Oxytocin Pharmacokinetics and Pharmacodynamics

Study Overview
=================
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 a second intravenous (IV) catheter inserted in the contralateral arm to their first IV 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 oxytocin at 2.5 IU/hour immediately after umbilical cord clamping. IV samples will be drawn from the second IV at 0, 1, 2.5, 5, 10, 20, 30, 45, 60 minutes post cord clamping. 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.

Official Title
-----------------
Pharmacokinetics and Pharmacodynamics of Oxytocin in Cesarean Delivery

Conditions
-----------------
Post Partum Hemorrhage, Cesarean Section Complications, Blood Loss

Intervention / Treatment
-----------------
* Drug: deuterated oxytocin (d5OT)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria 18-50 years old intrauterine pregnancy term pregnancy (>/= 37 weeks gestation) scheduled or unscheduled non-emergent cesarean delivery Exclusion Criteria: emergent cesarean delivery allergy to oxytocin inability to provide informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: All subjects will receive a 1 IU bolus of deuterated oxytocin (d5OT) intraoperatively during their cesarean delivery.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxytocin PK/PD Arm<br>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 umbilical cord clamping. | Drug: deuterated oxytocin (d5OT)<br>* Subjects will receive a 1 IU bolus of deuterated oxytocin (d5OT) intraoperatively during their elective cesarean delivery.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline plasma concentrations of deuterated oxytocin | The plasma concentration of deuterium labelled oxytocin at the time of umbilical cord clamping | Intraoperatively (at the time of clamping of the umbilical cord) | 
| Plasma concentrations of deuterated oxytocin at 1 minute | The plasma concentration of deuterium labelled oxytocin at 1 minute post-umbilical cord clamping | Intraoperatively (1 minute following clamping of the umbilical cord) | 
| Plasma concentrations of deuterated oxytocin at 2.5 minutes | The plasma concentration of deuterium labelled oxytocin at 2.5 minutes post-umbilical cord clamping | Intraoperatively (2.5 minutes following clamping of the umbilical cord) | 
| Plasma concentrations of deuterated oxytocin at 5 minutes | The plasma concentration of deuterium labelled oxytocin at 5 minutes post-umbilical cord clamping | Intraoperatively (5 minutes following clamping of the umbilical cord) | 
| Plasma concentrations of deuterated oxytocin at 10 minutes | The plasma concentration of deuterium labelled oxytocin at 10 minutes post-umbilical cord clamping | Intraoperatively (10 minutes following clamping of the umbilical cord) | 
| Plasma concentrations of deuterated oxytocin at 15 minutes | The plasma concentration of deuterium labelled oxytocin at 15 minutes post-umbilical cord clamping | Intraoperatively (15 minutes following clamping of the umbilical cord) | 
| Plasma concentrations of deuterated oxytocin at 20 minutes | The plasma concentration of deuterium labelled oxytocin at 20 minutes post-umbilical cord clamping | Intraoperatively (20 minutes following clamping of the umbilical cord) | 
| Plasma concentrations of deuterated oxytocin at 30 minutes | The plasma concentration of deuterium labelled oxytocin at 30 minutes post-umbilical cord clamping | Intraoperatively (30 minutes following clamping of the umbilical cord) | 
| Plasma concentrations of deuterated oxytocin at 45 minutes | The plasma concentration of deuterium labelled oxytocin at 45 minutes post-umbilical cord clamping | Intraoperatively (45 minutes following clamping of the umbilical cord) | 
| Plasma concentrations of deuterated oxytocin at 60 minutes | The plasma concentration of deuterium labelled oxytocin at 60 minutes post-umbilical cord clamping | Intraoperatively (60 minutes following clamping of the umbilical cord) | 
| 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 clamping of the umbilical cord) | 
| 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 clamping of the umbilical cord) | 
| 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 clamping of the umbilical cord) | 
| 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 clamping of the umbilical cord) | 
| 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 clamping of the umbilical cord) | 
| 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 clamping of the umbilical cord) | 
| 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 clamping of the umbilical cord) | 
| 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 clamping of the umbilical cord) | 
| 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 clamping of the umbilical cord) | 
| 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 clamping of the umbilical cord) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Oxytocin, pharmacokinetics and Pharmacodynamics, Uterine Tone, Postpartum, Elective C-Section, Parturients