathesis.
- Hepatic, renal, and vascular disease
- Use of general anesthesia prior to the administration of the study drug
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: Duratocincarbetocin administered IV, over 1 minute following delivery of the fetal head | Drug | Carbetocin 100mcg, Carbetocin 10mcg, Carbetocin 20mcg, Carbetocin 40mcg, Carbetocin 60mcg, Carbetocin 80mcg |
Primary outcome
Intraoperative requirement for additional uterotonic medication
Time frame: 1 hour
A request made by the obstetrician performing the cesarean delivery for additional uterotonic medication, due to bleeding or poor uterine tone.
17 secondary outcomes
Uterine tone 2 minutes
Time frame: 2 minutes
Uterine tone 5 minutes
Time frame: 5 minutes
Additional uterotonics administered
Time frame: 45 minutes
Estimated blood loss
Time frame: 24 hours
Intravenous fluid administered during surgery
Time frame: 2 hours
Hypotension: systolic blood pressure less than 80% 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 7 Jun 2019.
- Derived from this study: PubMed 31867715Drew T, Balki M, Farine D, Ye XY, Downey K, Carvalho JCA. Carbetocin at elective caesarean section: a sequential allocation trial to determine the minimum effective dose in obese women. Anaesthesia. 2020 Mar;75(3):331-337. doi: 10.1111/anae.14944. Epub 2019 Dec 22.
- Individual participant dataSharing planned: No
Related trials for Postpartum Hemorrhage
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Measured Versus Hemoglobin-Calculated Postpartum Blood Loss in Waterbirth
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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.
Jose Carvalho, MD principal investigator
MOUNT SINAI HOSPITAL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Carbetocin in people with Postpartum Hemorrhage, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 1 site 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 5 inclusion and 5 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 7 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Intraoperative requirement for additional uterotonic medication (time frame: 1 hour). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03672045, which also lists 1 linked publication.
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 7 Jun 2019.