Mammoplasty, Postoperative Pain
Conditions
Keywords
Mammoplasty, Postoperative pain, Analgesia
Brief summary
This is a Phase 4, prospective, open-label, non-randomized, sequential study with two treatment groups differing only in the technique used for EXPAREL administration (instillation or infiltration).
Detailed description
Each subject underwent bilateral augmentation mammoplasty and received the same dose of EXPAREL. This primary objective of this study was to assess the efficacy of EXPAREL when administered via infiltration versus instillation as part of bilateral augmentation mammoplasty. The secondary objectives were to further assess other efficacy measures and the safety profile of EXPAREL.
Interventions
DRUGInstillation - EXPAREL
Intravenous (IV) morphine sulfate, hydromorphone, or oral oxycodone with acetaminophen (5/325 mg) will be permitted following surgery, as needed.
DRUGInfiltration - EXPAREL
IV morphine sulfate, hydromorphone, or oral oxycodone with acetaminophen (5/325 mg) will be permitted following surgery, as needed.
Sponsors
Pacira Pharmaceuticals, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Female, 18-75 years of age inclusive. * American Society of Anesthesiologists (ASA) physical status 1-3. * Undergoing bilateral augmentation mammoplasty without any concurrent surgical procedure(s). * Physically and mentally able to participate in the study and complete all study assessments. * Able to give fully informed consent to participate in this study after demonstrating a good understanding of the risks and benefits of the study components.
Exclusion criteria
* History of hypersensitivity or idiosyncratic reactions to amide-type local anesthetics. * Any subject whose anatomy or surgical procedure might, in the opinion of the Investigator, preclude the potential successful local administration of EXPAREL. * Subjects currently pregnant or who may become pregnant during the course of the study. * Any subject who in the opinion of the Investigator might be harmed or be a poor candidate for participation in the study. * Subjects who have received any investigational drug within 30 days prior to study drug administration, or planned administration of another investigational product or procedure during their participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Analgesia | 10 days | The primary outcome measure is the duration of analgesia, measured by the time (hours) from the end surgery to the subject's first postsurgical opioid administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity Assessment Upon Waking in the PACU | Upon waking in the PACO post surgery | Subject-reported pain assessment upon waking in the PACU on a scale of 0 to 10 where 0 = no pain and 10 = worst possible pain. |
| Pain Intensity Assessment at the Time of Hospital Discharge | At the time of hospital discharge | Subject-reported pain assessment at the time of hospital discharge (assessed an average of 3.11 hours after surgery for the Instillation group and 3.20 hours after surgery for the Infiltration group) on a scale from 0 to 10 where 0 = no pain and 10 = worst possible pain. |
| Time to Hospital Discharge Being Written | At the time of hospital discharge | The time (hours) to the hospital discharge being written for subjects in each group, |
| Total Postsurgical Opioid Consumption in the Surgical Center | 10 days | Total amount of opioids (morphine-equivalent mg) administered postsurgically in each group. |
| Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Hospital Discharge | At the time of hospital discharge | Subject-reported satisfaction with postsurgical pain control in the categories of extremely dissatisfied, dissatisfied, neither satisfied nor dissatisfied, satisfied, and extremely satisfied. |
| Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Day 10 | Day 10 after surgery | Subject-reported satisfaction with postsurgical pain control in the categories of extremely dissatisfied, dissatisfied, neither satisfied nor dissatisfied, satisfied, and extremely satisfied. |
| Incidence of Opioid-Related Adverse Events | Through 10 Days Post Surgery | The incidence of adverse events that were assessed as opioid-related |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Infiltration - EXPAREL Group 2 will receive diluted EXPAREL (i.e., the contents of one 20 mL vial, 266 mg, diluted with 20 mL of preservative-free 0.9% normal saline to a total of 40 mL) for postsurgical analgesia. Half of the resulting mixture (i.e., 20 mL) will be administered via local infiltration into each surgical site per the surgeon's normal practice at the beginning of surgery.
