Blood Loss, Cesarean Section Complications, Post Partum Hemorrhage
Conditions
Keywords
Oxytocin, pharmacokinetics and Pharmacodynamics, Uterine Tone, Postpartum, Elective C-Section, Parturients
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.
Interventions
DRUGdeuterated oxytocin (d5OT)
Subjects will receive a 1 IU bolus of deuterated oxytocin (d5OT) intraoperatively during their nonemergent cesarean delivery.
Sponsors
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
All subjects will receive a 1 IU bolus of deuterated oxytocin (d5OT) intraoperatively during their cesarean delivery.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma concentrations of deuterated oxytocin at 10 minutes | Intraoperatively (10 minutes following study drug administration) | The plasma concentration of deuterium labelled oxytocin at 10 minutes post-study drug |
| Plasma concentrations of deuterated oxytocin at 15 minutes | Intraoperatively (15 minutes following study drug administration) | The plasma concentration of deuterium labelled oxytocin at 15 minutes post-study drug |
| Plasma concentrations of deuterated oxytocin at 20 minutes | Intraoperatively (20 minutes following study drug administration) | The plasma concentration of deuterium labelled oxytocin at 20 minutes post-study drug |
| Plasma concentrations of deuterated oxytocin at 30 minutes | Intraoperatively (30 minutes following study drug administration) | The plasma concentration of deuterium labelled oxytocin at 30 minutes post-study drug |
| Plasma concentrations of deuterated oxytocin at 45 minutes | Intraoperatively (45 minutes following study drug administration) | The plasma concentration of deuterium labelled oxytocin at 45 minutes post-study drug |
| Plasma concentrations of deuterated oxytocin at 60 minutes | Intraoperatively (60 minutes following study drug administration) | The plasma concentration of deuterium labelled oxytocin at 60 minutes post-study drug |
| 0-10 Uterine Tone Score | Intraoperatively (at the time of study drug administration) | Uterine tone will be ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling. |
| Baseline plasma concentrations of deuterated oxytocin | Intraoperatively (prior to delivery) | The plasma concentration of deuterium labelled oxytocin at baseline |
| Plasma concentrations of deuterated oxytocin at 1 minute | Intraoperatively (1 minute following study drug administration) | The plasma concentration of deuterium labelled oxytocin at 1 minute post-study drug |
| Plasma concentrations of deuterated oxytocin at 2.5 minutes | Intraoperatively (2.5 minutes following study drug administration) | The plasma concentration of deuterium labelled oxytocin at 2.5 minutes post-study drug |
| Plasma concentrations of deuterated oxytocin at 5 minutes | Intraoperatively (5 minutes following study drug administration) | The plasma concentration of deuterium labelled oxytocin at 5 minutes post-study drug |
Countries
United States
Contacts
CONTACTNaida M Cole, MD
CONTACTSomayeh Mohammadi
PRINCIPAL_INVESTIGATORNaida M Cole, MD
University of Chicago
Outcome results
None listed