Pain
Conditions
Brief summary
The purpose of this prospective, blinded assessor, randomized trial is to assess opioid use and patient-reported outcomes of EXPAREL as a foundation in postsurgical pain therapy in Transversus Abdominis Plane (TAP) infiltration in lower abdominal surgical procedures.
Detailed description
The purpose of this prospective, blinded assessor, randomized trial is to assess opioid use and patient-reported outcomes of EXPAREL as a foundation in postsurgical pain therapy in Transversus Abdominis Plane (TAP) infiltration in lower abdominal surgical procedures; primary endpoint signal seen during pre-specified interim analysis.
Interventions
DRUGEXPAREL
TAP with EXPAREL
DRUGPlacebo
Placebo
Sponsors
Pacira Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and females \>18 years of age * American Society of Anesthesiologists (ASA) physical status 1-3 * Undergoing either lower abdominal surgery defined as Laparoscopic Hysterectomy (female), Laparoscopic Myomectomy (female), Laparoscopic Colectomy (male/female) * Physically and mentally able to give full informed consent to participate in this study and complete all study assessments within the timeframes required (including electronic diaries should patient be discharged prior to day 4) * Capable of returning the diary after POD 4 by mail (preferably) or upon follow up visit.
Exclusion criteria
* History of hypersensitivity or idiosyncratic reactions to amide-type local anesthetics. * Any patient whose anatomy, or surgical procedure, in the opinion of the Investigator, might preclude the potential successful local administration of EXPAREL. * Patients who have received any investigational drug within 30 days prior to EXPAREL administration, or planned administration of another investigational product or procedure during their participation in this study. * Any chronic condition requiring use of opioids for treatment of a medical condition for 2 weeks or more prior to surgery. * Confirmed pregnancy at time of enrollment or breast feeding (females of child-bearing potential). * Patients that would constitute a contraindication to participation in the study, or cause inability to comply with the study requirements. * Any patient with diagnosed or potential metastatic disease. * Any condition that in the investigator's opinion might be harmed or be a poor candidate for participation in the study (such as patients requiring long acting opioids as part of the induction medications). * Initiation of treatment with any of the following medications within 1 month of study drug administration or if the medication(s) are being given to control pain: selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), gabapentin, pregabalin (Lyrica®), or duloxetine (Cymbalta®) * History of suspected or known addiction to, or abuse of, illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Opioid Consumption Post Surgery (Cumulative Total) Until Discharge Readiness or Post Surgery Day 4 | From surgery through 4 days postsurgery | Total Opioid Consumption Post Surgery (cumulative total) Until Discharge Readiness or Post Surgery Day 4 |
| Overall Benefit of Analgesic Score (OBAS) at Day 3 | Postsurgical day 1 through day 3 | Severity of postsurgical pain, satisfaction with pain management, and impact of opioid-related symptom distress measured using the Overall Benefit of Analgesic Score (OBAS) - primary endpoint is mean difference in OBAS at Day 3. (0=minimal pain and 4=maximum imaginable pain) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Extent and Degree of Anesthetic Blockade | Prior to TAP, immediately postoperatively, and daily through discharge or Day 4 | Extent and degree of anesthetic blockage measured using a 5-point sensation scale. |
| Severity of Postsurgical Pain | Immediately in PACU postsurgery and prior to pain medication until discharge (or Day 4) | Severity of postsurgical pain measured using an 11-point numerical rating scale (NRS 0-10). |
| Quality of Recovery | Daily through Post Op Day 4 | Measured using the Quality of Recovery 15 questionnaire (QoR-15) |
| Frequency of Patient Calls Post-discharge | Post-discharge through 4 days postsurgery | Frequency of patient calls post-discharge related to pain and unscheduled hospital/surgeon visits |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EXPAREL EXPAREL (266 mg/20 mL) with 40 mL of 0.9% normal saline for a total volume of 60 mL, 30 mL to be administered to the right TAP and 30 mL to be administered to the left TAP.
EXPAREL | 33 |
| Placebo The placebo control was established using a grade-2 sham; no infiltration occurred.
Placebo | 34 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Intra-op findings, etc. | 3 | 0 |
Baseline characteristics
| Characteristic | EXPAREL | Placebo | Total |
|---|---|---|---|
| Age, Customized Over 75 | 1 participants | 1 participants | 2 participants |
| Age, Customized Under 75 | 32 participants | 33 participants | 65 participants |
| Region of Enrollment United States | 33 participants | 34 participants | 67 participants |
| Sex: Female, Male Female | 27 Participants | 28 Participants | 55 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 33 | 0 / 34 |
| serious Total, serious adverse events | 1 / 33 | 1 / 34 |
Outcome results
Primary
Overall Benefit of Analgesic Score (OBAS) at Day 3
Severity of postsurgical pain, satisfaction with pain management, and impact of opioid-related symptom distress measured using the Overall Benefit of Analgesic Score (OBAS) - primary endpoint is mean difference in OBAS at Day 3. (0=minimal pain and 4=maximum imaginable pain)
Time frame: Postsurgical day 1 through day 3
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| EXPAREL | Overall Benefit of Analgesic Score (OBAS) at Day 3 | 3.05 units on a scale | Standard Error 0.56 |
| Placebo | Overall Benefit of Analgesic Score (OBAS) at Day 3 | 4.63 units on a scale | Standard Error 0.56 |
p-value: 0.0456Mixed Models Analysis
Primary
Total Opioid Consumption Post Surgery (Cumulative Total) Until Discharge Readiness or Post Surgery Day 4
Total Opioid Consumption Post Surgery (cumulative total) Until Discharge Readiness or Post Surgery Day 4
Time frame: From surgery through 4 days postsurgery
| Arm | Measure | Value (MEAN) |
|---|---|---|
| EXPAREL | Total Opioid Consumption Post Surgery (Cumulative Total) Until Discharge Readiness or Post Surgery Day 4 | 3.79 Opioid consumption (mg) |
| Placebo | Total Opioid Consumption Post Surgery (Cumulative Total) Until Discharge Readiness or Post Surgery Day 4 | 3.72 Opioid consumption (mg) |
p-value: >0.8ANCOVA
Secondary
Extent and Degree of Anesthetic Blockade
Extent and degree of anesthetic blockage measured using a 5-point sensation scale.
Time frame: Prior to TAP, immediately postoperatively, and daily through discharge or Day 4
Population: The analysis was not conducted due to the early termination of this study.
Secondary
Frequency of Patient Calls Post-discharge
Frequency of patient calls post-discharge related to pain and unscheduled hospital/surgeon visits
Time frame: Post-discharge through 4 days postsurgery
Population: The analysis was not conducted due to the early termination of this study.
Secondary
Quality of Recovery
Measured using the Quality of Recovery 15 questionnaire (QoR-15)
Time frame: Daily through Post Op Day 4
Population: The analysis was not conducted due to the early termination of this study.
Secondary
Severity of Postsurgical Pain
Severity of postsurgical pain measured using an 11-point numerical rating scale (NRS 0-10).
Time frame: Immediately in PACU postsurgery and prior to pain medication until discharge (or Day 4)
Population: The analysis was not conducted due to the early termination of this study.