Instillation - EXPAREL: Intravenous (IV) morphine sulfate, hydromorphone, or oral oxycodone with acetaminophen (5/325 mg) will be permitted following surgery, as needed. | 9 |
| Instillation - EXPAREL Group 1 will receive diluted EXPAREL (i.e., the contents of one 20 mL vial, 266 mg, diluted with 20 mL of preservative-free 0.9% normal saline to a total of 40 mL) for postsurgical analgesia. Half of the resulting mixture (i.e., 20 mL) will be instilled into each breast pocket at the beginning of surgery.
Infiltration - EXPAREL: IV morphine sulfate, hydromorphone, or oral oxycodone with acetaminophen (5/325 mg) will be permitted following surgery, as needed. | 10 |
| Total | 19 |
Baseline characteristics
| Characteristic | Infiltration - EXPAREL | Total | Instillation - EXPAREL |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 19 Participants | 10 Participants |
| Age, Continuous | 27.8 years STANDARD_DEVIATION 7.25 | 28.8 years STANDARD_DEVIATION 9.57 | 29.7 years STANDARD_DEVIATION 11.41 |
| ASA Classification ASA Class 1 | 5 participants | 14 participants | 9 participants |
| ASA Classification ASA Class 2 | 3 participants | 4 participants | 1 participants |
| Region of Enrollment United States | 9 participants | 19 participants | 10 participants |
| Sex: Female, Male Female | 9 Participants | 19 Participants | 10 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 0 / 10 |
| serious Total, serious adverse events | 0 / 8 | 0 / 10 |
Outcome results
Primary
Duration of Analgesia
The primary outcome measure is the duration of analgesia, measured by the time (hours) from the end surgery to the subject's first postsurgical opioid administration.
Time frame: 10 days
Population: Of the 8 subjects in the Infiltration - EXPAREL group (efficacy analysis set), 5 were censored, leaving 3 subjects who were administered an opioid. Of the 9 subjects in the Instillation - EXPAREL group (efficacy analysis set), 7 were censored, leaving 2 subjects who were administered an opioid.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Infiltration - EXPAREL | Duration of Analgesia | Minimum time to postsurgical opioid | 0.07 hours |
| Infiltration - EXPAREL | Duration of Analgesia | Maximum time to postsurgical opioid | 4.28 hours |
| Instillation - EXPAREL | Duration of Analgesia | Minimum time to postsurgical opioid | 0.3 hours |
| Instillation - EXPAREL | Duration of Analgesia | Maximum time to postsurgical opioid | 4.82 hours |
Secondary
Incidence of Opioid-Related Adverse Events
The incidence of adverse events that were assessed as opioid-related
Time frame: Through 10 Days Post Surgery
Population: There were 8 subjects in the Infiltration - EXPAREL efficacy analysis set and 9 subjects in the Instillation - EXPAREL efficacy analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infiltration - EXPAREL | Incidence of Opioid-Related Adverse Events | 0 participants |
| Instillation - EXPAREL | Incidence of Opioid-Related Adverse Events | 0 participants |
Secondary
Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Day 10
Subject-reported satisfaction with postsurgical pain control in the categories of extremely dissatisfied, dissatisfied, neither satisfied nor dissatisfied, satisfied, and extremely satisfied.
Time frame: Day 10 after surgery
Population: There were 8 subjects in the Infiltration - EXPAREL efficacy analysis set and 9 subjects in the Instillation - EXPAREL efficacy analysis set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Infiltration - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Day 10 | Dissatisfied | 1 participants |
| Infiltration - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Day 10 | Satisfied | 2 participants |
| Infiltration - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Day 10 | Neither Satisfied nor Dissatisfied | 1 participants |
| Infiltration - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Day 10 | Extremely Satisfied | 2 participants |
| Infiltration - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Day 10 | Extremely Dissatisfied | 2 participants |
| Instillation - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Day 10 | Extremely Satisfied | 5 participants |
| Instillation - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Day 10 | Extremely Dissatisfied | 0 participants |
| Instillation - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Day 10 | Dissatisfied | 0 participants |
| Instillation - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Day 10 | Neither Satisfied nor Dissatisfied | 2 participants |
| Instillation - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Day 10 | Satisfied | 2 participants |
Secondary
Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Hospital Discharge
Subject-reported satisfaction with postsurgical pain control in the categories of extremely dissatisfied, dissatisfied, neither satisfied nor dissatisfied, satisfied, and extremely satisfied.
