Opioid Use, Pain, Postoperative
Conditions
Brief summary
This is a double blinded randomized controlled trial to test the efficacy of a combination of acetaminophen and ibuprofen administered to patients on schedule compared to ibuprofen alone on the patient's reported pain score on the second post-operative day after Cesarean delivery. The investigators will also record opiate consumption and pain scores throughout the hospitalization of participants, and will survey patients at one and two weeks after surgery regarding opiate consumption and quality of life.
Detailed description
The investigators have designed a double-blinded randomized, controlled trial to compare a standardized pain regimen of scheduled ibuprofen and acetaminophen to scheduled ibuprofen and placebo. In both arms, the participant will have the ability to ask for medication for breakthrough pain which will be oxycodone. By standardizing and scheduling the administration of ibuprofen with acetaminophen, the investigators hypothesize that total opioid requested and therefore consumed will be decreased in this participants who receive ibuprofen scheduled with acetaminophen. The investigators will primarily assess pain as reported on a 10-point scale mid-day on the second post-operative day. Secondarily, the investigators will collect reported pain scores and total opiate consumption while in the hospital, opiate consumption after discharge, and quality of life as assessed by the World Health Organization Quality of Life Bref (WHOQOL-BREF) survey. This information will be obtained via chart review and at-home surveys administered via email on the Research Electronic Data Capture (REDCap) system one and two weeks after surgery. Enrollment will be performed by study staff. Participants will then be randomized by the institution's Investigational Drug Services (IDS) in REDCap, which uses a randomization table generated by Penn State University (PSU) bio-statisticians. A medication packet will then be prepared and distributed by IDS for the participant containing 20 tablets of acetaminophen 650 mg or placebo based on randomization assignment. The packet will then be sent to nursing staff caring for the patient. Participants will then receive study medication/placebo along with ibuprofen 600 mg (dispensed by the clinical pharmacy) every 6 hours. Participants will be able to request medication for breakthrough pain which will be oxycodone 5 mg or 10 mg depending on reported pain score (one pill for moderate pain, two pills for severe pain). Both ibuprofen and oxycodone will be ordered and dispensed by the clinical pharmacy. Until the participant is deemed able to receive medication by mouth, the participant may receive medication as prescribed by the caring obstetrician and/or anesthesiologist which will be beyond the scope of this trial. Pain scores will be collected and recorded in the medical chart by nursing and assistant staff as part of routine care. At discharge, participants will receive a standard prescription for 20 tablets of oxycodone 5 mg with directions to take 1-2 tablets every 6-8 hours as needed for breakthrough pain, as is the current group standard at the institution in the Department of Obstetrics and Gynecology. After discharge, study staff will then conduct a chart review to collect demographic information, review the operative report, and ensure no event took place which would exclude the participant from the study. Study staff will also record total opiate consumption and pain scores. One week after surgery, the participant will receive an invitation via electronic mail (e-mail) to complete a survey on REDCap which will assess opiate consumption and perceived appropriateness of pain control. Two weeks after surgery, participants will receive two additional invitations; one to complete another survey to assess opiate consumption and perceived appropriateness of pain control, and a second to complete the WHOQOL-BREF. The WHOQOL-BREF survey has been validated to assess four distinct categories of quality of life in women two weeks postpartum. These invitations and reminders have been designed to occur automatically with the assistance of features inherent to the REDCap program. Participants will be considered non-compliant if they fail to complete surveys within three days of receiving their invitation.
Interventions
DRUGAcetaminophen
Acetaminophen 650 mg tablet every 6 hours
DRUGPlacebo
Placebo oral tablet every 6 hours
DRUGIbuprofen
Ibuprofen 600 mg tablet every 6 hours
Sponsors
Milton S. Hershey 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 No maximum
Healthy volunteers
No
Inclusion criteria
* Pregnant women at least 18 years of age * Planned delivery via C-section * Pfannenstiel skin incision * Lower uterine segment transverse hysterotomy * English speaking
Exclusion criteria
* Major intra-operative or post-operative complication such that clinician recommends patient should not receive non-steroidal anti-inflammatory drugs or that patient requires acetaminophen to treat fever (ie suspected endometritis) * Unplanned surgery (hysterectomy, bowel/bladder repair) * Allergy or contraindication to study medication * Non-English speaking * Inability to provide informed consent * History of opioid, other illicit substance, or alcohol use disorder either before or during pregnancy * Severe renal or hepatic impairment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Score | Post-operative day 2, corresponding to 2 days after cesarean section surgery (day of surgery is considered post-operative day 0). Measurement taken mid-day (12 PM - 4 PM) | Pain score on a scale of 0 (no pain) to 10 (worst pain); pain score is a verbal report of participant pain on a scale of 0-10, 0 indicating no pain and incrementally increasing as integer to a maximum score of 10 indicating the most severe pain possible. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Opiate Consumption in Hospital | Post-operative day 0 (day of surgery) until discharged from hospital on post-operative day 3 or 4. | Total number of oxycodone 5 mg tablets taken during hospital admission after cesarean section surgery |
| WHOQOL-BREF Score, Domain 1 | Post-operative Day 14 (two weeks after cesarean section surgery) | Domain Score on World Health Organization Quality of Life - Brief (WHOQOL-BREF) survey. The survey consists of 26 questions and evaluates four domains of quality of life including physical health (domain 1), psychological (domain 2), social relationships (domain 3), and environment (domain 4). Domain scores are scaled in a positive direction (i.e. higher scores denote higher quality of life) and range between 4-20, comparable with the WHOQOL-100. |
| WHOQOL-BREF Score, Domain 2 | Post-operative Day 14 (two weeks after cesarean section surgery) | Domain Score on World Health Organization Quality of Life - Brief (WHOQOL-BREF) survey. The survey consists of 26 questions and evaluates four domains of quality of life including physical health (domain 1), psychological (domain 2), social relationships (domain 3), and environment (domain 4). Domain scores are scaled in a positive direction (i.e. higher scores denote higher quality of life) and range between 4-20, comparable with the WHOQOL-100. |
| WHOQOL-BREF Score, Domain 3 | Post-operative Day 14 (two weeks after cesarean section surgery) | Domain Score on World Health Organization Quality of Life - Brief (WHOQOL-BREF) survey. The survey consists of 26 questions and evaluates four domains of quality of life including physical health (domain 1), psychological (domain 2), social relationships (domain 3), and environment (domain 4). Domain scores are scaled in a positive direction (i.e. higher scores denote higher quality of life) and range between 4-20, comparable with the WHOQOL-100. |
| WHOQOL-BREF Score, Domain 4 | Post-operative Day 14 (two weeks after cesarean section surgery) | Domain Score on World Health Organization Quality of Life - Brief (WHOQOL-BREF) survey. The survey consists of 26 questions and evaluates four domains of quality of life including physical health (domain 1), psychological (domain 2), social relationships (domain 3), and environment (domain 4). Domain scores are scaled in a positive direction (i.e. higher scores denote higher quality of life) and range between 4-20, comparable with the WHOQOL-100. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ibuprofen and Placebo Oral administration of ibuprofen 600 mg tablet and placebo tablet every 6 hours
Placebo: Placebo oral tablet every 6 hours
Ibuprofen: Ibuprofen 600 mg tablet every 6 hours | 20 |
| Ibuprofen and Acetaminophen Oral administration of ibuprofen 600 mg tablet and acetaminophen 650 mg tablet every 6 hours
Acetaminophen: Acetaminophen 650 mg tablet every 6 hours
Ibuprofen: Ibuprofen 600 mg tablet every 6 hours | 21 |
| Total | 41 |
Baseline characteristics
| Characteristic | Ibuprofen and Acetaminophen | Total | Ibuprofen and Placebo |
|---|---|---|---|
| Age, Continuous | 30.0 years STANDARD_DEVIATION 9.8 | 30.3 years STANDARD_DEVIATION 7.8 | 30.6 years STANDARD_DEVIATION 5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 10 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 31 Participants | 17 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 | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 7 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 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 | 4 Participants | 2 Participants |
| Race (NIH/OMB) White | 12 Participants | 26 Participants | 14 Participants |
| Sex: Female, Male Female | 21 Participants | 41 Participants | 20 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 / 20 | 0 / 21 |
| other Total, other adverse events | 0 / 20 | 0 / 21 |
| serious Total, serious adverse events | 0 / 20 | 0 / 21 |
Outcome results
Primary
Pain Score
Pain score on a scale of 0 (no pain) to 10 (worst pain); pain score is a verbal report of participant pain on a scale of 0-10, 0 indicating no pain and incrementally increasing as integer to a maximum score of 10 indicating the most severe pain possible.
