Carbetocin vs. Oxytocin at Elective Cesarean Section

Carbetocin vs. Oxytocin at Elective Cesarean Section: a Double-blind, Randomized Controlled Non-inferiority Trial of High and Low Dose Regimens

Patrocinadores

Patrocinador principal: Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Fuente Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Resumen breve

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.

Descripción detallada

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.

Estado general Recruiting
Fecha de inicio May 25, 2017
Fecha de Terminación June 2020
Fecha de finalización primaria June 2020
Fase N/A
Tipo de estudio Interventional
Resultado primario
Medida Periodo de tiempo
Uterine Tone 2 minutes 2 minutes
Resultado secundario
Medida Periodo de tiempo
Uterine Tone 5 minutes 5 minutes
Uterine Tone 10 minutes 10 minutes
Additional uterotonics - operating room 1 hour
Additional uterotonics - 24 hours 24 hours
Estimated blood loss 24 hours
Hypotension: systolic blood pressure less than 80% of baseline 2 hours
Hypertension: systolic blood pressure greater than 120% of baseline 2 hours
Tachycardia: heart rate greater than 130% of baseline 2 hours
Bradycardia: heart rate less than 70% of baseline 2 hours
Presence of ventricular tachycardia: ECG 2 hours
Presence of atrial fibrillation: ECG 2 hours
Presence of atrial flutter: ECG 2 hours
Presence of nausea: questionnaire 2 hours
Presence of vomiting: questionnaire 2 hours
Presence of chest pain: questionnaire 2 hours
Presence of shortness of breath: questionnaire 2 hours
Presence of headache: questionnaire 2 hours
Presence of flushing: questionnaire 2 hours
Inscripción 250
Condición
Intervención

Tipo de intervención: Drug

Nombre de intervención: Carbetocin

Descripción: Patient is given carbetocin (20 or 100 mcg) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.

Otro nombre: Duratocin

Tipo de intervención: Drug

Nombre de intervención: Oxytocin

Descripción: Patient is given oxytocin (0.5 or 5 IU) intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.

Otro nombre: Pitocin

Elegibilidad

Criterios:

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.

Género: Female

Edad mínima: 18 Years

Edad máxima: 50 Years

Voluntarios Saludables: Accepts Healthy Volunteers

Oficial general
Apellido Papel Afiliación
Mrinalini Balki, MD Principal Investigator MOUNT SINAI HOSPITAL
Contacto general

Apellido: Mrinalini Balki, MD

Teléfono: 416-586-4800

Teléfono Ext.: 5270

Email: [email protected]

Ubicación
Instalaciones: Estado: Contacto: Copia de seguridad de contactos: Investigador:
McMaster University Medical Centre (MUMC) | Hamilton, Ontario, L8N 3Z5, Canada Recruiting Daniel Cordovani, MD 905-521-2100 75150 [email protected] Daniel Cordovani, MD Principal Investigator Michelle Morais, MD Sub-Investigator
Mount Sinai Hospital | Toronto, Ontario, M5G1X5, Canada Recruiting Mrinalini Balki, MD 416-586-4800 5270 [email protected] Jose CA Carvalho, MD Sub-Investigator Abdulla Sadiq, MD Sub-Investigator Farine Dan, MD Sub-Investigator Downey Kristi, MSc Sub-Investigator Xiang Ye, MSc Sub-Investigator
Ubicacion Paises

Canada

Fecha de verificación

January 2020

Fiesta responsable

Tipo: Sponsor

Palabras clave
Tiene acceso ampliado No
Condición Examinar
Número de brazos 4
Grupo de brazo

Etiqueta: Carbetocin 20mcg

Tipo: Active Comparator

Descripción: Carbetocin 20mcg, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.

Etiqueta: Carbetocin 100mcg

Tipo: Active Comparator

Descripción: Carbetocin 100mcg, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.

Etiqueta: Oxytocin 0.5IU

Tipo: Active Comparator

Descripción: Oxytocin 0.5IU, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.

Etiqueta: Oxytocin 5IU

Tipo: Active Comparator

Descripción: Oxytocin 5IU, administered intravenously over 1 minute, immediately upon delivery of the anterior shoulder of the baby.

Datos del paciente No
Información de diseño del estudio

Asignación: Randomized

Modelo de intervención: Parallel Assignment

Propósito primario: Treatment

Enmascaramiento: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Fuente: ClinicalTrials.gov