Postoperative Pain
Conditions
Brief summary
Effective post-surgical pain management is a crucial component of a patient's postoperative course following posterior colporrhaphy. Narcotics are the cornerstone for postoperative analgesia with a frequent re-dosing requirement, a lengthy list of side effects and adverse reaction risks. The colorectal, orthopedic and general surgery literatures have reported on an extended-release bupivacaine liposomal injection, Exparel®, which remarkably reduces acute post-operative pain; however, literature regarding this medication specific to Urogynecology and Gynecology is limited. The investigators propose a prospective, randomized, double blind, trial with 120 subjects recruited from the Walter Reed National Military Medical Center (WRNMMC) Urogynecology Clinic to study postsurgical pain control after posterior repair. There will be two arms in the study; one arm with bupivacaine alone and a second arm with bupivacaine mixed with Exparel®(extended-release, liposomal bupivacaine) injected vaginally in patients undergoing posterior colporrhaphy. Subjects will be randomized to receive either 20 milliliter (mL) of plain bupivacaine or 20mL (10ml+10ml) mixture of bupivacaine plus Exparel®. The primary objective of the trial will be to evaluate the postsurgical vaginal pain using a visual analog pain scale at days 1, 2, 3 post-procedure. All subjects will have acetaminophen, a non-steroidal anti-inflammatory drug and narcotic pain medication available for pain control regardless of assignment, which is the usual postoperative pain control regimen. The investigators hypothesize a 30% difference in post-operative pain measurements between the two groups. Additional objectives of this study are to evaluate total medication usage on days 1, 2 and 3 and any post-operative voiding and defecatory dysfunction, comparing the two groups
Interventions
DRUGExparel plus plain bupivacaine
10 mL of extended release liposomal bupivacaine (Exparel) plus 10 mL of 0.25% plain bupivacaine mixed to be injected vaginally prior to the start of posterior colporrhaphy
DRUGBupivacaine
20 mL of 0.25% plain bupivacaine to be injected vaginally prior to the start of posterior colporrhaphy
Sponsors
Walter Reed National Military Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
* Females \>18 years of age undergoing Urogynecologic surgery involving the posterior vaginal wall mucosa or muscularis including posterior colporrhaphy at Walter Reed National Military Medical Center. * Patients must be able to read and understand written English or have an appropriate certified medical translator available.
Exclusion criteria
* Known allergy to amide local anesthetics. * Unstable cardiac arrhythmia. * Hepatic impairment (including but not limited to patients under the care of their physician for severe hepatic disease, cirrhosis or hepatic cancer). * Known pregnancy at time of surgery (pregnancy test morning of surgery if applicable). * Regular use of narcotic pain medication, defined as use on most days of week at any time in the three months prior to surgery. * Significant history of opioid or alcohol abuse or addiction (requiring treatment). * Concurrent pain management requiring the use of epidural anesthesia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Vaginal Pain Scores Using the Defense and Veterans Pain Rating Scale (Visual Analog Scale) Between Bupivacaine Alone Versus Exparel® Following Posterior Colporrhaphy Post-operatively | Subjects will be asked to provide numerical values on postoperative day 1. | Patients will be asked on postoperative day (POD) 1 to provide numerical values regarding vaginal pain from 0-10 (zero being no pain and 10 being the worst pain) utilizing the Defense and Veterans Pain Rating Scale (visual analog scale) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Amount Acetaminophen Pain Medication Required During the Postoperative Period at Home | Calculated with phone call on postoperative day 1, 2, and 3 (total acetaminophen utilized at home) | Calculate total postoperative acetaminophen used while at home via perform pill counts on postoperative days 1, 2, 3 (done via a phone call). This will allow calculation of total amount of acetaminophen utilized at home through postoperative day #3 |
| Amount Opioid Pain Medication Required During the Postoperative Period (Through Day 3) | Calculated throughout hospitalization and/or with phone call on postoperative day 1, 2, and 3 (total opioids utilized) | Calculate total postoperative opioid medications used while inpatient and perform pill counts on postoperative days 1, 2, 3 (done via a phone call or inpatient). This will allow calculation of total amount of opioid pain medications utilized through postoperative day #3 |
| Percentage of Participants Who Passed Active Voiding Trial Comparing the Bupivacaine Plus Exparel® Group Versus the Bupivacaine Plain Group. | Postoperative active voiding trial on postoperative day 1. | Investigators will record in patients passed active voiding trail prior to discharge home. |
| Rate of Post-operative Defecatory Function After Posterior Colporrhaphy, Comparing the Bupivacaine Plus Exparel® Group Versus the Bupivacaine Plain Group. | Postoperatively up to day 3 | Investigators will record in patients have had a bowel movement within the first three days postoperatively. |
| Amount Ibuprofen Pain Medication Required During the Postoperative Period at Home | Calculated with phone call on postoperative day 1, 2, and 3 (total acetaminophen utilized at home) | Calculate total postoperative ibuprofen used while at home via perform pill counts on postoperative days 1, 2, 3 (done via a phone call). This will allow calculation of total amount of ibuprofen utilized at home through postoperative day #3 |
| Impact of Vaginal Pain Scores on Quality of Life Measure (SLEEP) Using Defense and Veterans Pain Rating Scale (Visual Analog Scale) Comparing the Bupivacaine Plus Exparel® Group and the Bupivacaine Plain Group | Subjects will be asked to provide numerical value on postoperative day 3. | Investigators will ask patients how is your vaginal pain impacting your SLEEP (quality of life question) and respond using a 0-10 answer (0 being no impact and 10 being significant impact) using the Defense and Veterans Pain Rating Scale (visual analog scale). This will be recorded on POD 3 |
| Impact of Vaginal Pain Scores on Quality of Life Measure (MOOD) Using Defense and Veterans Pain Rating Scale (Visual Analog Scale) Comparing the Bupivacaine Plus Exparel® Group and the Bupivacaine Plain Group | Subjects will be asked to provide numerical value on postoperative day 3. | Investigators will ask patients how is your vaginal pain impacting your MOOD (quality of life question) and respond using a 0-10 answer (0 being no impact and 10 being significant impact) using the Defense and Veterans Pain Rating Scale (visual analog scale). This will be recorded on POD 3 |
| Impact of Vaginal Pain Scores on Quality of Life Measure (STRESS) Using Defense and Veterans Pain Rating Scale (Visual Analog Scale) Comparing the Bupivacaine Plus Exparel® Group and the Bupivacaine Plain Group | Subjects will be asked to provide numerical value on postoperative day 3. | Investigators will ask patients how is your vaginal pain impacting your STRESS (quality of life question) and respond using a 0-10 answer (0 being no impact and 10 being significant impact) using the Defense and Veterans Pain Rating Scale (visual analog scale). This will be recorded on POD 3 |
| Impact of Vaginal Pain Scores on Quality of Life Measures (ACTIVITY) Using Defense and Veterans Pain Rating Scale (Visual Analog Scale) Comparing the Bupivacaine Plus Exparel® Group and the Bupivacaine Plain Group | Subjects will be asked to provide numerical value on postoperative day 3. | Investigators will ask patients how is your vaginal pain impacting your ACTIVITY (quality of life question) and respond using a 0-10 answer (0 being no impact and 10 being significant impact) using the Defense and Veterans Pain Rating Scale (visual analog scale). This will be recorded on POD 3 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Plain Bupivacaine 20 mL of 0.25% plain bupivacaine
Bupivacaine: 20 mL of 0.25% plain bupivacaine to be injected vaginally prior to the start of posterior colporrhaphy | 60 |
| Exparel Plus Plain Bupivacaine 10 mL of extended release liposomal bupivacaine (Exparel) plus 10 mL of 0.25% plain bupivacaine mixed
Exparel plus plain bupivacaine: 10 mL of extended release liposomal bupivacaine (Exparel) plus 10 mL of 0.25% plain bupivacaine mixed to be injected vaginally prior to the start of posterior colporrhaphy | 60 |
| Total | 120 |
Baseline characteristics
| Characteristic | Exparel Plus Plain Bupivacaine | Total | Plain Bupivacaine |
|---|---|---|---|
| Age, Continuous Exparel Plus Plain Bupivacaine | 51.0 years | 51.0 years | — |
| Age, Continuous Plain Bupivacaine | — | 49.5 years | 49.5 years |
| Body Mass Index Exparel plus plain bupivacaine | 25.9 kg/m^2 | 25.9 kg/m^2 | — |
| Body Mass Index Plain Bupivacaine | — | 26.1 kg/m^2 | 26.1 kg/m^2 |
| colpopexy laparoscopic | 31 Participants | 63 Participants | 32 Participants |
| colpopexy none | 9 Participants | 21 Participants | 12 Participants |
| colpopexy vaginal | 20 Participants | 36 Participants | 16 Participants |
| Gravidity Exparel plus plain bupivacaine | 3 pregnancies | 3 pregnancies | — |
| Gravidity Plain Bupivacaine | — | 3 pregnancies | 3 pregnancies |
| hysterectomy laparoscopic | 22 Participants | 52 Participants | 30 Participants |
| hysterectomy none | 25 Participants | 46 Participants | 21 Participants |
| hysterectomy vaginal | 13 Participants | 22 Participants | 9 Participants |
| Parity Exparel plus plain bupivacaine | 3 births | 3 births | — |
| Parity Plain Bupivacaine | — | 2 births | 2 births |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 16 Participants | 7 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 8 Participants | 6 Participants |
| Race (NIH/OMB) White | 48 Participants | 94 Participants | 46 Participants |
| Sex: Female, Male Female | 60 Participants | 120 Participants | 60 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 / 60 | 0 / 60 |
| other Total, other adverse events | 3 / 60 | 4 / 60 |
| serious Total, serious adverse events | 0 / 60 | 0 / 60 |
Outcome results
Primary
Change in Vaginal Pain Scores Using the Defense and Veterans Pain Rating Scale (Visual Analog Scale) Between Bupivacaine Alone Versus Exparel® Following Posterior Colporrhaphy Post-operatively
Patients will be asked on postoperative day (POD) 2 to provide numerical values for vaginal pain from 0-10 (zero being no pain and 10 being the worst pain) utilizing the Defense and Veterans Pain Rating Scale (visual analog scale)
Time frame: Subjects will be asked to provide numerical values on postoperative day 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plain Bupivacaine | Change in Vaginal Pain Scores Using the Defense and Veterans Pain Rating Scale (Visual Analog Scale) Between Bupivacaine Alone Versus Exparel® Following Posterior Colporrhaphy Post-operatively | 3 score on a scale |
| Exparel Plus Plain Bupivacaine | Change in Vaginal Pain Scores Using the Defense and Veterans Pain Rating Scale (Visual Analog Scale) Between Bupivacaine Alone Versus Exparel® Following Posterior Colporrhaphy Post-operatively | 2 score on a scale |
Primary
Change in Vaginal Pain Scores Using the Defense and Veterans Pain Rating Scale (Visual Analog Scale) Between Bupivacaine Alone Versus Exparel® Following Posterior Colporrhaphy Post-operatively
Patients will be asked on postoperative day (POD) 3 to provide numerical values for vaginal pain from 0-10 (zero being no pain and 10 being the worst pain) utilizing the Defense and Veterans Pain Rating Scale (visual analog scale)
Time frame: Subjects will be asked to provide numerical values on postoperative day 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plain Bupivacaine | Change in Vaginal Pain Scores Using the Defense and Veterans Pain Rating Scale (Visual Analog Scale) Between Bupivacaine Alone Versus Exparel® Following Posterior Colporrhaphy Post-operatively | 3 score on a scale |
| Exparel Plus Plain Bupivacaine | Change in Vaginal Pain Scores Using the Defense and Veterans Pain Rating Scale (Visual Analog Scale) Between Bupivacaine Alone Versus Exparel® Following Posterior Colporrhaphy Post-operatively | 2 score on a scale |
Primary
Change in Vaginal Pain Scores Using the Defense and Veterans Pain Rating Scale (Visual Analog Scale) Between Bupivacaine Alone Versus Exparel® Following Posterior Colporrhaphy Post-operatively
Patients will be asked on postoperative day (POD) 1 to provide numerical values regarding vaginal pain from 0-10 (zero being no pain and 10 being the worst pain) utilizing the Defense and Veterans Pain Rating Scale (visual analog scale)
Time frame: Subjects will be asked to provide numerical values on postoperative day 1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plain Bupivacaine | Change in Vaginal Pain Scores Using the Defense and Veterans Pain Rating Scale (Visual Analog Scale) Between Bupivacaine Alone Versus Exparel® Following Posterior Colporrhaphy Post-operatively | 2 score on a scale |
| Exparel Plus Plain Bupivacaine | Change in Vaginal Pain Scores Using the Defense and Veterans Pain Rating Scale (Visual Analog Scale) Between Bupivacaine Alone Versus Exparel® Following Posterior Colporrhaphy Post-operatively | 0 score on a scale |
Secondary
Amount Acetaminophen Pain Medication Required During the Postoperative Period at Home
Calculate total postoperative acetaminophen used while at home via perform pill counts on postoperative days 1, 2, 3 (done via a phone call). This will allow calculation of total amount of acetaminophen utilized at home through postoperative day #3
Time frame: Calculated with phone call on postoperative day 1, 2, and 3 (total acetaminophen utilized at home)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plain Bupivacaine | Amount Acetaminophen Pain Medication Required During the Postoperative Period at Home | 4000 milligrams |
| Exparel Plus Plain Bupivacaine | Amount Acetaminophen Pain Medication Required During the Postoperative Period at Home | 3250 milligrams |
Secondary
Amount Ibuprofen Pain Medication Required During the Postoperative Period at Home
Calculate total postoperative ibuprofen used while at home via perform pill counts on postoperative days 1, 2, 3 (done via a phone call). This will allow calculation of total amount of ibuprofen utilized at home through postoperative day #3
Time frame: Calculated with phone call on postoperative day 1, 2, and 3 (total acetaminophen utilized at home)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plain Bupivacaine | Amount Ibuprofen Pain Medication Required During the Postoperative Period at Home | 3600 milligrams |
| Exparel Plus Plain Bupivacaine | Amount Ibuprofen Pain Medication Required During the Postoperative Period at Home | 2400 milligrams |
Secondary
Amount Opioid Pain Medication Required During the Postoperative Period (Through Day 3)
Calculate total postoperative opioid medications used while inpatient and perform pill counts on postoperative days 1, 2, 3 (done via a phone call or inpatient). This will allow calculation of total amount of opioid pain medications utilized through postoperative day #3
Time frame: Calculated throughout hospitalization and/or with phone call on postoperative day 1, 2, and 3 (total opioids utilized)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plain Bupivacaine | Amount Opioid Pain Medication Required During the Postoperative Period (Through Day 3) | 45.0 morphine milligram equivalents |
| Exparel Plus Plain Bupivacaine | Amount Opioid Pain Medication Required During the Postoperative Period (Through Day 3) | 57.1 morphine milligram equivalents |
Secondary
Impact of Vaginal Pain Scores on Quality of Life Measure (MOOD) Using Defense and Veterans Pain Rating Scale (Visual Analog Scale) Comparing the Bupivacaine Plus Exparel® Group and the Bupivacaine Plain Group
Investigators will ask patients how is your vaginal pain impacting your MOOD (quality of life question) and respond using a 0-10 answer (0 being no impact and 10 being significant impact) using the Defense and Veterans Pain Rating Scale (visual analog scale). This will be recorded on POD 3
Time frame: Subjects will be asked to provide numerical value on postoperative day 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plain Bupivacaine | Impact of Vaginal Pain Scores on Quality of Life Measure (MOOD) Using Defense and Veterans Pain Rating Scale (Visual Analog Scale) Comparing the Bupivacaine Plus Exparel® Group and the Bupivacaine Plain Group | 1 score on a scale |
| Exparel Plus Plain Bupivacaine | Impact of Vaginal Pain Scores on Quality of Life Measure (MOOD) Using Defense and Veterans Pain Rating Scale (Visual Analog Scale) Comparing the Bupivacaine Plus Exparel® Group and the Bupivacaine Plain Group | 1 score on a scale |
Secondary
Impact of Vaginal Pain Scores on Quality of Life Measures (ACTIVITY) Using Defense and Veterans Pain Rating Scale (Visual Analog Scale) Comparing the Bupivacaine Plus Exparel® Group and the Bupivacaine Plain Group
Investigators will ask patients how is your vaginal pain impacting your ACTIVITY (quality of life question) and respond using a 0-10 answer (0 being no impact and 10 being significant impact) using the Defense and Veterans Pain Rating Scale (visual analog scale). This will be recorded on POD 3
Time frame: Subjects will be asked to provide numerical value on postoperative day 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plain Bupivacaine | Impact of Vaginal Pain Scores on Quality of Life Measures (ACTIVITY) Using Defense and Veterans Pain Rating Scale (Visual Analog Scale) Comparing the Bupivacaine Plus Exparel® Group and the Bupivacaine Plain Group | 3.5 score on a scale |
| Exparel Plus Plain Bupivacaine | Impact of Vaginal Pain Scores on Quality of Life Measures (ACTIVITY) Using Defense and Veterans Pain Rating Scale (Visual Analog Scale) Comparing the Bupivacaine Plus Exparel® Group and the Bupivacaine Plain Group | 3 score on a scale |
Secondary
Impact of Vaginal Pain Scores on Quality of Life Measure (SLEEP) Using Defense and Veterans Pain Rating Scale (Visual Analog Scale) Comparing the Bupivacaine Plus Exparel® Group and the Bupivacaine Plain Group
Investigators will ask patients how is your vaginal pain impacting your SLEEP (quality of life question) and respond using a 0-10 answer (0 being no impact and 10 being significant impact) using the Defense and Veterans Pain Rating Scale (visual analog scale). This will be recorded on POD 3
Time frame: Subjects will be asked to provide numerical value on postoperative day 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plain Bupivacaine | Impact of Vaginal Pain Scores on Quality of Life Measure (SLEEP) Using Defense and Veterans Pain Rating Scale (Visual Analog Scale) Comparing the Bupivacaine Plus Exparel® Group and the Bupivacaine Plain Group | 0.500 score on a scale |
| Exparel Plus Plain Bupivacaine | Impact of Vaginal Pain Scores on Quality of Life Measure (SLEEP) Using Defense and Veterans Pain Rating Scale (Visual Analog Scale) Comparing the Bupivacaine Plus Exparel® Group and the Bupivacaine Plain Group | 1 score on a scale |
Secondary
Impact of Vaginal Pain Scores on Quality of Life Measure (STRESS) Using Defense and Veterans Pain Rating Scale (Visual Analog Scale) Comparing the Bupivacaine Plus Exparel® Group and the Bupivacaine Plain Group
Investigators will ask patients how is your vaginal pain impacting your STRESS (quality of life question) and respond using a 0-10 answer (0 being no impact and 10 being significant impact) using the Defense and Veterans Pain Rating Scale (visual analog scale). This will be recorded on POD 3
Time frame: Subjects will be asked to provide numerical value on postoperative day 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plain Bupivacaine | Impact of Vaginal Pain Scores on Quality of Life Measure (STRESS) Using Defense and Veterans Pain Rating Scale (Visual Analog Scale) Comparing the Bupivacaine Plus Exparel® Group and the Bupivacaine Plain Group | 0 score on a scale |
| Exparel Plus Plain Bupivacaine | Impact of Vaginal Pain Scores on Quality of Life Measure (STRESS) Using Defense and Veterans Pain Rating Scale (Visual Analog Scale) Comparing the Bupivacaine Plus Exparel® Group and the Bupivacaine Plain Group | 1 score on a scale |
Secondary
Percentage of Participants Who Passed Active Voiding Trial Comparing the Bupivacaine Plus Exparel® Group Versus the Bupivacaine Plain Group.
Investigators will record in patients passed active voiding trail prior to discharge home.
Time frame: Postoperative active voiding trial on postoperative day 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Plain Bupivacaine | Percentage of Participants Who Passed Active Voiding Trial Comparing the Bupivacaine Plus Exparel® Group Versus the Bupivacaine Plain Group. | 82 percentage passed |
| Exparel Plus Plain Bupivacaine | Percentage of Participants Who Passed Active Voiding Trial Comparing the Bupivacaine Plus Exparel® Group Versus the Bupivacaine Plain Group. | 72 percentage passed |
Secondary
Rate of Post-operative Defecatory Function After Posterior Colporrhaphy, Comparing the Bupivacaine Plus Exparel® Group Versus the Bupivacaine Plain Group.
Investigators will record in patients have had a bowel movement within the first three days postoperatively.
Time frame: Postoperatively up to day 3
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Plain Bupivacaine | Rate of Post-operative Defecatory Function After Posterior Colporrhaphy, Comparing the Bupivacaine Plus Exparel® Group Versus the Bupivacaine Plain Group. | 71.6 percentage of patients |
| Exparel Plus Plain Bupivacaine | Rate of Post-operative Defecatory Function After Posterior Colporrhaphy, Comparing the Bupivacaine Plus Exparel® Group Versus the Bupivacaine Plain Group. | 73.3 percentage of patients |