Bowel Obstruction
Conditions
Keywords
laparoscopic colectomy
Brief summary
This study is designed to compare the standard of care against EXPAREL (bupivacaine liposome injectable suspension) to determine if total opioid consumption is reduced when using EXPAREL, therefore possibly reducing total hospital costs.
Detailed description
This is a Phase 4, prospective, sequential, open-label study designed to evaluate the efficacy, safety, and health economic benefits of intraoperative local wound infiltration with EXPAREL (bupivacaine liposome injectable suspension) compared with postsurgical administration of standardized intravenous (IV) morphine sulfate or Sponsor-approved equivalent for postsurgical analgesia in adult patients undergoing laparoscopic colectomy with general anesthesia.
Interventions
Patients in this group will receive IV morphine sulfate or Sponsor-approved equivalent via a patient-controlled analgesia (PCA) pump, as needed. The PCA pump will be set up postsurgically as soon as possible and prior to the patient leaving the post-anesthesia care unit (PACU) or immediately upon transfer to a floor if the stay in the PACU is less than one hour.
DRUGEXPAREL
Patients will receive 266 mg EXPAREL diluted with preservative-free 0.9% normal saline to a total volume of 40 cc administered via wound infiltration prior to wound closure. When not contraindicated, 30 mg IV ketorolac will be given at the end of surgery. If not indicated, an IV non-steroidal anti-inflammatory drug (NSAID) may be substituted per the site's standard of care. All patients will be offered rescue analgesia, as needed.
Sponsors
Registrat-Mapi
Pacira Pharmaceuticals, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female, at least 18 years of age. * Patients scheduled to undergo laparoscopic segmental colectomy with planned primary anastamosis, as defined by cecectomy, right hemicolectomy, resection of transverse colon, left hemicolectomy, or sigmoidectomy. (Note: patients who converted from a planned laparoscopic colectomy to an open colectomy were not eligible.) * Ability to provide informed consent, adhere to study visit schedule, and complete all study assessments.
Exclusion criteria
* Patients with a history of hypersensitivity or idiosyncratic reactions or intolerance to any local anesthetic, opioid, or propofol. * Patients who abuse alcohol or other drug substance. * Patients with severe hepatic impairment. * Patients currently pregnant or who may become pregnant during the course of the study or who are unwilling to use acceptable means of contraception for at least 1 month before and 1 month after dosing. Acceptable means of contraception include hormonal contraceptives (e.g., oral, injectable, implantable), effective barrier methods (e.g., condoms with spermicide), intrauterine device, lifestyle with a personal choice of abstinence, non-heterosexual lifestyle, or in a strictly monogamous relationship with a partner who has had a vasectomy. * Patients with any psychiatric, psychological, or other condition that the Investigator feels may make the patient an inappropriate candidate for this clinical study. * Participation in an EXPAREL study within the last 30 days. * Patients who have received any investigational drug within 30 days prior to study drug administration, or planned administration of another investigational product or procedure during the patient's participation in this study. In addition, a patient was ineligible if he or she met the following criteria during surgery: * Patients who had any concurrent surgical procedure. * Patients with unplanned multiple segmental resections of large intestine. * Patients who converted from laparoscopic-assisted colectomy to traditional open colectomy. * Patients who had unplanned, temporary or permanent colostomies, ileostomies, or the like placed. * Patients who received intraoperative administration of opioids (other than fentanyl or analogs) or any other analgesic, local anesthetics, or anti-inflammatory agents. * Patients who received Entereg.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Opioid Burden | Wound closure to time hospital discharge order is written or Day 30, whichever is sooner. | Total opioid consumed (IV and PO) postsurgically until hospital discharge order is written or through Day 30, whichever is sooner. |
| Health Economic Benefits - Total Cost of Hospitalization | Wound closure to time hospital discharge order is written or Day 30, whichever is sooner. | Total cost of hospitalization until the time hospital discharge order is written or through Day 30, whichever was sooner. |
| Health Economic Benefits - Length of Stay (LOS) | Wound closure at time hospital discharge order is written or Day 30, whichever is sooner | Length of stay, recorded in days, defined as the time of completion of the wound closure until the hospital discharge order is written or through Day 30, whichever is sooner. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Opioid-related Adverse Events | Wound closure at time hospital discharge order is written or Day 30, whichever is sooner. | Incidence of opioid-related adverse events defined as somnolence, respiratory depression, hypoventilation, hypoxia, dry mouth, nausea, vomiting, constipation, sedation, confusion, pruritus, urinary retention, and postoperative ileus. |
| Patient Satisfaction With Pain Treatment After Surgery | Wound closure at time hospital discharge order is written or Day 30, whichever is sooner. | Responses to question pertaining to patient satisfaction with pain treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IV Morphine Sulfate or Sponsor-approved Equivalent Standard of Care (SOC)
IV morphine sulfate or Sponsor-approved equivalent: Patients in this group received IV morphine sulfate or Sponsor-approved equivalent via a patient-controlled analgesia (PCA) pump, as needed. The PCA pump was set up postsurgically as soon as possible and prior to the patient leaving the post-anesthesia care unit (PACU) or immediately upon transfer to a floor if the stay in the PACU was less than one hour. | 67 |
| EXPAREL EXPAREL (bupivacaine liposome injectable suspension)
EXPAREL: Patients received 266 mg EXPAREL diluted with preservative-free 0.9% normal saline to a total volume of 40 cc administered via wound infiltration prior to wound closure. When not contraindicated, 30 mg IV ketorolac was given at the end of surgery. If not indicated, an IV non-steroidal anti-inflammatory drug (NSAID) could be substituted per the site's standard of care.
All patients were offered rescue analgesia, as needed. | 38 |
| Total | 105 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Didn't meet intraoperative criteria | 8 | 7 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 2 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | IV Morphine Sulfate or Sponsor-approved Equivalent | EXPAREL | Total |
|---|---|---|---|
| Age, Continuous | 58.6 years STANDARD_DEVIATION 14.35 | 57.8 years STANDARD_DEVIATION 11.86 | 58.3 years STANDARD_DEVIATION 13.45 |
| American Society of Anesthesiologist (ASA) Classification Mild Systemic Disease [2] | 32 participants | 25 participants | 57 participants |
| American Society of Anesthesiologist (ASA) Classification Normal [1] | 1 participants | 0 participants | 1 participants |
| American Society of Anesthesiologist (ASA) Classification Severe Systemic Disease [3] | 32 participants | 13 participants | 45 participants |
| American Society of Anesthesiologist (ASA) Classification Severe Systemic Disease Threat to Life [4] | 2 participants | 0 participants | 2 participants |
| Patient's Pain Level 24 Hours Prior to Surgery | 1.9 units on a scale STANDARD_DEVIATION 2.14 | 1.3 units on a scale STANDARD_DEVIATION 0.86 | 1.7 units on a scale STANDARD_DEVIATION 1.81 |
| Race/Ethnicity, Customized Hispanic or Latino | 7 participants | 4 participants | 11 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 60 participants | 34 participants | 94 participants |
| Sex: Female, Male Female | 35 Participants | 21 Participants | 56 Participants |
| Sex: Female, Male Male | 32 Participants | 17 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 53 / 67 | 15 / 38 |
| serious Total, serious adverse events | 9 / 67 | 5 / 38 |
Outcome results
Primary
Health Economic Benefits - Length of Stay (LOS)
Length of stay, recorded in days, defined as the time of completion of the wound closure until the hospital discharge order is written or through Day 30, whichever is sooner.
Time frame: Wound closure at time hospital discharge order is written or Day 30, whichever is sooner
Population: Of the 77 subjects who were enrolled in Group 1, 56 were included in the efficacy analysis set. Of the 45 subjects who were enrolled in Group 2, 26 were included in the efficacy analysis set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IV Morphine Sulfate or Sponsor-approved Equivalent | Health Economic Benefits - Length of Stay (LOS) | 4.0 days |
| EXPAREL | Health Economic Benefits - Length of Stay (LOS) | 3.0 days |
p-value: 0.0019Log Rank
Primary
Health Economic Benefits - Total Cost of Hospitalization
Total cost of hospitalization until the time hospital discharge order is written or through Day 30, whichever was sooner.
Time frame: Wound closure to time hospital discharge order is written or Day 30, whichever is sooner.
Population: Of the 77 subjects who were enrolled in Group 1, 56 were included in the efficacy analysis set. Of the 45 subjects who were enrolled in Group 2, 26 were included in the efficacy analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Morphine Sulfate or Sponsor-approved Equivalent | Health Economic Benefits - Total Cost of Hospitalization | 15158.79 dollars | Standard Deviation 11417.5 |
| EXPAREL | Health Economic Benefits - Total Cost of Hospitalization | 14802.70 dollars | Standard Deviation 18382.12 |
p-value: 0.2612ANOVA
Primary
Total Opioid Burden
Total opioid consumed (IV and PO) postsurgically until hospital discharge order is written or through Day 30, whichever is sooner.
Time frame: Wound closure to time hospital discharge order is written or Day 30, whichever is sooner.
Population: Of the 77 subjects who were enrolled in Group 1, 56 were included in the efficacy analysis set. Of the 45 subjects who were enrolled in Group 2, 26 were included in the efficacy analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Morphine Sulfate or Sponsor-approved Equivalent | Total Opioid Burden | 96.47 mg | Standard Deviation 77.74 |
| EXPAREL | Total Opioid Burden | 32.06 mg | Standard Deviation 53.16 |
p-value: <0.0001ANOVA
Secondary
Incidence of Opioid-related Adverse Events
Incidence of opioid-related adverse events defined as somnolence, respiratory depression, hypoventilation, hypoxia, dry mouth, nausea, vomiting, constipation, sedation, confusion, pruritus, urinary retention, and postoperative ileus.
Time frame: Wound closure at time hospital discharge order is written or Day 30, whichever is sooner.
Population: Of the 77 subjects who were enrolled in Group 1, 56 were included in the efficacy analysis set. Of the 45 subjects who were enrolled in Group 2, 26 were included in the efficacy analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IV Morphine Sulfate or Sponsor-approved Equivalent | Incidence of Opioid-related Adverse Events | 23 participants |
| EXPAREL | Incidence of Opioid-related Adverse Events | 2 participants |
Secondary
Patient Satisfaction With Pain Treatment After Surgery
Responses to question pertaining to patient satisfaction with pain treatment
Time frame: Wound closure at time hospital discharge order is written or Day 30, whichever is sooner.
Population: Of the 77 subjects who were enrolled in Group 1, 56 were included in the efficacy analysis set. Of the 45 subjects who were enrolled in Group 2, 26 were included in the efficacy analysis set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IV Morphine Sulfate or Sponsor-approved Equivalent | Patient Satisfaction With Pain Treatment After Surgery | Extremely Satisfied | 30 participants |
| IV Morphine Sulfate or Sponsor-approved Equivalent | Patient Satisfaction With Pain Treatment After Surgery | Satisfied | 19 participants |
| IV Morphine Sulfate or Sponsor-approved Equivalent | Patient Satisfaction With Pain Treatment After Surgery | Neither Satisfied nor Dissatisfied | 0 participants |
| IV Morphine Sulfate or Sponsor-approved Equivalent | Patient Satisfaction With Pain Treatment After Surgery | Dissatisfied | 3 participants |
| IV Morphine Sulfate or Sponsor-approved Equivalent | Patient Satisfaction With Pain Treatment After Surgery | Extremely Dissatisfied | 1 participants |
| IV Morphine Sulfate or Sponsor-approved Equivalent | Patient Satisfaction With Pain Treatment After Surgery | Not Reported | 3 participants |
| EXPAREL | Patient Satisfaction With Pain Treatment After Surgery | Extremely Dissatisfied | 0 participants |
| EXPAREL | Patient Satisfaction With Pain Treatment After Surgery | Extremely Satisfied | 17 participants |
| EXPAREL | Patient Satisfaction With Pain Treatment After Surgery | Dissatisfied | 0 participants |
| EXPAREL | Patient Satisfaction With Pain Treatment After Surgery | Satisfied | 5 participants |
| EXPAREL | Patient Satisfaction With Pain Treatment After Surgery | Not Reported | 2 participants |
| EXPAREL | Patient Satisfaction With Pain Treatment After Surgery | Neither Satisfied nor Dissatisfied | 2 participants |