Sublingual Oxytocin for the Prevention of Post-partum Hemorrhage

Official title

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

Overview

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.

Detailed description

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.

Interventions

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

Primary outcome measures

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

Secondary outcome measures (10)

• Proportion of participants with satisfactory uterine tone [Time frame: 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 [Time frame: 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 [Time frame: Up to 24 hours after administration of the drug]
• Incidence of blood transfusion due to PPH [Time frame: At 24 hours after administration of the drug]
• Incidence of laparotomy for the treatment of PPH [Time frame: At 24 hours after administration of the drug]
• Proportion of participants that achieve cessation of active bleeding [Time frame: Within 20 minutes after administration of the drug]
• Time to PPH onset [Time frame: Immediately after the intervention up to 24 hours post intervention]
• Time to active bleeding cessation [Time frame: Immediately after the intervention up to 24 hours post intervention]
• Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: 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 [Time frame: 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]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Nigeria · 1 center

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

Identifiers

NCT: NCT06968481 · EX005-201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