Elective Cesarean Section, Pain Management
Conditions
Keywords
bupivacaine, EXPAREL, analgesic, TAP Block, C-Section, Cesarean Section, elective c-section, TAP
Brief summary
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
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.
Interventions
DRUG50 mcg Duramorph+ EXPAREL + multi-modal pain regimen
Intrathecal injection of 50 mcg Duramorph + EXPAREL administered via TAP infiltration + multi-modal pain regimen.
DRUG150 mcg Duramorph + multi-modal pain regimen
Intrathecal injection of 150 mcg Duramorph + multi-modal pain regimen.
DRUGExparel TAP + multi-modal pain regimen
EXPAREL administered via TAP infiltration + multi-modal pain regimen.
Sponsors
Pacira Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Females 18 years of age and older at screening. 2. Term pregnancies of 37 to 42 weeks gestation, scheduled to undergo elective C-section. 3. American Society of Anesthesiology (ASA) physical status 1, 2, or 3. 4. Able to provide informed consent, adhere to the study visit schedule, and complete all study assessments.
Exclusion criteria
1. Subjects who, in the opinion of the study site principal investigator, have a high-risk pregnancy. 2. Subjects with a pregnancy-induced medical condition or complication. 3. Subjects with 3 or more prior C-sections. 4. Pre-pregnancy body mass index \>50 kg/m2. 5. Allergy, hypersensitivity, intolerance, or contraindication to any of the study medications. 6. Planned concurrent surgical procedure with the exception of salpingo-oophorectomy or tubal ligation. 7. Severely impaired renal or hepatic function. 8. Subjects at an increased risk for bleeding or a coagulation disorder. 9. Concurrent painful physical condition that may require analgesic treatment in the postsurgical period for pain that is not strictly related to the surgery. 10. 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. 11. History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years. 12. Administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug. 13. Previous participation in an EXPAREL study. 14. Any clinically significant event or condition uncovered during the surgery that might render the subject medically unstable or complicate the subject's postsurgical course. 15. Receives the epidural component of combined spinal epidural (CSE) anesthesia during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Postsurgical Opioid Consumption Through 72 Hours | Through 72 hours post-surgery | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Opioid-free Subjects | through 72 hours or hospital discharge, whichever came first | Percentage of opioid-free subjects. LS Means probability from the logistic regression with treatment, site, age, and height as explanatory variables. |
| Severity of Itching (Numeric Rating Scale Score) | through 72 hours after surgery | Severity of itching (Numeric Rating Scale score from 0(being none)-10(being the worst)) |
| Opioid Related Symptom Distress Scale Score (ORSDS) | through 72 hours after surgery | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 (Standard of Care Group) 150 mcg Duramorph® + postoperative multi-modal pain regimen. No EXPAREL TAP infiltration
150 mcg Duramorph + multi-modal pain regimen: Intrathecal injection of 150 mcg Duramorph + multi-modal pain regimen. | 53 |
| Group 2 (Duramorph + EXPAREL TAP) 50 mcg Duramorph + EXPAREL TAP infiltration + postoperative multi-modal pain regimen.
50 mcg Duramorph+ EXPAREL + multi-modal pain regimen: Intrathecal injection of 50 mcg Duramorph + EXPAREL administered via TAP infiltration + multi-modal pain regimen. | 48 |
| Group 3 (EXPAREL TAP) EXPAREL TAP infiltration + postoperative multi-modal pain regimen. No Duramorph.
