Sublingual Oxytocin for the Prevention of Post-partum Hemorrhage

Официальное название

Phase 2, Open-label, Randomized, Dose Ascending Trial to Evaluate the Efficacy and Safety of Sublingual Oxytocin for the Prevention of Post-partum Hemorrhage Caused by Uterine Atony in Term Pregnant Women With Uncomplicated Vaginal Delivery

Обзор

An open-label, randomized, single-center, dose ascending trial will be conducted to evaluate the efficacy and safety of sublingual oxytocin for the prevention of post-partum hemorrhage caused by uterine atony in term pregnant women having an uncomplicated vaginal delivery.

Подробное описание

The primary objective is to estimate the optimal effective dose (ED90) of sublingual oxytocin administered during the active management of the third stage of labor to result in satisfactory uterine tone and a cumulative blood loss \< 500 ml at 20 minutes after vaginal delivery in 90% of parturients with an acceptable safety profile.

Вмешательства

• Препарат Oxytocin sublingual
  Sublingual oxytocin 1000 IU, 3000 IU or 6000 IU
• Препарат Oxytocin IM
  Intramuscular oxytocin 10 IU

Первичные конечные точки

• Proportion of participants with a satisfactory uterine tone and cumulative blood loss < 500 ml [Срок оценки: From administration of the drug to 20 minutes post-partum]

Вторичные конечные точки (10)

• Proportion of participants with satisfactory uterine tone [Срок оценки: after 3 min, 5 min, 10 min, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 12 hours and 24 hours after administration of the drug]
• Measurement of blood loss [Срок оценки: 3 min, 5 min, 10 min, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 12 hours and 24 hours after administration of the drug]
• Proportion of participants who develop primary PPH [Срок оценки: Up to 24 hours after administration of the drug]
• Incidence of blood transfusion due to PPH [Срок оценки: At 24 hours after administration of the drug]
• Incidence of laparotomy for the treatment of PPH [Срок оценки: At 24 hours after administration of the drug]
• Proportion of participants that achieve cessation of active bleeding [Срок оценки: Within 20 minutes after administration of the drug]
• Time to PPH onset [Срок оценки: Immediately after the intervention up to 24 hours post intervention]
• Time to active bleeding cessation [Срок оценки: Immediately after the intervention up to 24 hours post intervention]
• Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: From the time of written informed consent until the End of Study visit and must be followed up until resolution or stabilization]
• Absolute number and percentage of participants with oral irritation/inflammation and abrasion [Срок оценки: after admission to hospital (during the Latent or Active phase for all participants) and at 20 minutes and 24 hours post dose for participants who are administered the investigational drug]

Критерии участия

Критерии включения

• Women willing and able to provide Informed consent.
• Women who are able to understand, confirm and give informed consent during an antenatal visit or first stage of labor (cervical dilation <6 cm).
• Healthy, primiparous or multiparous (2-4 deliveries), term-pregnant female with a gestational age of 37 to 42 weeks (inclusive). Gestational age should be confirmed with an obstetrical ultrasound if available.
• Aged between 18 and 40 years (both inclusive).
• Confirmed singleton pregnancy.
• Based on the Investigator assessment, maternal and fetal conditions are met to expect a vaginal delivery.
• For participants in the PK subgroup: women with baseline hemoglobin level ≥11 g/dL.

Критерии исключения

• Women who are unable to provide written Informed consent.
• Women undergoing an elective or emergency cesarean section.
• Conditions predisposing to uterine atony and PPH (e.g., previous PPH, placenta praevia, multiple gestation, severe pre-eclampsia, polyhydramnios, uterine fibroids, need for induction of labor, bleeding diathesis, sepsis, body mass index \[BMI\] ˃ 30 kg/m2 , macrosomia with estimated fetal weight >4500 g, if antenatal ultrasound was performed).
• Women with moderate or severe anemia (defined as Hb <10 g/dL).
• Women who have undergone female genital mutilation.
• Known allergies to carbetocin, other oxytocin homologues or excipients in the medicinal products used in the trial.
• Oral conditions before administration of sublingual oxytocin such as moderate erythema and edema, severe irritation/inflammation, moderate or severe abrasion.
• Conditions predisposing to myocardial ischemia due to pre-existing cardiovascular diseases (such as hypertrophic cardiomyopathy, valvular heart disease and/or ischemic heart disease, including vasospasm of the coronary arteries) or known long QT syndrome or related symptoms.
• Any clinically significant abnormality following review of medical history, laboratory result and physical examination at screening as judged by the Investigator (e.g., severe anemia, antepartum hemorrhage, mental disorder, history of cervical cancer or history of severe infection of the uterus, religious beliefs prohibiting blood transfusions).
• Previous surgery of the cervix or uterus or any other preexisting condition that could interfere with the measurement of uterine contractility.
• Current use or use within 30 days before the start of the IMP or reference product of one or more of predefined medications

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

Nigeria · 1 центр

• Africa Center of Excellence for Population Health and Policy — Kano

Идентификаторы

NCT: NCT06968481 · EX005-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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