Liposomal Bupivacaine at Cesarean Delivery to Decrease Post-operative Pain

This is a randomized controlled trial to test whether the use of liposomal bupivacaine at the time of cesarean delivery may decrease post-operative pain scores.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative
• Intervention / Treatment: Drug: Placebo; Drug: Liposomal bupivacaine

Detailed Description

This study is a randomized controlled trial. A total of 80 patients will be randomized 1:1 to intervention (liposomal bupivacaine) versus control (placebo solution).

The planned intervention is the infiltration of liposomal bupivacaine (or control) at the time of fascial closure at a Pfannenstiel incision, after the delivery of the infant and repair of the hysterotomy. The procedure to instill the drug is as follows: Once the patient is in the operating room, neuraxial anesthesia will be administered per routine practice. A Pfannenstiel skin incision will be made. The usual cesarean delivery procedure will be performed at the discretion of the surgeon. Once the surgical team is about to begin fascial closure, the study drug will then be infiltrated by a member of the study team, with 50% of the study solution in subcutaneous space and 50% in the fascial plane, taking care to evenly spread the drug in the superior and inferior aspects of the incision. For the fascial infiltration, liposomal bupivacaine will be preferentially infiltrated laterally. The remainder of the cesarean delivery will proceed according to the usual fashion. At any point in the cesarean delivery, the surgeon may chose to administer or withhold ketorolac.

Post-operative pain management will be: intrathecal morphine, scheduled ketorolac 30mg IV x 24h followed by ibuprofen 600mg q6h x 24h, scheduled Tylenol 650mg q6h x 48h, and prn oxycodone 5-10mg q4h. This is the current pain management protocol for postoperative women after cesarean delivery. If Tylenol or NSAIDs are contraindicated, either due to the discretion of the clinical team or pre-existing patient contraindication, these will not be administered but are not a reason for study exclusion.

The investigators plan to enroll 80 patients into this pilot study, 40 per group. This sample size is based on prior data among women who had a cesarean delivery at this institution, and were asked to report their pain scores with activity at 48- and 72- hours after operation. With this sample size, the investigators have 80% power to detect a 1.5 point difference in pain at 48 hours, and 90% power to detect a 1.5 point difference in pain at 72 hours, and account for any protocol violations or loss to follow-up.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Scheduled cesarean delivery via Pfannenstiel incision;
2. Planned neuraxial anesthetic with intrathecal morphine and fentanyl administration.

Exclusion Criteria:

1. Current or prior use of methadone, buprenorphine, or other opioids before cesarean delivery;
2. Contraindication to neuraxial anesthetic;
3. Allergy to local anesthetic;
4. Planned general anesthetic.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Normal saline will be infiltrated	Drug: Placebo; placebo injection in the Pfannenstiel incision
Active Comparator: Intervention; Liposomal bupivacaine will be infiltrated	Drug: Liposomal bupivacaine; liposomal bupivacaine injection in the Pfannenstiel incision; Other Names: Exparel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Score With Activity	Pain score with activity. PAIN OUT scale, which is a 0-10 scale, where 10 is more pain. 2 patients in the liposomal bupivacaine group were discharged prior to 48 hour assessment, therefore denominator for this outcome is 37, not 39	at 48-hours post-operatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Score With Activity	Pain score with activity. PAIN OUT scale, which is a 0-10 scale, where 10 is more pain. 4 patients in the placebo group and 7 patients in the liposomal bupivacaine group were discharged prior to the 72 hour assessment	at 72 -hours post-operatively
Total Opioid Use (in Morphine Equivalents)	Total opioid use (in morphine equivalents)	72-hours post-operatively
Satisfaction With Post-operative Pain Control	PAIN OUT Tool, 0-10 scale, where 0 is not satisfied and 10 is satisfied	48-hours post-operatively
Postoperative Hospital Length of Stay	Postoperative hospital length of stay	0 to 96 hours postoperatively
Number of Patients With Wound Complication - Separation, Dehiscence, Infection	Wound complication - separation, dehiscence, infection	14 days postoperatively
Number of Patients With Allergic Reaction Attributable to Local Anesthestic	incisional rash, hives, anaphylaxis	0-96 hours postoperatively
Operative Time of Cesarean Delivery	Operative time of cesarean delivery	Intraoperative time measurement, from skin incision to skin closure. Measured within 24h of admission.
Patient Satisfaction With Pain Management at 6w Postpartum	Phone follow up to ascertain satisfaction with pain control, Likert 5 point scale used	6 weeks postpartum

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: William H Barth, Jr, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Prabhu M, Clapp MA, McQuaid-Hanson E, Ona S, O'Donnell T, James K, Bateman BT, Wylie BJ, Barth WH Jr. Liposomal Bupivacaine Block at the Time of Cesarean Delivery to Decrease Postoperative Pain: A Randomized Controlled Trial. Obstet Gynecol. 2018 Jul;132(1):70-78. doi: 10.1097/AOG.0000000000002649.

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2017
• Primary Completion (Actual): September 25, 2017
• Study Completion (Actual): November 3, 2017

Study Registration Dates

• First Submitted: November 4, 2016
• First Submitted That Met QC Criteria: November 7, 2016
• First Posted (Estimate): November 9, 2016

Study Record Updates

• Last Update Posted (Actual): August 27, 2018
• Last Update Submitted That Met QC Criteria: August 22, 2018
• Last Verified: May 1, 2018

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: 2016P002307/MGH

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