Malignant Neoplasms of Female Genital Organs, Gynecologic Cancer
Conditions
Keywords
Malignant neoplasms of female genital organs, Open gynecologic surgery, Local wound infiltration, Gynecologic cancer, Bupivacaine, Liposomal Bupivacaine, Oxycodone, ETH-Oxydose [DSC], OxyContin, OxyIR, Roxicodone, Questionnaires, Surveys, MD Anderson Symptom Inventory, MDASI, Pill diary, Medication log
Brief summary
Bupivacaine is a drug that is traditionally given as an injection to numb surgical sites. Liposomes are molecules that are similar to fats. Sometimes drugs are combined with liposomes to make them able to stay in the body for longer periods of time. This has been done with bupivacaine to create liposomal bupivacaine. The goal of this clinical research study is to compare the effects of bupivacaine to those of liposomal bupivacaine when given to patients who are having gynecologic surgery. Researchers want to compare how long the drugs work to numb the wound and how long patients take to recover from surgery.
Detailed description
Study Arms and Drug Administration: If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study arms: * If you are in Arm 1, you will receive bupivacaine only. * If you are in Arm 2, you will receive a combination of liposomal bupivacaine and bupivacaine. You will have an equal (50/50) chance of being assigned to either group. You will not know what you are receiving. However, the study staff will know what you are receiving. In both cases, the drug(s) will be injected into your skin and tissue at the end of your surgery, right before the wound is closed. Study Data Collection: Every day while you are in the hospital recovering from surgery, you will be asked questions about pain, any side effects you may be having, symptoms, and opioid use. Within 30 days after you leave the hospital, you may also be called and asked about side effects you may be having. If you are called, this call should last about 10-15 minutes. This information may also be collected during a routinely scheduled clinic visit and from the medical record. Three (3) and 7 days after you leave the hospital, and then 1 time every week after that for a total of 8 weeks, you will be called or emailed and asked questions about any symptoms you may be having. If you are called, each call should last about 10-15 minutes. If you are also enrolled on the study BS99-094 Measuring the Symptom Distress of Cancer Patients: Development of a New Assessment System, information from your participation in this study may also be collected and used in that study. Length of Study: Your participation on this study will be over 8 weeks after you leave the hospital. This is an investigational study. Both bupivacaine and liposomal bupivacaine are FDA approved and commercially available. It is investigational to compare the 2 drugs. Up to 200 participants will be enrolled in this study. All will take part at MD Anderson.
Interventions
DRUGBupivacaine
150 mg (0.25%) injected on each side of the wound at the end of surgery before wound closure.
DRUGLiposomal Bupivacaine
266 mg injected on each side of the wound at the end of surgery before wound closure.
DRUGOxycodone
1-2 tabs (5 mg) by mouth every 4 hours as needed for pain.
BEHAVIORALPill Diary
Participants complete a pill diary every day for 30 days after hospital discharge.
BEHAVIORALSymptom Questionnaire
Participants called or emailed and asked questions about symptoms three (3) and 7 days after hospital discharge, and then 1 time every week after that for a total of 8 weeks.
Sponsors
Pacira Pharmaceuticals, Inc
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Undergoing an exploratory laparotomy for suspected gynecologic cancer, which includes metastatic disease from neoplasia originating in other organs 2. Planned participation in the Gynecologic Enhanced Recovery Pathway 3. Female 18 years of age or older 4. Patient must be able to read and speak English 5. Consents to being part of a randomized, single-blinded study 6. Patient has physical and mental capabilities to take part in study 7. Bilirubin less than or equal to 1.5 x upper limit of the normal range (ULN); Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic-Pyruvic Transaminase (SGPT) \</=2.5 x ULN 8. If the patient is of childbearing potential, the patient must have a negative blood or urine pregnancy test within 14 days of surgical treatment on study
Exclusion criteria
1. Sensitivity to amide-type local anesthetics 2. Patients on long-acting opioid medications, or scheduled (four or more times a day for seven or more days) short-acting opioid medications within the last 30 days 3. Emergency surgery of any type that does not allow for proper time for protocol review by the patient 4. Surgery that involves known/anticipated resection of anterior abdominal wall with plastic surgery reconstruction 5. Patients undergoing pelvic exenteration 6. Patients undergoing known/anticipated anterior abdominal wall hernia repairs 7. Patients weighing \<50 kg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants Opioid-Free After Gynecologic Surgery for 48 Hours | 48 hours | Treatment arms compared with respect to the proportion of patients opioid-free at 48 hours using the Cochran-Mantel-Haenszel test stratified by surgeon. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants Opioid-Free After Gynecologic Surgery | 8 weeks | Treatment arms compared with respect to the number of opioid-free days using the Cochran-Mantel-Haenszel test stratified by surgeon. |
| Symptom Scores | Days 0, 2 and 4 postoperatively, up to 8 weeks | Daily pain scores were ascertained by routine nursing care every 4 hours while awake, on a 0 to 10 scale. Descriptive statistics and graphical methods used to summarize MD Anderson Symptom Inventory (MDASI) scores at each assessment time by treatment arm. For each symptom component, individuals were asked to rank symptom severity during the previous 24 hours on a scale of 0 to 10, with 0 being not present and 10 being as bad as you can imagine. Symptom interference was also assessed on a 0 to 10 scale, with 0 being did not interfere and 10 being interfered completely. Higher values represent worst outcomes. |
Countries
United States
Participant flow
Recruitment details
All patients were consented during preoperative visit at MD Anderson Cancer Center from August 31st 2016 to August 31st 2017.
Pre-assignment details
One patient was excluded after randomization because of scheduled opioid use, and 2 patients were excluded because the surgical approach changed to minimally invasive surgery (these 3 patients were never treated). All patients treated completed the trial.
Participants by arm
| Arm | Count |
|---|---|
| Active Comparator: Bupivacaine Group Local wound infiltration with Bupivacaine immediately prior to wound closure during gynecological surgery. Participants discharged with analgesic opioid regimen of Oxycodone 1-2 tabs (5mg) by mouth every 4 hours as needed for pain. Participants complete a pill diary every day for 30 days after hospital discharge. Participants called or emailed and asked questions about symptoms 3 and 7 days after hospital discharge, and then 1 time every week after that for a total of 8 weeks. | 54 |
| Experimental: Liposomal Bupivacaine + Bupivacaine Group Local wound infiltration with Liposomal Bupivacaine and 0.25% Bupivacaine admixed immediately prior to wound closure during gynecological surgery. Participants discharged with analgesic opioid regimen of Oxycodone 1-2 tabs (5 mg) by mouth every 4 hours as needed for pain. Participants complete a pill diary every day for 30 days after hospital discharge. Participants called or emailed and asked questions about symptoms 3 and 7 days after hospital discharge, and th3en 1 time every week after that for a total of 8 weeks. | 48 |
| Total | 102 |
Baseline characteristics
| Characteristic | Active Comparator: Bupivacaine Group | Experimental: Liposomal Bupivacaine + Bupivacaine Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 11 Participants | 32 Participants |
| Age, Categorical Between 18 and 65 years | 33 Participants | 37 Participants | 70 Participants |
| Age, Continuous | 62.5 years | 59 years | 61 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 41 Participants | 37 Participants | 78 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 8 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 8 Participants | 15 Participants |
| Race (NIH/OMB) White | 40 Participants | 37 Participants | 77 Participants |
| Region of Enrollment United States | 54 Participants | 48 Participants | 102 Participants |
| Sex: Female, Male Female | 54 Participants | 48 Participants | 102 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 | 0 / 54 | 0 / 48 |
| other Total, other adverse events | 0 / 54 | 0 / 48 |
| serious Total, serious adverse events | 0 / 54 | 0 / 48 |
Outcome results
Primary
Participants Opioid-Free After Gynecologic Surgery for 48 Hours
Treatment arms compared with respect to the proportion of patients opioid-free at 48 hours using the Cochran-Mantel-Haenszel test stratified by surgeon.
Time frame: 48 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Comparator: Bupivacaine Group | Participants Opioid-Free After Gynecologic Surgery for 48 Hours | 14.8 percentage of participants |
| Experimental: Liposomal Bupivacaine + Bupivacaine Group | Participants Opioid-Free After Gynecologic Surgery for 48 Hours | 16.70 percentage of participants |
Secondary
Participants Opioid-Free After Gynecologic Surgery
Treatment arms compared with respect to the number of opioid-free days using the Cochran-Mantel-Haenszel test stratified by surgeon.
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Comparator: Bupivacaine Group | Participants Opioid-Free After Gynecologic Surgery | 6 Participants |
| Experimental: Liposomal Bupivacaine + Bupivacaine Group | Participants Opioid-Free After Gynecologic Surgery | 8 Participants |
Secondary
Symptom Scores
Daily pain scores were ascertained by routine nursing care every 4 hours while awake, on a 0 to 10 scale. Descriptive statistics and graphical methods used to summarize MD Anderson Symptom Inventory (MDASI) scores at each assessment time by treatment arm. For each symptom component, individuals were asked to rank symptom severity during the previous 24 hours on a scale of 0 to 10, with 0 being not present and 10 being as bad as you can imagine. Symptom interference was also assessed on a 0 to 10 scale, with 0 being did not interfere and 10 being interfered completely. Higher values represent worst outcomes.
Time frame: Days 0, 2 and 4 postoperatively, up to 8 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Active Comparator: Bupivacaine Group | Symptom Scores | Median daily pain scores Postoperative day 0 | 2.5 score on a scale |
| Active Comparator: Bupivacaine Group | Symptom Scores | Median daily pain scores Postoperative day 2 | 2.2 score on a scale |
| Active Comparator: Bupivacaine Group | Symptom Scores | Median daily pain scores Postoperative day 4 | 0.8 score on a scale |
| Experimental: Liposomal Bupivacaine + Bupivacaine Group | Symptom Scores | Median daily pain scores Postoperative day 0 | 2.7 score on a scale |
| Experimental: Liposomal Bupivacaine + Bupivacaine Group | Symptom Scores | Median daily pain scores Postoperative day 2 | 2.5 score on a scale |
| Experimental: Liposomal Bupivacaine + Bupivacaine Group | Symptom Scores | Median daily pain scores Postoperative day 4 | 1.2 score on a scale |