Time frame: Post-operative day 2, corresponding to 2 days after cesarean section surgery (day of surgery is considered post-operative day 0). Measurement taken mid-day (12 PM - 4 PM)
Population: Participants having a post-op day 2 (mid-day) pain score in their charts.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ibuprofen and Placebo | Pain Score | 3.5 score on a scale | Standard Deviation 2.3 |
| Ibuprofen and Acetaminophen | Pain Score | 3.3 score on a scale | Standard Deviation 2.4 |
Secondary
Opiate Consumption in Hospital
Total number of oxycodone 5 mg tablets taken during hospital admission after cesarean section surgery
Time frame: Post-operative day 0 (day of surgery) until discharged from hospital on post-operative day 3 or 4.
Population: Subjects with available data in their charts
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ibuprofen and Placebo | Opiate Consumption in Hospital | 10 number of tablets |
| Ibuprofen and Acetaminophen | Opiate Consumption in Hospital | 9 number of tablets |
Secondary
WHOQOL-BREF Score, Domain 1
Domain Score on World Health Organization Quality of Life - Brief (WHOQOL-BREF) survey. The survey consists of 26 questions and evaluates four domains of quality of life including physical health (domain 1), psychological (domain 2), social relationships (domain 3), and environment (domain 4). Domain scores are scaled in a positive direction (i.e. higher scores denote higher quality of life) and range between 4-20, comparable with the WHOQOL-100.
Time frame: Post-operative Day 14 (two weeks after cesarean section surgery)
Population: subjects completing this survey
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ibuprofen and Placebo | WHOQOL-BREF Score, Domain 1 | 15.6 score on a scale | Standard Deviation 2.3 |
| Ibuprofen and Acetaminophen | WHOQOL-BREF Score, Domain 1 | 16.2 score on a scale | Standard Deviation 2.6 |
Secondary
WHOQOL-BREF Score, Domain 2
Domain Score on World Health Organization Quality of Life - Brief (WHOQOL-BREF) survey. The survey consists of 26 questions and evaluates four domains of quality of life including physical health (domain 1), psychological (domain 2), social relationships (domain 3), and environment (domain 4). Domain scores are scaled in a positive direction (i.e. higher scores denote higher quality of life) and range between 4-20, comparable with the WHOQOL-100.
Time frame: Post-operative Day 14 (two weeks after cesarean section surgery)
Population: subjects completing this survey
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ibuprofen and Placebo | WHOQOL-BREF Score, Domain 2 | 15.6 score on a scale | Standard Deviation 2.8 |
| Ibuprofen and Acetaminophen | WHOQOL-BREF Score, Domain 2 | 16.4 score on a scale | Standard Deviation 1.7 |
Secondary
WHOQOL-BREF Score, Domain 3
Domain Score on World Health Organization Quality of Life - Brief (WHOQOL-BREF) survey. The survey consists of 26 questions and evaluates four domains of quality of life including physical health (domain 1), psychological (domain 2), social relationships (domain 3), and environment (domain 4). Domain scores are scaled in a positive direction (i.e. higher scores denote higher quality of life) and range between 4-20, comparable with the WHOQOL-100.
Time frame: Post-operative Day 14 (two weeks after cesarean section surgery)
Population: subjects completing this survey
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ibuprofen and Placebo | WHOQOL-BREF Score, Domain 3 | 15.4 score on a scale | Standard Deviation 2.9 |
| Ibuprofen and Acetaminophen | WHOQOL-BREF Score, Domain 3 | 17.1 score on a scale | Standard Deviation 2.3 |
Secondary
WHOQOL-BREF Score, Domain 4
Domain Score on World Health Organization Quality of Life - Brief (WHOQOL-BREF) survey. The survey consists of 26 questions and evaluates four domains of quality of life including physical health (domain 1), psychological (domain 2), social relationships (domain 3), and environment (domain 4). Domain scores are scaled in a positive direction (i.e. higher scores denote higher quality of life) and range between 4-20, comparable with the WHOQOL-100.
Time frame: Post-operative Day 14 (two weeks after cesarean section surgery)
Population: subjects who completed the survey
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ibuprofen and Placebo | WHOQOL-BREF Score, Domain 4 | 17.2 score on a scale | Standard Deviation 1.8 |
| Ibuprofen and Acetaminophen | WHOQOL-BREF Score, Domain 4 | 17.1 score on a scale | Standard Deviation 1.6 |