Oxytocin Pharmacokinetics and Pharmacodynamics

The University of Chicago

Status and phase: Enrolling; Phase 2

Conditions: Cesarean Section Complications; Blood Loss; Post Partum Hemorrhage

Treatments: Drug: deuterated oxytocin (d5OT)

Study type: Interventional

Funder types: Other

Identifiers

NCT05488457

IRB24-0480

Details and patient eligibility

About

Oxytocin is the first-line drug to promote contraction of the uterus and prevent atony immediately after delivery. Nonetheless, unpredictable uterine atony refractory to oxytocin affects roughly 250,000 parturients annually in the U.S. and rates are increasing. This two-part study will measure the action of oxytocin at cesarean delivery. The first part will measure the pharmacokinetics of a single intravenous (IV) dose of deuterium-labeled oxytocin. The second part will measure the pharmacodynamics of all plasma oxytocin to see how concentrations correspond to the contractile effect on the uterus.

After delivery of the fetus, study subjects will receive a bolus of IV deuterated oxytocin followed by an unlabeled oxytocin infusion. Venous blood samples drawn at multiple time points (within 1 hour after delivery) will be analyzed for plasma concentrations of labeled and unlabeled (endogenous + exogenous infused) oxytocin over time. Plasma concentrations will be compared with 0-10 uterine tone scores measuring uterine contraction strength, to describe the concentration-effect relationship.

The goal of this study is to define both the pharmacokinetics and pharmacodynamics of oxytocin in parturients to help identify the cause(s) of failed first-line oxytocin therapy.

Full description

Parturients aged 18-50 with an intrauterine term pregnancy (37 weeks or greater) undergoing non-emergent cesarean delivery at the University of Chicago (UC) and Stanford University will be recruited.

Methods: All subjects will receive standard pre-, intra- and postoperative care for their cesarean delivery with additional study interventions.

Study subjects will have an additional intravenous (IV) catheter inserted for intra-operative study-related blood draws.

A single, 1 International Unit (IU) bolus of deuterated oxytocin (d5OT) will be given to the subject, followed by an infusion of standard protocol oxytocin immediately after placental delivery. IV samples will be drawn from the study IV at 0, 1, 2.5, 5, 10, 20, 30, 45, 60 minutes following administration of the study drug. The samples will be processed, batched and shipped to the central lab being used in this study. Uterine tone scores will be measured simultaneously with blood draws until accurate palpation is no longer possible. Uterine tone score is a 0 to 10 numeric rating scale with 0 to describe unsatisfactory or no uterine tone and 10 to describe perfect uterine tone.

Enrollment: 100 estimated patients

Sex: Female

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• 18-50 years old
• intrauterine pregnancy
• term (>39 weeks gestation or 37-39 weeks gestation with fetal or maternal medical indication for delivery) pregnancy
• non-emergent (scheduled or unscheduled) cesarean delivery

Exclusion Criteria:

• allergy or contraindication to oxytocin
• inability to provide informed consent

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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100 participants in 1 patient group

Oxytocin PK/PD Arm

Experimental group

Description:

Eligible subjects will receive a single, 1 IU bolus of deuterated oxytocin (d5OT) intra-operatively, followed by an infusion of standard therapeutic d0 oxytocin immediately after placental delivery.

Treatment:

Drug: deuterated oxytocin (d5OT)