Oxytocin Bolus Versus Infusion in Elective Cesarean Section" (INBOX)

Randomized Double-Blinded Clinical Trial of Oxytocin Bolus Versus Infusion in Elective Cesarean Section

Bolus administration of oxytocin is superior to infusion in time to achieving adequate uterine tone.

Study Overview

• Status: Recruiting
• Conditions: Elective Cesarean Section
• Intervention / Treatment: Drug: Oxytocin bolus or oxytocin infusion

Detailed Description

Oxytocin is the most commonly used uterotonic agent worldwide to achieve adequate uterine tone and prevent postpartum hemorrhage. Over the past decade, the trend has been towards lowering the dose to reduce oxytocin-related adverse effects including nausea, hypotension, chest pain, EKG changes, and maternal death. However, the optimal strategy for oxytocin administration remains controversial. Prior literature found bolus doses less than 5 IU to be effective in achieving adequate uterine tone with a significant reduction in adverse side effects. There is limited high quality data comparing bolus versus infusion administration of oxytocin. The current standard of care at the institution is an infusion of oxytocin 18 IU/hour (0.3 IU/min) and has been proven to be effective in achieving adequate uterine tone. However, the time to uterine tone appears to be slightly longer (3-4 mins) with the infusion method. Given that the estimated uterine blood flow is between 500-700 mls/min, the uterus can lose a significant amount of blood per second if uterine tone is not achieved quickly. Thus, the purpose of this research study is to compare bolus and infusion administration of oxytocin on parturients undergoing elective cesarean section. The primary objective of this study is to test the hypothesis that administration by bolus (vs. standard of care infusion) results in more rapid achievement of adequate uterine tone. Secondary objectives include determining estimated blood loss, prevalence of hypotension, nausea, vomiting, and patient satisfaction.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Tifany E Angelo, DO; Phone Number: 42975 631-444-2975; Email: mailto:Tiffany.Angelo@stonybrookmedicine.edu
• Study Contact Backup: Name: Ayesha Khan; Phone Number: 42120 6314447339; Email: ayesha.khan@stonybrookmedicine.edu

Study Locations

• United States
  • New York
    • Stony Brook, New York, United States, 11794-8167
      • Recruiting
      • Stony Brook University
      • Contact: Ayesha Kham; Phone Number: 631-444-7339; Email: ayesha.khan@stonybrookmedicine.edu
      • Contact: TIFFANY ANGELO, DO; Phone Number: 6314442975; Email: Tiffany.Angelo@stonybrookmedicine.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Parturients between the ages of 18 to 45 with singleton pregnancies
• Undergoing elective cesarean section under spinal anesthesia
• American Society of Anesthesia (ASA) physical status class I or II
• Patients must be able to provide written informed consent

Exclusion Criteria:

• Parturients in labor or ruptured membranes
• Multiple gestation
• Risk factors predisposing to uterine atony (history of placenta previa, preeclampsia, diabetes mellitus macrosomia, hydramnios, bleeding diathesis, uterine fibroids)
• History of uterine atony or postpartum hemorrhage
• History of inherited or acquired coagulation disorders, thrombocytopenia (platelet count <100), or anemia (hemoglobin < 8)
• History of allergy to oxytocin
• Patients not alert and orientated to person, place, and date. Patient must have, in the investigator's opinion, the physical and mental capacity to answer survey questions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bolus arm; Patients will receive 3 IU oxytocin IV bolus over 15 seconds after delivery of the baby/uterine cord clamping and a maintenance infusion of 0.9% Saline will be started at 225ml/hr. If uterine tone is inadequate after 3 minutes, a second bolus of 3 IU oxytocin will be given. If uterine tone is inadequate after an additional 3 minutes, a third bolus of 3 IU Oxytocin IV is given over 15 seconds. If after an additional 3 mins uterine tone is still inadequate, a second infusion consisting of oxytocin 3 IU/hr is started at 100ml/hrs and continued for a total of 4 hours, second line uterotonic agents (Methergine, Hemabate and/ or Cytotec) will be given, and the maintenance 0.9% Saline infusion will be changed to 450 ml/hr for a total of 1 hour, then changed to 38 ml/ hour for the following 3 hours. If uterine tone is considered adequate at 3, 6 or 9 minutes, a second infusion of oxytocin 3 IU/hr (100ml/hr) is started and maintained for 4 hours.	Drug: Oxytocin bolus or oxytocin infusion; On the day of surgery, the patients will be randomized to either bolus or infusion administration of oxytocin. On the day of the procedure, periprocedural data and patient satisfaction (single question) will be recorded.
Active Comparator: Infusion arm; Patients will receive a bolus of IV 0.9% Saline over 15 seconds after delivery of the baby/uterine cord clamping and a maintenance infusion of 18 IU/hr Oxytocin IV (225ml/hr). If uterine tone is inadequate after 3 minutes, a second bolus of 0.9% Saline will be given. If uterine tone is inadequate after another 3 minutes, a third bolus of 0.9% Saline will be given. If after another 3 mins uterine tone is inadequate, a second infusion of 0.9% Saline will be started for 4 hours, second line uterotonic agents (Methergine, Hemabate and/or Cytotec) will be given, and the Oxytocin infusion will be changed to 36 IU/hour (450 ml/hr) for a total of 1 hour, and then changed to 38 ml/hr for the following 3 hours. If uterine tone is considered adequate at 3, 6 or 9 minutes, a second infusion of 0.9% Saline at 100 ml/hr will be started and maintained for 4 hours, along with the maintenance infusion of 18 IU/hr (225 ml/ hr) for a total of 1 hour, then changed to 38 ml/hr for an additional 3 hours.	Drug: Oxytocin bolus or oxytocin infusion; On the day of surgery, the patients will be randomized to either bolus or infusion administration of oxytocin. On the day of the procedure, periprocedural data and patient satisfaction (single question) will be recorded.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number/Proportion of Participants with Adequate Uterine tone	Adequacy of uterine tone (yes/no) at 2 minutes after the baby is born/umbilical cord clamped.	2 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient satisfaction questionnaire (Scale 0 to 10, 0 being complete dissatisfaction and 10 being highly satisfied	Patients will complete a questionnaire 2± 1 hours after surgery	2± 1 hours after surgery

Collaborators and Investigators

• Sponsor: Stony Brook University
• Investigators: Principal Investigator: Tiffany E Angelo, DO, Stony Brook University

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.
• Balki M, Tsen L. Oxytocin protocols for cesarean delivery. Int Anesthesiol Clin. 2014 Spring;52(2):48-66. doi: 10.1097/AIA.0000000000000016. No abstract available.
• Terblanche N, Otahal P, Messmer A, Wright P, Patel S, Nathan K, Sharman JE. An observational cohort study of 3 units versus 5 units slow intravenous bolus oxytocin in women undergoing elective caesarean delivery. J Physiol Pharmacol. 2017 Aug;68(4):547-553.
• Fuchs AR, Fuchs F, Husslein P, Soloff MS. Oxytocin receptors in the human uterus during pregnancy and parturition. Am J Obstet Gynecol. 1984 Nov 15;150(6):734-41. doi: 10.1016/0002-9378(84)90677-x.
• Joseph J, George SK, Daniel M, Ranjan RV. A randomised double-blind trial of minimal bolus doses of oxytocin for elective caesarean section under spinal anaesthesia: Optimal or not? Indian J Anaesth. 2020 Nov;64(11):960-964. doi: 10.4103/ija.IJA_377_20. Epub 2020 Nov 1.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2022
• Primary Completion (Estimated): December 15, 2024
• Study Completion (Estimated): December 15, 2024

Study Registration Dates

• First Submitted: December 23, 2021
• First Submitted That Met QC Criteria: February 2, 2022
• First Posted (Actual): February 11, 2022

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Oxytocin, bolus, infusion
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: IRB 2021-00558

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data will not be shared

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No