Efficacy and Safety of EXPAREL Versus Standard of Care (SoC) in Subjects Undergoing Elective Cesarean Section

Study Overview
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Brief Summary
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The purpose of this study is to compare total opioid consumption by subjects in different treatment groups. Another purpose of this study is to assess how well EXPAREL works, collect any safety data and assess your satisfaction using EXPAREL.

Detailed Description
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This is a Phase-4, multicenter, randomized, active-controlled study in approximately 182 adult women undergoing elective C-section. All subjects will remain in the hospital for up to 72 hours post surgery. Subjects will be screened within 30 days prior to surgery. During the screening visit, subjects will be assessed for any past or present medical conditions that in the opinion of the investigator would preclude them from study participation. After the Informed Consent Form (ICF) is signed, a medical history, surgical history, physical examination, 12-lead electrocardiogram (ECG), vital sign measurements, alcohol breath test and urine drug screen, and clinical laboratory tests (hematology and chemistry) will be performed. On Day 1, prior to the C-section, eligible subjects will be randomized in a 1:1:1 ratio into one of the three treatment groups listed below: Group 1: 150 mcg Duramorph® (SOC arm)+ postoperative multi-modal pain regimen as defined in this protocol. No EXPAREL TAP infiltration following skin-incision closure. Group 2: 50 mcg Duramorph + EXPAREL TAP infiltration following skin-incision closure + postoperative multi-modal pain regimen as defined in this protocol. Group 3: EXPAREL TAP infiltration following skin-incision closure + postoperative multi-modal pain regimen as defined in this protocol. No Duramorph. Rescue Medication will be provided, as needed, for all subjects. Subjects will remain in the hospital for up to 72 hours after surgery. Total opioid burden and Pain intensity scores using a 10 cm Visual Analog Scale (VAS) will be collected. Daily pain intensity score (VAS) and all pain medications will be collected through Day 14. A phone call will be made to each subject on Day 14 and Day 30.

Official Title
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A Multicenter, Randomized, Active-Controlled Study to Evaluate the Efficacy and Safety of EXPAREL When Administered Via Infiltration Into the Transversus Abdominis Plane Versus Standard of Care in Subjects Undergoing Elective Cesarean Section (CHOICE)

Conditions
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Elective Cesarean Section, Pain Management

Intervention / Treatment
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* Drug: 50 mcg Duramorph+ EXPAREL + multi-modal pain regimen
* Drug: 150 mcg Duramorph + multi-modal pain regimen
* Drug: Exparel TAP + multi-modal pain regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females 18 years of age and older at screening. Term pregnancies of 37 to 42 weeks gestation, scheduled to undergo elective C-section. American Society of Anesthesiology (ASA) physical status 1, 2, or 3. Able to provide informed consent, adhere to the study visit schedule, and complete all study assessments. Exclusion Criteria: Subjects who, in the opinion of the study site principal investigator, have a high-risk pregnancy. Subjects with a pregnancy-induced medical condition or complication. Subjects with 3 or more prior C-sections. Pre-pregnancy body mass index >50 kg/m2. Allergy, hypersensitivity, intolerance, or contraindication to any of the study medications. Planned concurrent surgical procedure with the exception of salpingo-oophorectomy or tubal ligation. Severely impaired renal or hepatic function. Subjects at an increased risk for bleeding or a coagulation disorder. Concurrent painful physical condition that may require analgesic treatment in the postsurgical period for pain that is not strictly related to the surgery. Clinically significant medical disease in either the mother or baby that, in the opinion of the investigator, would make participation in a clinical study inappropriate. History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years. Administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug. Previous participation in an EXPAREL study. Any clinically significant event or condition uncovered during the surgery that might render the subject medically unstable or complicate the subject's postsurgical course. Receives the epidural component of combined spinal epidural (CSE) anesthesia during the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1 (Standard of Care Group)<br>150 mcg Duramorph® + postoperative multi-modal pain regimen. No EXPAREL TAP infiltration | Drug: 150 mcg Duramorph + multi-modal pain regimen<br>* Intrathecal injection of 150 mcg Duramorph + multi-modal pain regimen.<br>|
| Experimental: Group 2 (Duramorph + EXPAREL TAP)<br>50 mcg Duramorph + EXPAREL TAP infiltration + postoperative multi-modal pain regimen. | Drug: 50 mcg Duramorph+ EXPAREL + multi-modal pain regimen<br>* Intrathecal injection of 50 mcg Duramorph + EXPAREL administered via TAP infiltration + multi-modal pain regimen.<br>|
| Experimental: Group 3 (EXPAREL TAP)<br>EXPAREL TAP infiltration + postoperative multi-modal pain regimen. No Duramorph. | Drug: Exparel TAP + multi-modal pain regimen<br>* EXPAREL administered via TAP infiltration + multi-modal pain regimen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Postsurgical Opioid Consumption Through 72 Hours | To Compare total opioid consumption through 72 hours following EXPAREL infiltration into the Transversus abdominus plane (TAP) with SOC in subjects undergoing an elective C-section | Through 72 hours post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Opioid-free Subjects | Percentage of opioid-free subjects. LS Means probability from the logistic regression with treatment, site, age, and height as explanatory variables. | through 72 hours or hospital discharge, whichever came first | 
| Severity of Itching (Numeric Rating Scale Score) | Severity of itching (Numeric Rating Scale score from 0(being none)-10(being the worst)) | through 72 hours after surgery | 
| Opioid Related Symptom Distress Scale Score (ORSDS) | The Opioid-Related Symptom Distress Scale (ORSDS) is a 4-point scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness) for 10 symptoms. The symptom-specific ORSDS is the average of the 3 symptom distress dimensions. The composite ORSDS is the average of 10 symptom-specific scores. Each question will receive a score from 0-4 the composite score for each subject is the average of all scores. A higher score indicates a worse outcome. | through 72 hours after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bupivacaine, EXPAREL, analgesic, TAP Block, C-Section, Cesarean Section, elective c-section, TAP