Pharmacokinetics of Oxytocin at Cesarean Delivery (Peacocks)

The Pharmacokinetics of Oxytocin in Pregnant Women Undergoing Cesarean Delivery - a Feasibility Pilot Study

The primary objective is to obtain data to inform the design of a population pharmacokinetic study of oxytocin after administration at CD as per standard institutional practice.

Study Overview

• Status: Completed
• Conditions: Postpartum Hemorrhage
• Intervention / Treatment: Drug: oxytocin; Device: Shore durometer

Detailed Description

In this pilot study the investigators will compare plasma oxytocin concentrations measured in arterial and venous blood, after oxytocin administration at cesarean delivery, in order to assess the validity of venous samples. They will also measure oxytocinase to explore how levels vary around the time of delivery of the placenta and to assess the effect that this may have on the metabolism of oxytocin.

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in St. Louis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Pregnant women scheduled for cesarean delivery of their babies at term

Description

Inclusion Criteria:

• Term singleton pregnancy
• Age 18-45 years of age
• ASA classification 2 or 3
• Scheduled cesarean delivery under neuraxial anaesthesia

Exclusion Criteria:

• Age or ASA classification outside of inclusion criteria
• Need for general anaesthesia
• Absence of consent
• Inability to communicate in English or other barrier to providing informed consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
BMI 20 - 29.9 kg/m2	Drug: oxytocin; PK measurements of oxytocin; Device: Shore durometer; The investigators will take serial readings from a digital durometer at the uterine fundus at 3, 6, 9 and 12 minutes following OXT administration to provide data that will inform an estimate of the timing of peak effect. Shore durometers measure the hardness of materials on a scale of 0-100 Shore Units (SU). Preliminary (unpublished) data provided a range of 10-56 SU after oxytocin administration at cesarean delivery. Durometer readings were also shown to correlate positively with the obstetrician's manual assessment of uterine contractility, which is traditionally used to determine the success or failure of uterotonic therapy.
BMI > 30 kg/m2	Drug: oxytocin; PK measurements of oxytocin; Device: Shore durometer; The investigators will take serial readings from a digital durometer at the uterine fundus at 3, 6, 9 and 12 minutes following OXT administration to provide data that will inform an estimate of the timing of peak effect. Shore durometers measure the hardness of materials on a scale of 0-100 Shore Units (SU). Preliminary (unpublished) data provided a range of 10-56 SU after oxytocin administration at cesarean delivery. Durometer readings were also shown to correlate positively with the obstetrician's manual assessment of uterine contractility, which is traditionally used to determine the success or failure of uterotonic therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arterial [OXT]	Concentration of oxytocin in arterial samples	Scheduled samples during the first 30 minutes after oxytocin administration
Venous [OXT]	Concentration of oxytocin in venous samples	Scheduled samples during the first 30 minutes after oxytocin administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arterial [OXTase]	Concentration of oxytocinase in arterial samples	Scheduled samples during the first 30 minutes after oxytocin administration
Uterine tone	Uterine tone measured using a Shore Durometer or assessed by obstetrician using numerical rating score (NRS, 0-10)	Scheduled measurements during the first 30 minutes after oxytocin administration
Hypotension	Incidence of systolic BP reduced by 20% from baseline	Measured intraoperatively
Nausea & Vomiting	Incidence of nausea and vomiting	Recorded intraoperatively
EBL	Estimated blood loss in milliliters	Estimated at the end of surgery

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: David T Monks, MBChB, Washington University School of Medicine

Publications and helpful links

General Publications

• Say L, Chou D, Gemmill A, Tuncalp O, Moller AB, Daniels J, Gulmezoglu AM, Temmerman M, Alkema L. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014 Jun;2(6):e323-33. doi: 10.1016/S2214-109X(14)70227-X. Epub 2014 May 5.
• Attilakos G, Psaroudakis D, Ash J, Buchanan R, Winter C, Donald F, Hunt LP, Draycott T. Carbetocin versus oxytocin for the prevention of postpartum haemorrhage following caesarean section: the results of a double-blind randomised trial. BJOG. 2010 Jul;117(8):929-36. doi: 10.1111/j.1471-0528.2010.02585.x. Epub 2010 May 19.
• Chiou WL. The phenomenon and rationale of marked dependence of drug concentration on blood sampling site. Implications in pharmacokinetics, pharmacodynamics, toxicology and therapeutics (Part II). Clin Pharmacokinet. 1989 Oct;17(4):275-90. doi: 10.2165/00003088-198917040-00005. No abstract available.
• Chiou WL. The phenomenon and rationale of marked dependence of drug concentration on blood sampling site. Implications in pharmacokinetics, pharmacodynamics, toxicology and therapeutics (Part I). Clin Pharmacokinet. 1989 Sep;17(3):175-99. doi: 10.2165/00003088-198917030-00004.

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2019
• Primary Completion (Actual): February 28, 2020
• Study Completion (Actual): February 28, 2020

Study Registration Dates

• First Submitted: March 29, 2019
• First Submitted That Met QC Criteria: March 29, 2019
• First Posted (Actual): April 2, 2019

Study Record Updates

• Last Update Posted (Actual): May 7, 2020
• Last Update Submitted That Met QC Criteria: May 6, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Postpartum Hemorrhage; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: 201810134

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No