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The primary objective of this trial is to determine whether the combination of three non-opioid analgesics (multimodal analgesia) can significantly reduce or eliminate the need for opioids after ambulatory surgery.
A secondary objective would be to present credible data for insurance providers about the opioid sparing effect of these medications. This data may encourage insurance providers to support payment for short term use of certain analgesics that currently require prior authorization.
Prescription opioids are associated with addiction and accidental overdose, yet they continue to be the most commonly prescribed analgesics after ambulatory surgery.
Multimodal analgesia is a promising alternative to opioids. It is based on the theory that a combination of more than one analgesic (with non-opioid mechanisms of action) can provide pain relief equal to or exceeding that of traditional opioids.
Multimodal analgesia is not associated with opioid related side effects such as respiratory depression, nausea, constipation, and itching.
Implementation of multi-modal analgesia in an ambulatory setting is challenging for a number of reasons.
First, patient compliance with multiple medications and complex dosing schedules is poor.
Second, misinformation still exists about the dosing of acetaminophen and NSAIDS (non-steroidal anti-inflammatory drugs). For example, many patients and health care providers believe that acetaminophen and NSAIDS cannot be taken concurrently. As a result, the additive analgesic effect of combining these drugs is not achieved.
Finally, some medications used for multimodal analgesia can be difficult to procure in the ambulatory setting. For example, pregabalin (trade name Lyrica) has been used successfully to treat acute pain and reduce opioid requirements after surgery. However, its mechanism of action is similar to that of gabapentin (an older and less expensive drug) and insurers are reluctant to approve its use over the expensive alternative.
Although gabapentin is a useful analgesic for chronic pain, its delayed onset of activity and unpredictable blood levels after oral administration make it impractical to use in the setting of acute pain. In fact, optimal dosing of gabapentin may require several days or weeks to establish.By contrast, pregabalin has a rapid onset of action with consistent and predictable plasma levels after oral administration.
For this trial, patients in the control group would receive traditional postoperative pain medication consisting of a combination of oxycodone and acetaminophen (trade name Percocet) as needed at 4-6 hour intervals.
Patients in the study group would receive the following:
The principles of postoperative pain management addressed in this protocol are supported by existing literature.
The primary objective of this trial is to determine whether the combination of three non-opioid analgesics (multimodal analgesia) can significantly reduce or eliminate the need for opioids after ambulatory surgery.
A secondary objective would be to present credible data for insurance providers about the opioid sparing effect of these medications. This data may encourage insurance providers to support payment for short term use of certain analgesics that currently require prior authorization.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| multi-modal | Experimental | 3 Different Non-opioid pain medication taken every 6 hours Celecoxib 100mg Acetaminophen 325mg Pregabalin 50 mg Plus, for breakthrough pain oxycodone 5-10 mg will be taken every 4 hours as needed for pain. |
|
| Control | Active Comparator | 7 day supply of Percocet (oxycodone 5mg/acetaminophen 325 mg) to be taken 1-2 by mouth every 4 hours as needed for pain. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Celecoxib | Drug | Celecoxib 100mg |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Amount of Pain Experienced | Pain as measured by a 0-10 Visual Analog Scale (VAS) pain scale, where "0" is the lowest score and "10" is the highest score. For example, 10 would be severe pain and 0 would be none. Cumulative scores were the total scores over 6 days and were expressed with the absolute totals with range. No subscales were used. Cumulative scores represent the absolute sum of each data point for 6 days. The total cumulative range for pain is 0-60. | Cumulative every day after 6 days post-operative |
| Measure | Description | Time Frame |
|---|---|---|
| Amount of Nausea Experienced | Nausea as measured by a 0-10 Visual Analog Scale (VAS) nausea scale, where "0" is the lowest score and "10" is the highest score. For example, 10 would be severe nausea and 0 would be none. Cumulative scores were the total scores over 6 days and were expressed with the absolute totals with range. No subscales were used. Cumulative scores represent the absolute sum of each data point for 6 days. The total cumulative range for nausea is 0-60. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jeffrey Swenson, MS | University of Utah | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Utah | Salt Lake City | Utah | 84112 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36518729 | Derived | Swenson JD, Conrad KM, Pace NL, Phillips K, Saltzman CL. Scheduled, Simultaneous Dosing of Pregabalin, Celecoxib, and Acetaminophen Markedly Reduces or Eliminates Opioid Use After ACL Reconstruction Using Allograft or Hamstring Tendon Autograft: A Randomized Clinical Trial. Orthop J Sports Med. 2022 Dec 8;10(12):23259671221140837. doi: 10.1177/23259671221140837. eCollection 2022 Dec. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Multi-modal | 3 Different Non-opioid pain medication taken every 6 hours Celecoxib 100mg Acetaminophen 325mg Pregabalin 50 mg Plus, for breakthrough pain oxycodone 5-10 mg will be taken every 4 hours as needed for pain. Celecoxib: Celecoxib 100mg Acetaminophen: Acetaminophen 325mg Pregabalin: Pregabalin 50 mg Oxycodone: oxycodone 5-10 mg |
| FG001 | Control | 7 day supply of Percocet (oxycodone 5mg/acetaminophen 325 mg) to be taken 1-2 by mouth every 4 hours as needed for pain. Percocet: Percocet (oxycodone 5mg/acetaminophen 325 mg) |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Participant characteristics and anesthetics drugs
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| ID | Title | Description |
|---|---|---|
| BG000 | Multi-modal | 3 Different Non-opioid pain medication taken every 6 hours Celecoxib 100mg Acetaminophen 325mg Pregabalin 50 mg Plus, for breakthrough pain oxycodone 5-10 mg will be taken every 4 hours as needed for pain. Celecoxib: Celecoxib 100mg Acetaminophen: Acetaminophen 325mg Pregabalin: Pregabalin 50 mg Oxycodone: oxycodone 5-10 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Amount of Pain Experienced | Pain as measured by a 0-10 Visual Analog Scale (VAS) pain scale, where "0" is the lowest score and "10" is the highest score. For example, 10 would be severe pain and 0 would be none. Cumulative scores were the total scores over 6 days and were expressed with the absolute totals with range. No subscales were used. Cumulative scores represent the absolute sum of each data point for 6 days. The total cumulative range for pain is 0-60. | Posted | Median | Inter-Quartile Range | Score on a scale | Cumulative every day after 6 days post-operative |
|
6 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Multi-modal | 3 Different Non-opioid pain medication taken every 6 hours Celecoxib 100mg Acetaminophen 325mg Pregabalin 50 mg Plus, for breakthrough pain oxycodone 5-10 mg will be taken every 4 hours as needed for pain. Celecoxib: Celecoxib 100mg Acetaminophen: Acetaminophen 325mg Pregabalin: Pregabalin 50 mg Oxycodone: oxycodone 5-10 mg |
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An important limitation of this trial is the inability to discern the true effects of medication delivery and medications received. This effect could only be measured by studying these 2 interventions separately. Similarly, this dosing regimen was applied to patients with a fixed range of weights and ages. The study design may have discouraged patients who prefer opioid analgesia. This could cause a sampling bias leading only patients motivated to use less opioid to participate.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jeffrey D. Swenson | University of Utah | 801-581-6393 | jeff.swenson@hsc.utah.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 6, 2020 | Apr 19, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000068579 | Celecoxib |
