Clinical trial NCT05488457: Oxytocin Pharmacokinetics and Pharmacodynamics
Official title: Pharmacokinetics and Pharmacodynamics of Oxytocin in Cesarean Delivery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Post Partum Hemorrhage
Cesarean Section Complications
Blood Loss
Keywords: Oxytocin
pharmacokinetics and Pharmacodynamics
Uterine Tone
Postpartum
Elective C-Section
Parturients
Lead sponsor: University of Chicago
Sponsor class: OTHER
Collaborators: name: Stanford University
First posted: 2022-08-04
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All subjects will receive a 1 IU bolus of deuterated oxytocin (d5OT) intraoperatively during their cesarean delivery.
Primary purpose: PREVENTION

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Baseline plasma concentrations of deuterated oxytocin
timeFrame: Intraoperatively (prior to delivery)
measure: Plasma concentrations of deuterated oxytocin at 1 minute
timeFrame: Intraoperatively (1 minute following study drug administration)
measure: Plasma concentrations of deuterated oxytocin at 2.5 minutes
timeFrame: Intraoperatively (2.5 minutes following study drug administration)
measure: Plasma concentrations of deuterated oxytocin at 5 minutes
timeFrame: Intraoperatively (5 minutes following study drug administration)
measure: Plasma concentrations of deuterated oxytocin at 10 minutes
timeFrame: Intraoperatively (10 minutes following study drug administration)
measure: Plasma concentrations of deuterated oxytocin at 15 minutes
timeFrame: Intraoperatively (15 minutes following study drug administration)
measure: Plasma concentrations of deuterated oxytocin at 20 minutes
timeFrame: Intraoperatively (20 minutes following study drug administration)
measure: Plasma concentrations of deuterated oxytocin at 30 minutes
timeFrame: Intraoperatively (30 minutes following study drug administration)
measure: Plasma concentrations of deuterated oxytocin at 45 minutes
timeFrame: Intraoperatively (45 minutes following study drug administration)
measure: Plasma concentrations of deuterated oxytocin at 60 minutes
timeFrame: Intraoperatively (60 minutes following study drug administration)
measure: 0-10 Uterine Tone Score
timeFrame: Intraoperatively (at the time of study drug administration)
measure: 0-10 Uterine Tone Score
timeFrame: Intraoperatively (1 minute following study drug administration)
measure: 0-10 Uterine Tone Score
timeFrame: Intraoperatively (2.5 minutes following study drug administration)
measure: 0-10 Uterine Tone Score
timeFrame: Intraoperatively (5 minutes following study drug administration)
measure: 0-10 Uterine Tone Score
timeFrame: Intraoperatively (10 minutes following study drug administration)
measure: 0-10 Uterine Tone Score
timeFrame: Intraoperatively (15 minutes following study drug administration)
measure: 0-10 Uterine Tone Score
timeFrame: Intraoperatively (20 minutes following study drug administration)
measure: 0-10 Uterine Tone Score
timeFrame: Intraoperatively (30 minutes following study drug administration)
measure: 0-10 Uterine Tone Score
timeFrame: Intraoperatively (45 minutes following study drug administration)
measure: 0-10 Uterine Tone Score
timeFrame: Intraoperatively (60 minutes following study drug administration)
Secondary outcomes:
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
Study officials:
affiliation: University of Chicago
name: Naida M Cole, MD
role: PRINCIPAL_INVESTIGATOR
References: