Stopping Opioid Overuse in Obstetrics To Halt Exposure Trial (SOOOTHE)

Stopping Opioid Overuse in Obstetrics to Halt Exposure Trial

As the opioid epidemic continues on, more research is needed on multi-modal approaches to decrease opioid exposure after common procedures. The aim of this study is to investigate the role of a transverses abdominis block using liposome bupivacaine suspension in reducing use of opioid medications through post-operative day 7. The study is a proposed double-blind, randomized controlled trial.

Study Overview

• Status: Enrolling by invitation
• Conditions: Pain, Postoperative; Opioid Use
• Intervention / Treatment: Drug: Liposomal bupivacaine; Procedure: TAP block; Drug: Deposition of saline

Detailed Description

Nearly 1 in 3 women in the US deliver by cesarean delivery. After cesarean delivery, approximately 75-87% percent of women are discharged from the hospital with an opioid prescription. Most women fill that prescription and 1% continue to use those opioids 90 days after delivery despite no longer requiring them for pain control, predisposing them to opioid dependence. This study aims to determine if transverse abdominis plane (TAP) block using bupivacaine liposome suspension injection (EXPAREL®) significantly reduces the use of opioid medications after discharge in women undergoing scheduled cesarean delivery. The study is a proposed double-blinded, randomized controlled trial. Pregnant women who have completed 37 weeks gestation and are scheduled for cesarean delivery will be randomized to receive a TAP block with 80 ml of mixed liposomal bupivacaine or saline. Based on its use in other surgical settings, the investigators hypothesize that women who receive a liposomal bupivacaine TAP block will use significantly less opioids by postoperative day 7 as calculated in morphine milligram equivalents. In addition to overall consumption of opioids after discharge, other aims to be studied include inpatient opioid use, effect on pain scores, rates of postpartum depression, patient-perceived quality of breastfeeding, patient quality of recovery, and composite adverse outcomes.

With better overall pain control and less dependence on opioids postpartum, liposomal bupivacaine TAP blocks at the time of scheduled cesarean delivery may offer a highly effective analgesic alternative that can help shift the tide in the ongoing opioid epidemic among reproductive females.

• Study Type: Interventional
• Enrollment (Estimated): 97
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Kansas City, Missouri, United States, 64139
      • Truman Medical Center - Lakewood

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Unlabored, scheduled primary or repeat cesarean delivery
• Cesarean performed by obstetrician or surgically-trained family medicine physician
• Ability to complete numeric pain scale assessment and surveys
• Patients who do not speak English but are able to converse via an interpreter both in person and by phone

Exclusion Criteria:

• Complications requiring return to the operating room
• Unscheduled deliveries
• <18 years old, >45 years old
• Twin deliveries
• Preterm deliveries (<37 wks)
• Current or previous history of opioid-substance use disorder according to patient report or medical chart
• Prescription of opioid medication filled in previous 30 days prior to delivery according to patient report, documentation in electronic medical record, or documentation in the prescription drug monitoring program
• Allergy to local anesthetics or NSAIDs
• Cardiovascular disease, eg arrhythmia, or ASA (American Society of Anesthesiologists) Class III or higher
• Diagnosis of liver disorder or dysfunction including fatty liver of pregnancy, preeclampsia with severe features including liver or kidney involvement
• Known significant renal disease, oliguria, or Cr >1.1.
• Platelet count less than or equal to 90k or rapid decline in third trimester or other coagulopathy
• Infection overlying the regional anesthesia site
• Hypovolemia prohibiting regional anesthesia
• General anesthesia

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment; The transversus abdominis plane block is a procedure involving injection of a local anesthetic solution into the abdominal plane between the internal oblique muscle and the transversus abdominis muscle. In our institution, this is done under ultrasound guidance which is the current standard to improve efficacy and limit complications. Liposomal bupivacaine uses an innovative technology consisting of lipid-based particles containing active pharmaceutical agent (bupivacaine) which extends the duration of the medication through a process of gradual release for metabolism.This drug delivery technology extends the duration of action to up to 96 hours when given at a dose of 266 mg liposomal bupivacaine admixed with 30 ml of bupivacaine 0.25% and 30 ml of saline. Forty ml of solution is deposited on the left side of the abdomen and 40 ml on the right.	Drug: Liposomal bupivacaine; Deposition of liposomal bupivacaine; Other Names: EXPAREL; Procedure: TAP block; Transversus abdominis plane block performed to deposit anesthetic
Placebo Comparator: Control; The transversus abdominis plane block will be performed under ultrasound guidance with deposition of 80 ml of saline (40 ml on either side).	Procedure: TAP block; Transversus abdominis plane block performed to deposit anesthetic; Drug: Deposition of saline; Deposition of saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morphine Milligram Equivalents	Amount of opioid medications taken converted to Morphine Milligram Equivalents	7 days after cesarean

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morphine Milligram Equivalents at 48 hours	Total opioid use inpatient at 48 hours as measured in Morphine Milligram Equivalents	Time surgery is complete to 48 hours
Numeric Rating Scale Pain Score on postoperative day 1	Highest documented pain score postoperative day #1 by Numeric Rating Scale Pain level [0-10]. Higher scores denote more pain.	Midnight to midnight postoperative day #1
Time to as needed opioid use	Time to first "as needed" opioid use while inpatient	Inpatient stay up to 6 days
Opioid-spared Percentage	Percentage of patients in each arm that did not receive any additional opioid after surgery	Inpatient stay up to 6 days
Edinburgh Postpartum Depression Scale Score at Discharge	Score on the Edinburgh Postpartum Depression scale [0-30] at discharge. Higher scores denote worse depression. A positive question 10 is also positive.	Inpatient stay up to 6 days
Edinburgh Postpartum Depression Scale Score at 7 days	Score on the Edinburgh Postpartum Depression scale [0-30] by phone interview postoperative day #7. Higher scores denote worse depression. A positive question 10 is also positive.	Postoperative day #7
Edinburgh Postpartum Depression Scale Score at 14 days	Score on the Edinburgh Postpartum Depression scale [0-30] at appointment postoperative day #14. Higher scores denote worse depression. A positive question 10 is also positive.	Postoperative day #14
Edinburgh Postpartum Depression Scale Score at 6 wks	Score on the Edinburgh Postpartum Depression scale [0-30] at 6 week postoperative appointment. Higher scores denote worse depression. A positive question 10 is also positive.	6 weeks postpartum visit
Numeric Rating Scale Pain Score Postoperative day #7	Numeric Rating Scale Pain level [0-10] assessed by phone interview on Postoperative day #7. Higher scores denote more pain.	Postoperative day #7
Numeric Rating Scale Pain Score at Postoperative day #14	Numeric Rating Scale Pain level [0-10] at 2 week post op visit. Higher scores denote more pain.	Postoperative day #14
Numeric Rating Scale Pain Score at 6 wks	Numeric Rating Scale Pain level [0-10] at 6 week post op visit. Higher scores denote more pain.	Postpartum visit 6 wks
Quality of Recovery-15 at discharge	Quality of Recovery scale at discharge	Inpatient stay up to 6 days
Quality of Recovery-15 at 7 day	Quality of Recovery scale at Postoperative day #7 by phone interview [0-150].The Quality of Recovery-15 scores for excellent, good, moderate, and poor recovery were 136-150, 122-135, 90-121, and 0-89, respectively.	Postoperative day #7
Quality of Recovery-15 at Postoperative day #14	Quality of Recovery scale at post op visit [0-150]. The Quality of Recovery-15 scores for excellent, good, moderate, and poor recovery were 136-150, 122-135, 90-121, and 0-89, respectively.	Postoperative day #14
Quality of Recovery-15 at 6 weeks	Quality of Recovery scale at postpartum visit [0-150].The Quality of Recovery-15 scores for excellent, good, moderate, and poor recovery were 136-150, 122-135, 90-121, and 0-89, respectively.	Postpartum visit 6 weeks
Breastfeeding Self-Efficacy Scale Short Form at Postoperative day #7	Breastfeeding Self-Efficacy Scale Short Form at Postoperative day #7 by phone interview [14-70] with higher scores denoting higher confidence	Postoperative day #7
Breastfeeding Self-Efficacy Scale Short Form at Postoperative day #14	Breastfeeding Self-Efficacy Scale Short Form at post op visit [14-70] with higher scores denoting higher confidence	Postoperative day #14
Breastfeeding Self-Efficacy Scale Short Form at 6 weeks	Breastfeeding Self-Efficacy Scale Short Form at postpartum visit [14-70] with higher scores denoting higher confidence	Postpartum 6 weeks
Adverse Events	Adverse outcomes or side effects	Study duration ~ 8 weeks

Collaborators and Investigators

• Sponsor: University of Missouri, Kansas City
• Collaborators: Truman Medical Center
• Investigators: Study Chair: Devika Maulik, MD, Children's Mercy Hospital Kansas City; Study Chair: Gary Sutkin, MD, University of Missouri, Kansas City

Publications and helpful links

General Publications

• Stark PA, Myles PS, Burke JA. Development and psychometric evaluation of a postoperative quality of recovery score: the QoR-15. Anesthesiology. 2013 Jun;118(6):1332-40. doi: 10.1097/ALN.0b013e318289b84b.
• Hebbard P, Fujiwara Y, Shibata Y, Royse C. Ultrasound-guided transversus abdominis plane (TAP) block. Anaesth Intensive Care. 2007 Aug;35(4):616-7. No abstract available.
• Dennis CL. The breastfeeding self-efficacy scale: psychometric assessment of the short form. J Obstet Gynecol Neonatal Nurs. 2003 Nov-Dec;32(6):734-44. doi: 10.1177/0884217503258459.
• Eisenach JC, Pan PH, Smiley R, Lavand'homme P, Landau R, Houle TT. Severity of acute pain after childbirth, but not type of delivery, predicts persistent pain and postpartum depression. Pain. 2008 Nov 15;140(1):87-94. doi: 10.1016/j.pain.2008.07.011. Epub 2008 Sep 24.
• Peahl AF, Dalton VK, Montgomery JR, Lai YL, Hu HM, Waljee JF. Rates of New Persistent Opioid Use After Vaginal or Cesarean Birth Among US Women. JAMA Netw Open. 2019 Jul 3;2(7):e197863. doi: 10.1001/jamanetworkopen.2019.7863. Erratum In: JAMA Netw Open. 2019 Aug 2;2(8):e1911235.
• Martin JA, Hamilton BE, Osterman MJK, Driscoll AK. Births: Final Data for 2018. Natl Vital Stat Rep. 2019 Nov;68(13):1-47.
• Bateman BT, Franklin JM, Bykov K, Avorn J, Shrank WH, Brennan TA, Landon JE, Rathmell JP, Huybrechts KF, Fischer MA, Choudhry NK. Persistent opioid use following cesarean delivery: patterns and predictors among opioid-naive women. Am J Obstet Gynecol. 2016 Sep;215(3):353.e1-353.e18. doi: 10.1016/j.ajog.2016.03.016. Epub 2016 Mar 17.
• Badreldin N, Grobman WA, Chang KT, Yee LM. Opioid prescribing patterns among postpartum women. Am J Obstet Gynecol. 2018 Jul;219(1):103.e1-103.e8. doi: 10.1016/j.ajog.2018.04.003. Epub 2018 Apr 7.
• Tuthill EL, McGrath JM, Graber M, Cusson RM, Young SL. Breastfeeding Self-efficacy: A Critical Review of Available Instruments. J Hum Lact. 2016 Feb;32(1):35-45. doi: 10.1177/0890334415599533. Epub 2015 Aug 28.
• Babazade R, Vadhera RB, Krishnamurthy P, Varma A, Doulatram G, Saade GR, Turan A. Acute postcesarean pain is associated with in-hospital exclusive breastfeeding, length of stay and post-partum depression. J Clin Anesth. 2020 Jun;62:109697. doi: 10.1016/j.jclinane.2019.109697. Epub 2019 Dec 31.
• Mustafa HJ, Wong HL, Al-Kofahi M, Schaefer M, Karanam A, Todd MM. Bupivacaine Pharmacokinetics and Breast Milk Excretion of Liposomal Bupivacaine Administered After Cesarean Birth. Obstet Gynecol. 2020 Jul;136(1):70-76. doi: 10.1097/AOG.0000000000003886.

Helpful Links

• CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: October 29, 2020
• First Submitted That Met QC Criteria: December 19, 2020
• First Posted (Actual): December 22, 2020

Study Record Updates

• Last Update Posted (Estimated): June 13, 2023
• Last Update Submitted That Met QC Criteria: June 12, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: 2026221; 21-018 (Truman Medical Center)

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