Time frame: At the time of hospital discharge
Population: There were 8 subjects in the Infiltration - EXPAREL efficacy analysis set and 9 subjects in the Instillation - EXPAREL efficacy analysis set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Infiltration - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Hospital Discharge | Dissatisfied | 1 participants |
| Infiltration - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Hospital Discharge | Satisfied | 3 participants |
| Infiltration - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Hospital Discharge | Neither Satisfied nor Dissatisfied | 0 participants |
| Infiltration - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Hospital Discharge | Extremely Satisfied | 3 participants |
| Infiltration - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Hospital Discharge | Extremely Dissatisfied | 1 participants |
| Instillation - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Hospital Discharge | Extremely Satisfied | 4 participants |
| Instillation - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Hospital Discharge | Extremely Dissatisfied | 0 participants |
| Instillation - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Hospital Discharge | Dissatisfied | 0 participants |
| Instillation - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Hospital Discharge | Neither Satisfied nor Dissatisfied | 2 participants |
| Instillation - EXPAREL | Overall Rating of Subject Satisfaction With Postsurgical Pain Control at Hospital Discharge | Satisfied | 3 participants |
Secondary
Pain Intensity Assessment at the Time of Hospital Discharge
Subject-reported pain assessment at the time of hospital discharge (assessed an average of 3.11 hours after surgery for the Instillation group and 3.20 hours after surgery for the Infiltration group) on a scale from 0 to 10 where 0 = no pain and 10 = worst possible pain.
Time frame: At the time of hospital discharge
Population: There were 8 subjects in the Infiltration - EXPAREL efficacy analysis set and 9 subjects in the Instillation - EXPAREL efficacy analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Infiltration - EXPAREL | Pain Intensity Assessment at the Time of Hospital Discharge | 3.8 units on a scale | Standard Deviation 1.39 |
| Instillation - EXPAREL | Pain Intensity Assessment at the Time of Hospital Discharge | 3.4 units on a scale | Standard Deviation 1.88 |
Secondary
Pain Intensity Assessment Upon Waking in the PACU
Subject-reported pain assessment upon waking in the PACU on a scale of 0 to 10 where 0 = no pain and 10 = worst possible pain.
Time frame: Upon waking in the PACO post surgery
Population: There were 9 subjects in the Infiltration - EXPAREL efficacy analysis set and 8 subjects in the Instillation - EXPAREL efficacy analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Infiltration - EXPAREL | Pain Intensity Assessment Upon Waking in the PACU | 4.5 units on a scale | Standard Deviation 2.98 |
| Instillation - EXPAREL | Pain Intensity Assessment Upon Waking in the PACU | 3.7 units on a scale | Standard Deviation 2.6 |
Secondary
Time to Hospital Discharge Being Written
The time (hours) to the hospital discharge being written for subjects in each group,
Time frame: At the time of hospital discharge
Population: There were 8 subjects in the Infiltration - EXPAREL efficacy analysis set and 9 subjects in the Instillation - EXPAREL efficacy analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Infiltration - EXPAREL | Time to Hospital Discharge Being Written | 3.2 hours | Standard Deviation 0.941 |
| Instillation - EXPAREL | Time to Hospital Discharge Being Written | 3.11 hours | Standard Deviation 1.005 |
Secondary
Total Postsurgical Opioid Consumption in the Surgical Center
Total amount of opioids (morphine-equivalent mg) administered postsurgically in each group.
Time frame: 10 days
Population: There were 8 subjects in the Infiltration - EXPAREL efficacy analysis set and 9 subjects in the Instillation - EXPAREL efficacy analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Infiltration - EXPAREL | Total Postsurgical Opioid Consumption in the Surgical Center | 4.5 mg | Standard Deviation 6.26 |
| Instillation - EXPAREL | Total Postsurgical Opioid Consumption in the Surgical Center | 3.0 mg | Standard Deviation 7.74 |