Oxytocin Bolus Versus Infusion in High-Risk Patients Undergoing Elective Cesarean Section (INBOX-HR)

Official title

Randomized Double-Blinded Clinical Trial of Oxytocin Bolus Versus Infusion in High-Risk Patients Undergoing Elective Cesarean Section

Overview

The goal of this randomized, double-blind clinical trial is to learn if Oxytocin is most effective at achieving adequate uterine tone (important for preventing postpartum hemorrhage) when administered as a bolus or an infusion in patients at high-risk for postpartum hemorrhage in elective cesarean sections. The main questions that will be answered are: 1. Is Oxytocin bolus more effective than Oxytocin infusion at achieving adequate uterine tone at 2 minutes after the baby is born and every minute thereafter? 2. Does Oxytocin bolus cause less maternal side effects than Oxytocin infusion? 3. Does Oxytocin bolus result in less blood loss than Oxytocin infusion in high risk for postpartum hemorrhage patients undergoing elective cesarean sections? 3\. Are patients more satisfied with their cesarean section when they receive Oxytocin bolus or Oxytocin infusion? Researchers will compare the 2 methods of Oxytocin administration, bolus versus infusion, to see which method is more effective or if they are equally effective. Participants will: 1. Be randomized to receive either Oxytocin bolus or Oxytocin infusion during their cesarean section but after the baby is born. 2. Be asked a question about their experience 2 hours after the surgery. 3. Allow the research team to collect information about how they are doing from their hospital medical records.

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. A prior study was conducted at Stony Brook University Hospital which investigated the difference between bolus versus infusion administration of oxytocin in elective cesarean section patients with a low risk of postpartum hemorrhage (PPH); the results of this randomized, double blinded clinical trial showed that bolus was not superior for adequate uterine tone at 2 minutes when compared to infusion of oxytocin, but blood loss was modestly lower and total oxytocin exposure was substantially lower in the bolus arm. Which makes the most logical next question: Does bolus oxytocin become more clinically meaningful in patients with higher baseline risk for uterine atony or hemorrhage. The investigators aim to address this question with the INBOX-HR study.

INBOX-HR acts as a continuing investigation on the difference between bolus versus infusion administration of oxytocin, specifically for patients that are at a high risk for postpartum hemorrhage. Thus, the purpose of this research study is to compare bolus and infusion administration of oxytocin on parturients at high risk for postpartum hemorrhage undergoing elective cesarean section. The primary objective of this study is to test the hypothesis that administration by bolus vs. infusion results in more rapid achievement of adequate uterine tone in this patient population. Secondary objectives include determining estimated blood loss, prevalence of hypotension, change in heart rate, nausea, vomiting, and patient satisfaction, and 0 - 10 uterine tone score.

Interventions

• Drug Oxytocin Bolus or Oxytocin Infusion
  On the day of surgery, patients will be randomized to receive either bolus or infusion administration of Oxytocin. On the day of the procedure, periprocedural data and patient satisfaction (single question) will be recorded.

Primary outcome measures

• Time to uterine tone [Time frame: 2 minutes after umbilical cord clamp until 10 minutes.]

Secondary outcome measures (8)

• Estimated intraoperative blood loss [Time frame: From the start to end of surgery]
• Changes in heart rate (beats per minute) [Time frame: During uterine cord clamp and every 2 minutes thereafter until 10 minutes]
• Changes in blood pressure (mmHg) [Time frame: During uterine cord clamp and every 2 minutes thereafter until 10 minutes.]
• Total dose of phenylephrine administered intraoperatively [Time frame: From the start to end of surgery]
• Participants with need for additional uterotonic agents [Time frame: From oxytocin administration until end of surgery]
• 0-10 Uterine tone score [Time frame: 2 minutes after uterine cord clamping until 10 minutes.]
• Participants with maternal side effects [Time frame: From oxytocin administration until end of surgery]
• Patient satisfaction questionnaire [Time frame: 2 hours after surgery]

Eligibility criteria

Inclusion criteria

• Undergoing elective cesarean section under spinal anesthesia or combined spinal anesthesia (CSE)
• Patients must be able to provide written informed consent in either English or Spanish
• Parturient classified as high risk for postpartum hemorrhage as defined by the adapted California Maternal Quality Care Obstetric Hemorrhage Risk Screen

Exclusion criteria

• Parturient in labor or ruptured membranes
• Patient does not possess the physical and mental capacity to provide informed consent
• Urgent or emergent cesarean sections
• Patients with a known major coagulopathy
• Patients with significant thrombocytopenia limiting neuraxial anesthesia (<70k)
• Patients on therapeutic anticoagulation at time of procedure
• Patients on the placenta accreta spectrum
• Patients with severe cardiac disease contraindicating oxytocin
• Patients with an allergy to oxytocin

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Other

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Wang LY, Wang J, Dong JH, Ping ZP, Chen XZ, Wei CN. The optimal oxytocin infusion rate for preventing uterine atony during cesarean delivery in elderly parturients with prior history of cesarean delivery. Front Pharmacol. 2023 Jul 28;14:1211693. doi: 10.3389/fphar.2023.1211693. eCollection 2023. PMID 37576820
• Oyelese Y, Ananth CV. Postpartum hemorrhage: epidemiology, risk factors, and causes. Clin Obstet Gynecol. 2010 Mar;53(1):147-56. doi: 10.1097/GRF.0b013e3181cc406d. PMID 20142652
• 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. PMID 33487681
• 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. PMID 6093538
• 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. PMID 29151071
• 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. PMID 24667448
• 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. PMID 25103301

Identifiers

NCT: NCT07688512 · IRB2026-00322

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