| D000082 | Acetaminophen |
| D000069583 | Pregabalin |
| D010098 | Oxycodone |
| C514822 | oxycodone-acetaminophen |
| ID | Term |
|---|---|
| D000096926 | Benzenesulfonamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
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| Acetaminophen | Drug | Acetaminophen 325mg |
|
|
| Pregabalin | Drug | Pregabalin 50 mg |
|
|
| Oxycodone | Drug | oxycodone 5-10 mg |
|
|
| Percocet | Drug | Percocet (oxycodone 5mg/acetaminophen 325 mg) |
|
|
| Cumulative every day after 6 days post-operative |
| Amount of Itching Experienced | Itching as measured by a 0-10 Visual Analog Scale (VAS) itching scale, where "0" is the lowest score and "10" is the highest score. For example, 10 would be severe itching and 0 would be none. Cumulative scores were the total scores over 6 days and were expressed with the absolute totals with range. No subscales were used. Cumulative scores represent the absolute sum of each data point for 6 days. The total cumulative range for itching is 0-60. | Cumulative every day after 6 days post-operative |
| Amount of Oxycodone Used | Oxycodone use, measured by number of 5-mg tablets as standard dose | Cumulative every day after 6 days post-operative |
| BG001 |
| Control |
7 day supply of Percocet (oxycodone 5mg/acetaminophen 325 mg) to be taken 1-2 by mouth every 4 hours as needed for pain. Percocet: Percocet (oxycodone 5mg/acetaminophen 325 mg) |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Height | Mean | Standard Deviation | cm |
|
| Weight | Mean | Standard Deviation | kg |
|
| Body mass index | Mean | Standard Deviation | kg/m^2 |
|
| Scopolamine patch | Count of Participants | Participants |
|
| Intraoperative fentanyl | Mean | Standard Deviation | mg |
|
| PACU fentanyl | Mean | Standard Deviation | mg |
|
| OG001 | Control | 7 day supply of Percocet (oxycodone 5mg/acetaminophen 325 mg) to be taken 1-2 by mouth every 4 hours as needed for pain. Percocet: Percocet (oxycodone 5mg/acetaminophen 325 mg) |
|
|
| Secondary | Amount of Nausea Experienced | Nausea as measured by a 0-10 Visual Analog Scale (VAS) nausea scale, where "0" is the lowest score and "10" is the highest score. For example, 10 would be severe nausea and 0 would be none. Cumulative scores were the total scores over 6 days and were expressed with the absolute totals with range. No subscales were used. Cumulative scores represent the absolute sum of each data point for 6 days. The total cumulative range for nausea is 0-60. | Posted | Median | Inter-Quartile Range | Score on a scale | Cumulative every day after 6 days post-operative |
|
|
|
| Secondary | Amount of Itching Experienced | Itching as measured by a 0-10 Visual Analog Scale (VAS) itching scale, where "0" is the lowest score and "10" is the highest score. For example, 10 would be severe itching and 0 would be none. Cumulative scores were the total scores over 6 days and were expressed with the absolute totals with range. No subscales were used. Cumulative scores represent the absolute sum of each data point for 6 days. The total cumulative range for itching is 0-60. | Posted | Median | Inter-Quartile Range | Score on a scale | Cumulative every day after 6 days post-operative |
|
|
|
| Secondary | Amount of Oxycodone Used | Oxycodone use, measured by number of 5-mg tablets as standard dose | Posted | Median | Inter-Quartile Range | tablets | Cumulative every day after 6 days post-operative |
|
|
|
| 0 |
| 50 |
| 0 |
| 50 |
| 0 |
| 50 |
| EG001 | Control | 7 day supply of Percocet (oxycodone 5mg/acetaminophen 325 mg) to be taken 1-2 by mouth every 4 hours as needed for pain. Percocet: Percocet (oxycodone 5mg/acetaminophen 325 mg) | 0 | 49 | 0 | 49 | 0 | 49 |
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| D001555 |
| Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011720 | Pyrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D000083 | Acetanilides |
| D000813 | Anilides |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D005680 | gamma-Aminobutyric Acid |
| D000613 | Aminobutyrates |
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D003061 | Codeine |
| D009022 | Morphine Derivatives |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |