Malignant Female Reproductive System Neoplasm
Conditions
Brief summary
This phase IV trial studies how well liposomal bupivacaine with or without hydromorphone works in improving pain control during the first 24 hours after surgery in patients with gynecological malignancies undergoing laparotomy. Liposomal bupivacaine is routinely infiltrated into the skin surrounding the abdominal incision, and is effective in providing good relief of incisional pain. Hydromorphone is also a type of pain medication that may provide better management of deep abdominal pain. It is not yet known if giving liposomal bupivacaine with or without hydromorphone will work better in improving pain in patients with gynecological malignancies during the first 24 hours after surgery.
Detailed description
PRIMARY OBJECTIVES: I. Evaluate if no additional intervention is noninferior to intrathecal analgesia (ITA) for postoperative pain experience 24 hours after surgery after laparotomy for gynecological malignancy within an established enhanced recovery pathway which includes incisional liposomal bupivacaine (ILB). II. Evaluate the effect of intrathecal analgesia on patient satisfaction with postoperative analgesia after laparotomy for gynecological malignancy. III. Report the impact of ITA use on cost. IV. Validate the Quality of Recovery (QOR)-15 in our population. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo standard of care laparotomy and then receive liposomal bupivacaine. ARM II: Patients undergo standard of care laparotomy and then receive liposomal bupivacaine and hydromorphone intrathecally (IT).
Interventions
DRUGHydromorphone
Given IT
PROCEDURELaparotomy
Undergo laparotomy
DRUGLiposomal Bupivacaine
Drug
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Elective surgery for suspected (based on consulting surgeon's opinion-imaging, laboratory \[lab\], pathology \[path\]) gynecological malignancy, enhanced recovery after surgery (ERAS) protocol
Exclusion criteria
* Inability to read or understand English * Prehospitalization narcotic use if weekly average daily oral morphine equivalent of \> 20 mg * Chronic pain syndromes such as fibromyalgia * Extensive surgery planned (surrogate for post-operative \[postop\] pain): Planned intensive care unit (ICU) admission, abdominoperineal resection, exenteration, use of intraoperative radiation (IORT), hyperthermic intraperitoneal chemotherapy (HIPEC) * Contraindication to neuraxial analgesia: * Coagulopathy * International normalized ratio (INR) \> 1.2 current or predicted after surgery (e.g. planned right hepatic resection) * Thrombocytopenia. Platelets (plts) \< 100 * Hemophiliac disease states (hemophilia, von Willebrand disease, etc.) * Patients receiving antithrombotic or thrombolytic therapy are excluded according to the American Society of Regional Anesthesia and Pain Medicine (ASRA) guidelines * Localized infection at the potential site of injection * Significant developmental or structural spinal abnormalities that would preclude a safe spinal technique. These include spina bifida, tethered spinal cord, lumbar spinal fusion, and active lumbar radiculopathy * Patients with stage 4 or 5 kidney disease (glomerular filtration rate \[GFR\] less than 30 ml/min per 1.73 m\^2) * Intolerance or allergy to opioids, acetaminophen, or amide-type local anesthetics * Current pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Benefit of Analgesia Score (OBAS) | Up to 24 hours after surgery | The Overall Benefit of Analgesia Score (OBAS) is a multi-dimensional survey that measures a patient's benefit from postoperative pain therapy. It assesses pain intensity, opioid-related adverse events, and patient satisfaction with analgesia. Each of 7 questions are scored on a scale from 0 to 4 where 0=minimal/not at all and 4=maximum/very much. The total score is a sum of the 7 item scores with question 7 scored as 4 minus the patient reported number. Total scores range from 0 to 28 with lower scores representing greater benefit from analgesic therapy. The median total OBAS score for each group is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative 24-hour Narcotic Consumption | Up to 24 hours after surgery | Various narcotic medications are standardized and reported as Morphine Milligram Equivalents (MME). |
| Post-operative Pain Scores | Up to 24 hours after surgery | Postoperative pain is scored on a scale of 0 - 10, with the lower score showing a better outcome. |
| Time to First Analgesic Request | Up to 24 hours after surgery | Amount of time from leaving surgery to the first request for pain relief. |
| Use of Intravenous (IV) Patient-controlled Analgesia | Up to 24 hours after surgery | Number of patients that used IV, patient controlled analgesia after surgery. |
| Use of Intravenous Rescue Opioids | Up to 24 hours after surgery | Number of patients that needed IV rescue opioids after surgery. |
| Length of Stay | Up to 1 week after surgery | Length of associated hospitalization in days. |
| Weight Gain Following Surgery | Up to 24 hours after surgery | Weight difference post- and pre-surgery. |
| Total Cost of Care | Entire hospitalization, approximately 2-5 days | All medical costs occurring during hospitalization. |
| Incidence of Adverse Events | Up to 24 hours after surgery | Reported as the number participants reporting one or more adverse events on each study arm. |
| Operating Room Time | Approximately 8 hours | Length of time from when the patient entered the operating room to when they left. |
| Surgical Time | Approximately 8 hours | Time from first incision to surgical site closure. |
| Pain Management | Whole hospitalization, approximately 2-5 days | Pharmaceutical costs associated with pain management. |
| Additional Fluid Requirement After 24 Hours of Surgery | Up to 24 hours after surgery | Number of patients requiring additional IV fluids after surgery. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Quality of Recovery-15 (QoR-15) Total Score | At 24 hours after surgery | The Quality of Recovery (QoR-15) questionnaire is a 15-item survey that patients rate to measure the quality of their recovery after surgery. Each item in the questionnaire is graded on an 11-point numeric rating scale with total scores ranging from 15 to 150. Higher scores indicate better recovery. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Laparotomy, Liposomal Bupivacaine) Patients undergo standard of care laparotomy and then receive liposomal bupivacaine.
Laparotomy: Undergo laparotomy
Liposomal Bupivacaine: Drug
Questionnaire Administration: Ancillary studies | 59 |
| Arm II (Laparotomy, Liposomal Bupivacaine, Hydromorphone) Patients undergo standard of care laparotomy and then receive liposomal bupivacaine and hydromorphone IT.
Hydromorphone: Given IT
Laparotomy: Undergo laparotomy
Liposomal Bupivacaine: Drug
Questionnaire Administration: Ancillary studies | 46 |
| Total | 105 |
Baseline characteristics
| Characteristic | Arm I (Laparotomy, Liposomal Bupivacaine) | Arm II (Laparotomy, Liposomal Bupivacaine, Hydromorphone) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 28 Participants | 22 Participants | 50 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 24 Participants | 55 Participants |
| Age, Continuous | 56 years | 56.5 years | 56 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 0 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants | 46 Participants | 101 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 55 Participants | 46 Participants | 101 Participants |
| Region of Enrollment United States | 59 participants | 46 participants | 105 participants |
| Sex: Female, Male Female | 59 Participants | 46 Participants | 105 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 / 59 | 0 / 46 |
| other Total, other adverse events | 0 / 59 | 0 / 46 |
| serious Total, serious adverse events | 0 / 59 | 1 / 46 |
Outcome results
Primary
Overall Benefit of Analgesia Score (OBAS)
The Overall Benefit of Analgesia Score (OBAS) is a multi-dimensional survey that measures a patient's benefit from postoperative pain therapy. It assesses pain intensity, opioid-related adverse events, and patient satisfaction with analgesia. Each of 7 questions are scored on a scale from 0 to 4 where 0=minimal/not at all and 4=maximum/very much. The total score is a sum of the 7 item scores with question 7 scored as 4 minus the patient reported number. Total scores range from 0 to 28 with lower scores representing greater benefit from analgesic therapy. The median total OBAS score for each group is presented.
Time frame: Up to 24 hours after surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Laparotomy, Liposomal Bupivacaine) | Overall Benefit of Analgesia Score (OBAS) | 4 score on a scale |
| Arm II (Laparotomy, Liposomal Bupivacaine, Hydromorphone) | Overall Benefit of Analgesia Score (OBAS) | 4 score on a scale |
Secondary
Additional Fluid Requirement After 24 Hours of Surgery
Number of patients requiring additional IV fluids after surgery.
Time frame: Up to 24 hours after surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Laparotomy, Liposomal Bupivacaine) | Additional Fluid Requirement After 24 Hours of Surgery | 27 Participants |
| Arm II (Laparotomy, Liposomal Bupivacaine, Hydromorphone) | Additional Fluid Requirement After 24 Hours of Surgery | 24 Participants |
Secondary
Cumulative 24-hour Narcotic Consumption
Various narcotic medications are standardized and reported as Morphine Milligram Equivalents (MME).
Time frame: Up to 24 hours after surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Laparotomy, Liposomal Bupivacaine) | Cumulative 24-hour Narcotic Consumption | 41.4 Morphine Milligram Equivalents (MME) | Standard Deviation 31.9 |
| Arm II (Laparotomy, Liposomal Bupivacaine, Hydromorphone) | Cumulative 24-hour Narcotic Consumption | 17.5 Morphine Milligram Equivalents (MME) | Standard Deviation 25 |
Secondary
Incidence of Adverse Events
Reported as the number participants reporting one or more adverse events on each study arm.
Time frame: Up to 24 hours after surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Laparotomy, Liposomal Bupivacaine) | Incidence of Adverse Events | 0 Participants |
| Arm II (Laparotomy, Liposomal Bupivacaine, Hydromorphone) | Incidence of Adverse Events | 1 Participants |
Secondary
Length of Stay
Length of associated hospitalization in days.
Time frame: Up to 1 week after surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Laparotomy, Liposomal Bupivacaine) | Length of Stay | 3.8 days |
| Arm II (Laparotomy, Liposomal Bupivacaine, Hydromorphone) | Length of Stay | 3.4 days |
Secondary
Operating Room Time
Length of time from when the patient entered the operating room to when they left.
Time frame: Approximately 8 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Laparotomy, Liposomal Bupivacaine) | Operating Room Time | 6.2 hours |
| Arm II (Laparotomy, Liposomal Bupivacaine, Hydromorphone) | Operating Room Time | 5.8 hours |
Secondary
Pain Management
Pharmaceutical costs associated with pain management.
Time frame: Whole hospitalization, approximately 2-5 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Laparotomy, Liposomal Bupivacaine) | Pain Management | 830 dollars |
| Arm II (Laparotomy, Liposomal Bupivacaine, Hydromorphone) | Pain Management | 807 dollars |
Secondary
Post-operative Pain Scores
Postoperative pain is scored on a scale of 0 - 10, with the lower score showing a better outcome.
Time frame: Up to 24 hours after surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Laparotomy, Liposomal Bupivacaine) | Post-operative Pain Scores | 4 score on a scale |
| Arm II (Laparotomy, Liposomal Bupivacaine, Hydromorphone) | Post-operative Pain Scores | 3 score on a scale |
Secondary
Surgical Time
Time from first incision to surgical site closure.
Time frame: Approximately 8 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Laparotomy, Liposomal Bupivacaine) | Surgical Time | 4.5 hours |
| Arm II (Laparotomy, Liposomal Bupivacaine, Hydromorphone) | Surgical Time | 4.4 hours |
Secondary
Time to First Analgesic Request
Amount of time from leaving surgery to the first request for pain relief.
Time frame: Up to 24 hours after surgery
Population: Analyses were based on treatment received, not randomization arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Laparotomy, Liposomal Bupivacaine) | Time to First Analgesic Request | 20.1 minutes |
| Arm II (Laparotomy, Liposomal Bupivacaine, Hydromorphone) | Time to First Analgesic Request | 25.0 minutes |
Secondary
Total Cost of Care
All medical costs occurring during hospitalization.
Time frame: Entire hospitalization, approximately 2-5 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Laparotomy, Liposomal Bupivacaine) | Total Cost of Care | 30109 dollars |
| Arm II (Laparotomy, Liposomal Bupivacaine, Hydromorphone) | Total Cost of Care | 27776 dollars |
Secondary
Use of Intravenous (IV) Patient-controlled Analgesia
Number of patients that used IV, patient controlled analgesia after surgery.
Time frame: Up to 24 hours after surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Laparotomy, Liposomal Bupivacaine) | Use of Intravenous (IV) Patient-controlled Analgesia | 3 Participants |
| Arm II (Laparotomy, Liposomal Bupivacaine, Hydromorphone) | Use of Intravenous (IV) Patient-controlled Analgesia | 5 Participants |
Secondary
Use of Intravenous Rescue Opioids
Number of patients that needed IV rescue opioids after surgery.
Time frame: Up to 24 hours after surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Laparotomy, Liposomal Bupivacaine) | Use of Intravenous Rescue Opioids | 42 Participants |
| Arm II (Laparotomy, Liposomal Bupivacaine, Hydromorphone) | Use of Intravenous Rescue Opioids | 12 Participants |
Secondary
Weight Gain Following Surgery
Weight difference post- and pre-surgery.
Time frame: Up to 24 hours after surgery
Population: Data not collected
Other Pre-specified
Quality of Recovery-15 (QoR-15) Total Score
The Quality of Recovery (QoR-15) questionnaire is a 15-item survey that patients rate to measure the quality of their recovery after surgery. Each item in the questionnaire is graded on an 11-point numeric rating scale with total scores ranging from 15 to 150. Higher scores indicate better recovery.
Time frame: At 24 hours after surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Laparotomy, Liposomal Bupivacaine) | Quality of Recovery-15 (QoR-15) Total Score | 95.5 score on a scale |
| Arm II (Laparotomy, Liposomal Bupivacaine, Hydromorphone) | Quality of Recovery-15 (QoR-15) Total Score | 104.0 score on a scale |