Exparel TAP + multi-modal pain regimen: EXPAREL administered via TAP infiltration + multi-modal pain regimen. | 52 |
| Total | 153 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Delivered early | 0 | 1 | 0 |
| Overall Study | difficult surgery | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | not suitable to proceed | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 3 | 5 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Group 2 (Duramorph + EXPAREL TAP) | Total | Group 1 (Standard of Care Group) | Group 3 (EXPAREL TAP) |
|---|---|---|---|---|
| Age, Continuous | 34.1 years STANDARD_DEVIATION 4.93 | 33.3 years STANDARD_DEVIATION 4.88 | 33.2 years STANDARD_DEVIATION 4.67 | 32.7 years STANDARD_DEVIATION 5.03 |
| American Society of Anesthesiologists (ASA) Physical Status Classification ASA I | 0 Participants | 5 Participants | 2 Participants | 3 Participants |
| American Society of Anesthesiologists (ASA) Physical Status Classification ASA II | 45 Participants | 131 Participants | 47 Participants | 39 Participants |
| American Society of Anesthesiologists (ASA) Physical Status Classification ASA III | 3 Participants | 17 Participants | 4 Participants | 10 Participants |
| Body Mass Index (pre-pregnancy) | 31.08 kg/m^2 STANDARD_DEVIATION 5.181 | 31.68 kg/m^2 STANDARD_DEVIATION 5.49 | 31.69 kg/m^2 STANDARD_DEVIATION 5.091 | 32.23 kg/m^2 STANDARD_DEVIATION 6.179 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 18 Participants | 6 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 134 Participants | 46 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 16 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 15 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 9 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 36 Participants | 111 Participants | 41 Participants | 34 Participants |
| Region of Enrollment United States | 48 participants | 153 participants | 53 participants | 52 participants |
| Sex: Female, Male Female | 48 Participants | 153 Participants | 53 Participants | 52 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 48 | 0 / 52 |
| other Total, other adverse events | 43 / 53 | 41 / 48 | 30 / 52 |
| serious Total, serious adverse events | 2 / 53 | 2 / 48 | 2 / 52 |
Outcome results
Primary
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
Time frame: Through 72 hours post-surgery
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 (Standard of Care Group) | Total Postsurgical Opioid Consumption Through 72 Hours | 69.3 OMED mg | Standard Error 1.15 |
| Group 2 (Duramorph + EXPAREL TAP) | Total Postsurgical Opioid Consumption Through 72 Hours | 36.1 OMED mg | Standard Error 1.16 |
| Group 3 (EXPAREL TAP) | Total Postsurgical Opioid Consumption Through 72 Hours | 22.1 OMED mg | Standard Error 1.16 |
Secondary
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.
Time frame: through 72 hours after surgery
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 (Standard of Care Group) | Opioid Related Symptom Distress Scale Score (ORSDS) | 0.33 score on a scale | Standard Error 0.055 |
| Group 2 (Duramorph + EXPAREL TAP) | Opioid Related Symptom Distress Scale Score (ORSDS) | 0.23 score on a scale | Standard Error 0.053 |
| Group 3 (EXPAREL TAP) | Opioid Related Symptom Distress Scale Score (ORSDS) | 0.35 score on a scale | Standard Error 0.051 |
Secondary
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.
Time frame: through 72 hours or hospital discharge, whichever came first
Population: LS Means probability from the logistic regression with treatment, site, age, and height as explanatory variables.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (Standard of Care Group) | Percentage of Opioid-free Subjects | 22.4 percentage of participants, opioid free |
| Group 2 (Duramorph + EXPAREL TAP) | Percentage of Opioid-free Subjects | 28.8 percentage of participants, opioid free |
| Group 3 (EXPAREL TAP) | Percentage of Opioid-free Subjects | 30 percentage of participants, opioid free |
Secondary
Severity of Itching (Numeric Rating Scale Score)
Severity of itching (Numeric Rating Scale score from 0(being none)-10(being the worst))
Time frame: through 72 hours after surgery
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 (Standard of Care Group) | Severity of Itching (Numeric Rating Scale Score) | 1.48 score on a scale | Standard Error 0.161 |
| Group 2 (Duramorph + EXPAREL TAP) | Severity of Itching (Numeric Rating Scale Score) | 0.94 score on a scale | Standard Error 0.176 |
| Group 3 (EXPAREL TAP) | Severity of Itching (Numeric Rating Scale Score) | 0.61 score on a scale | Standard Error 0.167 |