Oxytocin Pharmacokinetics and Pharmacodynamics

Cesarean Section Complications Clinical Trial

Official title:

Pharmacokinetics and Pharmacodynamics of Oxytocin in Cesarean Delivery

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05488457
• Other study ID #: IRB24-0480
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 1, 2024
• Est. completion date: December 31, 2025

Study information

• Verified date: April 2024
• Source: University of Chicago
• Contact: Naida M Cole, MD
• Phone: 773-702-6700
• Email: nmcole[@]bsd.uchicago.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: December 31, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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

• non-English speaking

Related Conditions & MeSH terms

• Blood Loss
• Cesarean Section Complications
• Hemorrhage
• Post Partum Hemorrhage
• Postpartum Hemorrhage

Intervention

Drug:
• deuterated oxytocin (d5OT)
Subjects will receive a 1 IU bolus of deuterated oxytocin (d5OT) intraoperatively during their nonemergent cesarean delivery.

Locations

Country	Name	City	State
United States	University of Chicago	Chicago	Illinois
United States	Stanford University	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
University of Chicago	Lucile Packard Children's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Baseline plasma concentrations of deuterated oxytocin	The plasma concentration of deuterium labelled oxytocin at baseline	Intraoperatively (prior to delivery)
Primary	Plasma concentrations of deuterated oxytocin at 1 minute	The plasma concentration of deuterium labelled oxytocin at 1 minute post-study drug	Intraoperatively (1 minute following study drug administration)
Primary	Plasma concentrations of deuterated oxytocin at 2.5 minutes	The plasma concentration of deuterium labelled oxytocin at 2.5 minutes post-study drug	Intraoperatively (2.5 minutes following study drug administration)
Primary	Plasma concentrations of deuterated oxytocin at 5 minutes	The plasma concentration of deuterium labelled oxytocin at 5 minutes post-study drug	Intraoperatively (5 minutes following study drug administration)
Primary	Plasma concentrations of deuterated oxytocin at 10 minutes	The plasma concentration of deuterium labelled oxytocin at 10 minutes post-study drug	Intraoperatively (10 minutes following study drug administration)
Primary	Plasma concentrations of deuterated oxytocin at 15 minutes	The plasma concentration of deuterium labelled oxytocin at 15 minutes post-study drug	Intraoperatively (15 minutes following study drug administration)
Primary	Plasma concentrations of deuterated oxytocin at 20 minutes	The plasma concentration of deuterium labelled oxytocin at 20 minutes post-study drug	Intraoperatively (20 minutes following study drug administration)
Primary	Plasma concentrations of deuterated oxytocin at 30 minutes	The plasma concentration of deuterium labelled oxytocin at 30 minutes post-study drug	Intraoperatively (30 minutes following study drug administration)
Primary	Plasma concentrations of deuterated oxytocin at 45 minutes	The plasma concentration of deuterium labelled oxytocin at 45 minutes post-study drug	Intraoperatively (45 minutes following study drug administration)
Primary	Plasma concentrations of deuterated oxytocin at 60 minutes	The plasma concentration of deuterium labelled oxytocin at 60 minutes post-study drug	Intraoperatively (60 minutes following study drug administration)
Primary	0-10 Uterine Tone Score	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.	Intraoperatively (at the time of study drug administration)
Primary	0-10 Uterine Tone Score	Uterine tone 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.	Intraoperatively (1 minute following study drug administration)
Primary	0-10 Uterine Tone Score	Uterine tone 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.	Intraoperatively (2.5 minutes following study drug administration)
Primary	0-10 Uterine Tone Score	Uterine tone 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.	Intraoperatively (5 minutes following study drug administration)
Primary	0-10 Uterine Tone Score	Uterine tone 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.	Intraoperatively (10 minutes following study drug administration)
Primary	0-10 Uterine Tone Score	Uterine tone 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.	Intraoperatively (15 minutes following study drug administration)
Primary	0-10 Uterine Tone Score	Uterine tone 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.	Intraoperatively (20 minutes following study drug administration)
Primary	0-10 Uterine Tone Score	Uterine tone 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.	Intraoperatively (30 minutes following study drug administration)
Primary	0-10 Uterine Tone Score	Uterine tone 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.	Intraoperatively (45 minutes following study drug administration)
Primary	0-10 Uterine Tone Score	Uterine tone 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.	Intraoperatively (60 minutes following study drug administration)