Analgesia, Surgery
Conditions
Brief summary
The goal of this study is to test the hypothesis that surgical site infiltration with liposomal bupivacaine (LB) is non-inferior to and more cost effective than thoracic epidural analgesia (TEA) for patients undergoing open gynecologic surgery on an established enhanced recovery program (ERP) using a non-inferiority randomized trial design. The impact of TEA and surgical site infiltration with LB on neuroendocrine and inflammatory mediators of surgical stress response (SSR) will also be investigated as a translational endpoint.
Interventions
DRUGLiposomal bupivacaine
Surgical site infiltration with 20 mL liposomal bupivacaine prior to laparotomy closure.
OTHERThoracic epidural analgesia (bupivacaine)
Perioperative bupivacaine based thoracic epidural placed preoperatively.
Sponsors
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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
Yes
Inclusion criteria
* Individuals ≥ 18 years of age * Planned laparotomy by the gynecologic oncology service at the sponsor institution.
Exclusion criteria
* Individuals who have a contraindication to thoracic epidural analgesia * Individuals with a coagulation disorder * Individuals with an infection at the site of epidural placement * Individuals with intracranial pathology such as non-communicating increased intracranial pressure or obstruction of cerebrospinal fluid flow related to mass lesions * Individuals with spinal pathology: abnormal spine anatomy, surgical fusion, or spinal column lesions * Individuals who have a contraindication to liposomal bupivacaine * Individuals with a known allergic reaction to liposomal bupivacaine * Individuals with Childs-Pugh Class B or C liver disease * Individuals who have a history of long-term opioid use for chronic pain, defined as use of opioid pain medications for ≥4 weeks prior to surgery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Analgesia Assessed by the Area Under the Curve of Visual Analog Scale Pain Intensity Scores | 0 to 48 hours postoperatively | Pain intensity was measured using the Visual Analog Scale (VAS), a 0-10 scale where 0 indicates no pain and 10 indicates worst pain imaginable. VAS scores were assessed hourly from 0 to 48 hours postoperatively. The area under the curve (AUC) was calculated as the sum of hourly VAS scores over 48 hours, yielding a possible range of 0 to 480. Higher scores indicate greater cumulative pain burden and worse outcomes. |
| Total Opioid Consumption | 0 to 48 hours postoperatively | Total opioid consumption in IV mg morphine equivalents from 0 to 48 hours postoperatively will be compared between the two arms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient-perceived Quality of Recovery as Assessed by the Quality of Recovery-15 Instrument (QoR-15) | Days 1 through 7 post-intervention | Mean patient-perceived quality of recovery scores using the Quality of Recovery-15 instrument (QoR-15) on postoperative days 1 to 7 were compared between the two arms. The QoR-15 is a validated instrument designed to measure the major domains of postoperative recovery with a score range of 0 indicating the poorest patient-perceived quality of recovery to 150 indicating the highest patient-perceived quality of recovery. QoR-15 scores were analyzed using a linear mixed-effects model for repeated measures across postoperative days 1-7. The single value reported for each arm represents the model-based estimated marginal mean (least squares mean) across all assessed postoperative days using all available observed data without imputation. This reflects an overall POD1-7 summary rather than a score from a single postoperative day. |
| Time (Days) to Return of Bowel Function (ROBF) | Up to 7 days post-intervention | Time to ROBF is defined as the time lapse from the day of surgery (DOS) to the day oral intake is consistently tolerated for 48 hours without vomiting. |
| Number of Participants With Postoperative Ileus | Up to 7 days post-intervention | Ileus is defined as the occurrence of postoperative nausea and vomiting requiring cessation of oral intake and initiation of intravenous hydration +/- nasogastric tube placement following documented ROBF or the persistence of these symptoms beyond postoperative day 5 in the absence of ROBF. |
| Mobility as Assessed by the Johns Hopkins Highest Level of Mobility (JH-HLM) Scale | Up to 7 days post-intervention | The Johns Hopkins Highest Level of Mobility (JH-HLM) scale is an ordinal scale ranging from 1 to 8, with higher scores indicating better mobility. Scores represent observed mobility milestones achieved by the patient; a score of 1 indicates lying in bed, while a score of 8 indicates walking 250 feet or more. Mobility was analyzed using a linear mixed-effects model for repeated measures across postoperative days 1-7. The single value reported for each arm represents the model-based estimated marginal mean (least squares mean) across all assessed postoperative days using all available observed data without imputation. This reflects an overall POD1-7 summary rather than a single postoperative day. |
| Number of Participants With Sedation Score ≥2 as Assessed by the Pasero Opioid-Induced Sedation Scale | Up to 7 days post-intervention | The Pasero Opioid-induced Sedation Scale (POSS) is a valid, reliable tool used to assess sedation when administering opioid medications to manage pain. It uses an ordinal scale of 1-4 with a POSS of 1 or 2 indicating an acceptable level of sedation and a score of 3 or 4 indicating over-sedation and the need for intervention, such as the administration of a reversal agent in the case of a score of 4. |
| Length of Stay | Up to 1 year | The duration of the index inpatient postoperative admission in days. |
| Time to Postoperative Diuresis | Arrival in recovery through hospital discharge, up to 1 year | Time to diuresis is defined as the recovery time in hours to achieve a net negative fluid balance sustained over a 24 hour time period. |
| Total Intravenous Fluids Administered in mL | Arrival in recovery through hospital discharge, up to 1 year | Total intravenous fluids administered in mL. |
| Amount of Vasopressor Required | Start of operation through hospital discharge, up to 1 year | Total amount (micrograms) of Levophed required. |
| Duration of Vasopressor Administration | Start of operation through hospital discharge, up to 1 year | Duration (minutes) of vasopressor administration. |
| Number Participants With Postoperative Complications | Day of admission through postoperative day 30 | Number of participants with postoperative complications (Maryland Hospital Acquired Conditions). |
| Total Direct Cost of TEA Placement and LB Surgical Site Infiltration | Up to 1 year | Total Direct Cost (Pharmacy and equipment costs, professional fees and the dollar-value of total OR time required for administration of each intervention) |
| Post-discharge Narcotic Utilization | Postoperative day 14 | Patient reported total outpatient narcotic use in IV morphine (mg) equivalents on nurse phone survey administered on postoperative day 14. |
| Number of Participants With 30-day Hospital Readmission | Up to 30 days post discharge from index admission | Number of participants with 30-day hospital readmission assessed as the number of participants who get readmitted within 30 days of discharge from the initial admission. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRebecca L Stone, MD
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Participant flow
Recruitment details
Patients were recruited from the gynecologic oncology service at a single academic medical center. Potentially eligible participants undergoing planned midline laparotomy will be identified through surgical schedules and clinic visits. Patients will be approached preoperatively by study personnel, and informed consent will be obtained prior to enrollment.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 53.69 Years STANDARD_DEVIATION 14.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 74 Participants |
| Sex: Female, Male Female | 49 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 50 |
| other Total, other adverse events | 31 / 49 | 31 / 50 |
| serious Total, serious adverse events | 0 / 49 | 0 / 50 |
Outcome results
None listed