Post-op Pain
Conditions
Keywords
Hip replacement, Knee replacement, randomized trial, acetaminophen, post-op pain management
Brief summary
The purpose of the study is to evaluate post-op pain requirements in patients undergoing hip or knee replacement surgery who perioperatively receive either Oral acetaminophen or IV acetaminophen
Detailed description
Subjects will be randomized to receive perioperative dosing of either: 1. Oral acetaminophen (Tylenol) 1000mg with IV Placebo (100ml Normal Saline), OR, 2. IV acetaminophen (Ofirmev) 1000mg/100ml with Oral Placebo (oral capsules). Subject pain levels and post-operative opioid use will be tracked for up to 24 hours after surgery.
Interventions
Subjects randomized to the Oral acetaminophen arm will receive 2 Tylenol 500mg capsules. In this study, one arm receives an oral form of active medication and one arm receives an IV form of active medication. To keep the subject and study personnel blinded, subjects receiving Oral acetaminophen will also receive 100ml of IV Normal Saline similar to the delivery method of the IV acetaminophen arm. The Normal Saline IV placebo will be given not as an intervention but rather as a method to maintain study integrity.
DRUGIV acetaminophen
Subjects randomized to the IV acetaminophen arm will receive Ofirmev 1000mg in 100ml Normal Saline IV plus 2 placebo capsules. In this study, one arm receives an oral form of active medication and one arm receives an IV form of active medication. To keep the subject and study personnel blinded, subjects receiving IV acetaminophen will also receive 2 placebo capsules similar to the delivery method of the oral acetaminophen arm. The placebo capsules will be given not as an intervention but rather as a method to maintain study integrity.
Sponsors
Kettering Health Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age and older * Able to provide written consent * Able to read and write in English * Weighing over 50 kg * Will undergo total hip or total knee joint replacement
Exclusion criteria
* Non-verbal patients * Unable to use numeric pain scale * Allergic to the test article * Documented hepatic impairment or failure * Current illicit drug use * Requires traumatic or emergent surgery * Pregnant women * Women who are breastfeeding * Prisoners * Cognitively impaired requiring Legally Authorized Representative (LAR) or Power of Attorney (POA) * Unable to swallow oral capsules
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Post-operative Use of Opioids | During post-op period up to 24 hrs after surgery | Post-operative use of opioids, measured in morphine milligram equivalent (MME) units |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient-rated Pain in the Post-operative Period | Standard-of-care post-op assessment intervals during post-op period up to 24 hrs after surgery | Patient-rated pain in the post-operative period was collected using a 10-point visual analog scale (VAS). A score of 0 indicates no pain; higher scores indicate greater pain. Minimum score for each VAS measurement is 0; Maximum score for each VAS measurement is 10. VAS scores were averaged for each patient. |
Other
| Measure | Time frame |
|---|---|
| Time to First Rescue Opioid (PRN Order) | During post-op period up to 24 hrs after surgery |
| Time to First Ambulation - 10 Feet | During post-op period up to 24 hours after surgery |
| Post-operative Nausea and Vomiting | During post-op period up to 24 hrs after surgery |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oral Acetaminophen Subjects receive 2 capsules each containing Tylenol 500 mg caplets. The test article administration will be initiated 60 minutes (± 15 minutes) prior to the scheduled surgery start time.
Oral acetaminophen: Subjects randomized to the Oral acetaminophen arm will receive 2 Tylenol 500mg capsules. In this study, one arm receives an oral form of active medication and one arm receives an IV form of active medication. To keep the subject and study personnel blinded, subjects receiving Oral acetaminophen will also receive 100ml of IV Normal Saline similar to the delivery method of the IV acetaminophen arm. The Normal Saline IV placebo will be given not as an intervention but rather as a method to maintain study integrity. | 241 |
| IV Acetaminophen Subjects receive Ofirmev 1000 mg in 100 ml Normal Saline IV infusion. The test article will be given perioperatively at the discretion of the attending anesthesiologist.
