Breast Cancer, Breast Cancer Female, Cancer of Breast
Conditions
Brief summary
In this double blinded randomized placebo-controlled trial, 160 subjects scheduled for breast surgery involving the axilla will be administered a multimodal pain regimen including acetaminophen, dexamethasone, celecoxib, and gabapentin. 80 subjects will also receive a Pectoral Nerve blocks I and II (PECS I and II block) preoperatively.
Interventions
DRUGBupivacaine
-Given after general anesthesia
DRUGGabapentin
* As per routine care * Will not be prescribed for any patient with preexisting kidney disease or ≥ 65 years.
DRUGCelecoxib
* As per routine care * Will not be prescribed for any patient with preexisting kidney disease or ≥ 65 years. * Naproxen will be substituted for celecoxib in patients with sulfa allergies.
DRUGAcetaminophen
-As per routine care
DRUGMidazolam
-As per routine care
DRUGFentanyl
-As per routine care
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Scheduled to undergo elective breast cancer surgeries at Barnes-Jewish Hospital: * unilateral axillary dissection * unilateral modified radical mastectomy * mastectomy with same day unilateral reconstruction * unilateral sentinel lymph node biopsy (SLNB) * partial mastectomy with unilateral SLNB * simple mastectomy with unilateral SLNB * At least 18 years of age. * Able to understand and willing to sign an Institutional Review Board (IRB)-approved written informed consent document. * Enrollment in the SATISFY-SOS study (WUSTL IRB# 201203088, NCT02032030).
Exclusion criteria
* Planned for bilateral axillary or bilateral reconstruction surgery. * Previous surgery on the surgical breast and/or axilla with the exception of partial mastectomy or sentinel lymph node biopsy * Pre-existing pain in the axilla affecting the ability to use extremity for activities of daily living or requiring medication for treatment. * Current or past medical history of liver disease or cirrhosis with an elevated INR \>1.4 or currently elevated transaminase levels. * Known contraindications to peripheral nerve block placement. * Pregnant or breastfeeding. * History of allergic reactions attributed to compounds of similar chemical or biologic composition * Planned additional surgery to the surgical breast or axilla in the next year (exception would be minor surgery to breast but not axilla such as simple tissue expander replacement or lumpectomy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Worst Pain as Measured by the Brief Pain Inventory (BPI) at 1 Year | At 1 year | * The participant is asked to rate their pain by circling the one number that best describes their pain at its worst in the past week. * 0=no pain and 10 = pain as bad as they can imagine. The higher number indicates worse pain. |
| Average Pain as Measured by the Brief Pain Inventory (BPI) at 1 Year | At 1 year | * The participant is asked to rate their pain by circling the one number that best describes their pain on the average. * 0=no pain and 10 = pain as bad as they can imagine. The higher number indicates worse pain. |
| Interference as Measured by the Brief Pain Inventory (BPI) at 1 Year | At 1 year | * The participant is asked circle the one number that describes how much, during the past week pain has interfered with general activity, mood, walking ability, normal work (includes both work outside the home and housework), relations with other people, sleep, and enjoyment of life. * 0=does not interference and 10 = completely interferes. The higher number indicates more interference from pain. * The scores for each subsection will be averaged. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life as Measured by the Veterans RAND12 Questionnaire Physical Health Summary Measure | At baseline and 1 year post-surgery | * The 12 items in the questionnaire correspond to eight principal physical and mental health domains including general health perceptions; physical functioning; role limitations due to physical and emotional problems; bodily pain; energy-fatigue, social functioning and mental health. The 12 items are summarized into two scores, a Physical Health Summary Measure (PCS) and a Mental Health Summary Measure (MCS). * The higher the score the better quality of life. * Scores are standardized to a mean of 50 with a range of -0.809-70.71. |
| Change in Quality of Life as Measured by the Veterans RAND12 Questionnaire Mental Health Summary Measure | At baseline and 1 year post-surgery | * The 12 items in the questionnaire correspond to eight principal physical and mental health domains including general health perceptions; physical functioning; role limitations due to physical and emotional problems; bodily pain; energy-fatigue, social functioning and mental health. The 12 items are summarized into two scores, a Physical Health Summary Measure (PCS) and a Mental Health Summary Measure (MCS). * The higher the score the better quality of life. * Scores are standardized to a mean of 50 with a range of -1.465-77.09. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Preoperative PECS Blocks * PECS I & II block will be administered preoperatively
* For unilateral surgeries, a PECS I block will be performed with 0.15mL/kg of 0.375% bupivacaine (maximum 10mL). The PECS II block will be performed with 0.3 mL/kg of the same solution (maximum 20mL). If there is a contralateral surgery (simple mastectomy) a PECS II block will also be performed on the other side with 0.2mL/kg of 0.375% bupivacaine (maximum 20mL)
* To ensure blind integrity, study drug syringes will be marked only study drug and subject number
* Perioperative analgesic will be encouraged.. Gabapentin 300mg, celecoxib 200mg and acetaminophen 1000mg will be administered to all patients following arrival to the preoperative area. All patients will receive premedication of 1-2 mg midazolam IV (age \< 65) and 50-100 μg fentanyl IV prior to the block placement or entry to the operating room at the discretion of the regional team or operating room anesthesiologist | 53 |
| Placebo PECS Blocks * A sham block (normal saline) will be placed preoperatively
* To ensure blind integrity, study drug syringes will be marked only study drug and subject number.
* Perioperative analgesic regimen will be encouraged. Gabapentin 300mg, celecoxib 200mg and acetaminophen 1000mg will be administered to all patients following arrival to the preoperative holding area. On the day of surgery all patients will receive premedication of 1-2 mg midazolam IV (age \< 65) and 50-100 μg fentanyl IV prior to the block placement or entry to the operating room at the discretion of the regional team or operating room anesthesiologist. | 54 |
| Not Randomized to an Arm -Participants were removed from the study prior to being randomized into an Arm. | 27 |
| Total | 134 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Determined to be ineligible | 0 | 0 | 16 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 3 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 4 |
| Overall Study | Withdrawn due to time of surgery being moved up. | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Preoperative PECS Blocks | Total | Not Randomized to an Arm | Placebo PECS Blocks |
|---|---|---|---|---|
| Age, Continuous | 57.91 years | 61.36 years | 65.46 years | 62.27 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 53 Participants | 134 Participants | 27 Participants | 54 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 19 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 43 Participants | 112 Participants | 20 Participants | 49 Participants |
| Region of Enrollment United States | 53 participants | 134 participants | 27 participants | 54 participants |
| Sex: Female, Male Female | 53 Participants | 134 Participants | 27 Participants | 54 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 53 | 0 / 54 | 1 / 27 |
| other Total, other adverse events | 5 / 53 | 0 / 54 | 0 / 0 |
| serious Total, serious adverse events | 0 / 53 | 0 / 54 | 0 / 0 |
Outcome results
Primary
Average Pain as Measured by the Brief Pain Inventory (BPI) at 1 Year
* The participant is asked to rate their pain by circling the one number that best describes their pain on the average. * 0=no pain and 10 = pain as bad as they can imagine. The higher number indicates worse pain.
Time frame: At 1 year
Population: Due to missing 1 year follow-up Brief Pain Inventories, all enrolled participants were not evaluable or included in this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Preoperative PECS Blocks | Average Pain as Measured by the Brief Pain Inventory (BPI) at 1 Year | 0 score on a scale |
| Placebo PECS Blocks | Average Pain as Measured by the Brief Pain Inventory (BPI) at 1 Year | 0 score on a scale |
p-value: 0.67Kruskal-Wallis
Primary
Interference as Measured by the Brief Pain Inventory (BPI) at 1 Year
* The participant is asked circle the one number that describes how much, during the past week pain has interfered with general activity, mood, walking ability, normal work (includes both work outside the home and housework), relations with other people, sleep, and enjoyment of life. * 0=does not interference and 10 = completely interferes. The higher number indicates more interference from pain. * The scores for each subsection will be averaged.
Time frame: At 1 year
Population: Due to missing 1 year follow-up Brief Pain Inventories, all enrolled participants were not evaluable or included in this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Preoperative PECS Blocks | Interference as Measured by the Brief Pain Inventory (BPI) at 1 Year | 0 score on a scale |
| Placebo PECS Blocks | Interference as Measured by the Brief Pain Inventory (BPI) at 1 Year | 0 score on a scale |
p-value: 0.53Kruskal-Wallis
Primary
Worst Pain as Measured by the Brief Pain Inventory (BPI) at 1 Year
* The participant is asked to rate their pain by circling the one number that best describes their pain at its worst in the past week. * 0=no pain and 10 = pain as bad as they can imagine. The higher number indicates worse pain.
Time frame: At 1 year
Population: Due to missing 1 year follow-up Brief Pain Inventories, all enrolled participants were not evaluable or included in this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Preoperative PECS Blocks | Worst Pain as Measured by the Brief Pain Inventory (BPI) at 1 Year | 0 score on a scale |
| Placebo PECS Blocks | Worst Pain as Measured by the Brief Pain Inventory (BPI) at 1 Year | 0 score on a scale |
p-value: 0.68Kruskal-Wallis
Secondary
Change in Quality of Life as Measured by the Veterans RAND12 Questionnaire Mental Health Summary Measure
* The 12 items in the questionnaire correspond to eight principal physical and mental health domains including general health perceptions; physical functioning; role limitations due to physical and emotional problems; bodily pain; energy-fatigue, social functioning and mental health. The 12 items are summarized into two scores, a Physical Health Summary Measure (PCS) and a Mental Health Summary Measure (MCS). * The higher the score the better quality of life. * Scores are standardized to a mean of 50 with a range of -1.465-77.09.
Time frame: At baseline and 1 year post-surgery
Population: Due to missing 1 year follow-up Brief Pain Inventories, all enrolled participants were not evaluable or included in this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Preoperative PECS Blocks | Change in Quality of Life as Measured by the Veterans RAND12 Questionnaire Mental Health Summary Measure | 0 score on a scale |
| Placebo PECS Blocks | Change in Quality of Life as Measured by the Veterans RAND12 Questionnaire Mental Health Summary Measure | 1.9 score on a scale |
p-value: 0.88Kruskal-Wallis
Secondary
Change in Quality of Life as Measured by the Veterans RAND12 Questionnaire Physical Health Summary Measure
* The 12 items in the questionnaire correspond to eight principal physical and mental health domains including general health perceptions; physical functioning; role limitations due to physical and emotional problems; bodily pain; energy-fatigue, social functioning and mental health. The 12 items are summarized into two scores, a Physical Health Summary Measure (PCS) and a Mental Health Summary Measure (MCS). * The higher the score the better quality of life. * Scores are standardized to a mean of 50 with a range of -0.809-70.71.
Time frame: At baseline and 1 year post-surgery
Population: Due to missing 1 year follow-up Brief Pain Inventories, all enrolled participants were not evaluable or included in this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Preoperative PECS Blocks | Change in Quality of Life as Measured by the Veterans RAND12 Questionnaire Physical Health Summary Measure | -3.1 score on a scale |
| Placebo PECS Blocks | Change in Quality of Life as Measured by the Veterans RAND12 Questionnaire Physical Health Summary Measure | -0.8 score on a scale |
p-value: 0.44Kruskal-Wallis