IV acetaminophen: Subjects randomized to the IV acetaminophen arm will receive Ofirmev 1000mg in 100ml Normal Saline IV plus 2 placebo capsules. In this study, one arm receives an oral form of active medication and one arm receives an IV form of active medication. To keep the subject and study personnel blinded, subjects receiving IV acetaminophen will also receive 2 placebo capsules similar to the delivery method of the oral acetaminophen arm. The placebo capsules will be given not as an intervention but rather as a method to maintain study integrity. | 245 |
| Total | 486 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not receive study intervention | 8 | 21 |
Baseline characteristics
| Characteristic | Oral Acetaminophen | IV Acetaminophen | Total |
|---|---|---|---|
| Age, Continuous | 67.0 years | 67.0 years | 67.0 years |
| Body mass index | 31.9 lb/in^2x703 | 32.3 lb/in^2x703 | 32.1 lb/in^2x703 |
| Diabetes | 48 Participants | 50 Participants | 98 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 5 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 237 Participants | 240 Participants | 477 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Intra-operative Bupivacaine Liposome Injectable Suspension | 163 Participants | 162 Participants | 325 Participants |
| Intra-operative Ketorolac | 35 Participants | 36 Participants | 71 Participants |
| Intra-operative total opioid | 10.0 morphine milligram equivalents (MME) | 10.0 morphine milligram equivalents (MME) | 10.0 morphine milligram equivalents (MME) |
| Oxford score (hip or knee as appropriate) | 20.76 units on a scale STANDARD_DEVIATION 7.5 | 20.19 units on a scale STANDARD_DEVIATION 7.8 | 20.47 units on a scale STANDARD_DEVIATION 7.6 |
| Pre-operative Celecoxib | 198 Participants | 195 Participants | 393 Participants |
| Pre-operative opioid | 50 Participants | 57 Participants | 107 Participants |
| Pre-operative Pregabalin | 230 Participants | 232 Participants | 462 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 11 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 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 | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 234 Participants | 230 Participants | 464 Participants |
| Sex: Female, Male Female | 148 Participants | 140 Participants | 288 Participants |
| Sex: Female, Male Male | 93 Participants | 105 Participants | 198 Participants |
| Stroke | 5 Participants | 4 Participants | 9 Participants |
| Taking medications for chronic pain | 214 Participants | 212 Participants | 426 Participants |
| Type of surgery Hip | 73 Participants | 75 Participants | 148 Participants |
| Type of surgery Knee | 168 Participants | 170 Participants | 338 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 241 | 0 / 245 |
| other Total, other adverse events | 0 / 241 | 0 / 245 |
| serious Total, serious adverse events | 0 / 241 | 0 / 245 |
Outcome results
Primary
Total Post-operative Use of Opioids
Post-operative use of opioids, measured in morphine milligram equivalent (MME) units
Time frame: During post-op period up to 24 hrs after surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oral Acetaminophen | Total Post-operative Use of Opioids | 21.7 Morphine milligram equivalents (MME) |
| IV Acetaminophen | Total Post-operative Use of Opioids | 21.7 Morphine milligram equivalents (MME) |
Secondary
Patient-rated Pain in the Post-operative Period
Patient-rated pain in the post-operative period was collected using a 10-point visual analog scale (VAS). A score of 0 indicates no pain; higher scores indicate greater pain. Minimum score for each VAS measurement is 0; Maximum score for each VAS measurement is 10. VAS scores were averaged for each patient.
Time frame: Standard-of-care post-op assessment intervals during post-op period up to 24 hrs after surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oral Acetaminophen | Patient-rated Pain in the Post-operative Period | 3.6 Visual analog pain scale (0-10) |
| IV Acetaminophen | Patient-rated Pain in the Post-operative Period | 3.4 Visual analog pain scale (0-10) |
Post Hoc
Hospital Length of Stay (LOS)
Total hospital length of stay was calculated as (hospital discharge moment - hospital admission moment). Hospital length of stay is reported in hours.
Time frame: Pre-op admission to hospital discharge
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oral Acetaminophen | Hospital Length of Stay (LOS) | 58.0 Hours |
| IV Acetaminophen | Hospital Length of Stay (LOS) | 58.5 Hours |
Post Hoc
Post-Anesthesia Care Unit (PACU) Length of Stay, Hours
PACU length of stay was calculated as (PACU discharge moment - PACU admit moment). PACU length of stay is reported in hours.
Time frame: PACU admission time until PACU discharge time
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oral Acetaminophen | Post-Anesthesia Care Unit (PACU) Length of Stay, Hours | 2.2 Hours |
| IV Acetaminophen | Post-Anesthesia Care Unit (PACU) Length of Stay, Hours | 2.1 Hours |
Other Pre-specified
Post-operative Nausea and Vomiting
Time frame: During post-op period up to 24 hrs after surgery
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oral Acetaminophen | Post-operative Nausea and Vomiting | Nausea | 51 Participants |
| Oral Acetaminophen | Post-operative Nausea and Vomiting | Vomiting | 19 Participants |
| IV Acetaminophen | Post-operative Nausea and Vomiting | Nausea | 53 Participants |
| IV Acetaminophen | Post-operative Nausea and Vomiting | Vomiting | 17 Participants |
Other Pre-specified
Time to First Ambulation - 10 Feet
Time frame: During post-op period up to 24 hours after surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oral Acetaminophen | Time to First Ambulation - 10 Feet | 18.5 Hours |
| IV Acetaminophen | Time to First Ambulation - 10 Feet | 18.8 Hours |
Other Pre-specified
Time to First Rescue Opioid (PRN Order)
Time frame: During post-op period up to 24 hrs after surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oral Acetaminophen | Time to First Rescue Opioid (PRN Order) | 38.0 Minutes |
| IV Acetaminophen | Time to First Rescue Opioid (PRN Order) | 41.0 Minutes |