Opioid UsePhase 4NCT04015908
A Multimodal Analgesia Protocol Adapted for Ambulatory Surgery
A Phase 4 study testing Celecoxib, Acetaminophen and Pregabalin in people with Opioid Use, run by University of Utah at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Opioid Use
- What is being tested?
- Celecoxib, Acetaminophen and Pregabalin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2019to 31 Jan 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients between the ages of 18 and 65 having one of three elective procedures as an outpatient. These procedures are associated with moderate to severe postoperative pain (anterior cruciate ligament reconstruction (knee), ankle ligament reconstruction (foot/ankle), or ligament reconstruction with tendon interposition (hand))
- Patients should have operative risk category of American Society of Anesthesiologists (ASA) 1 or 2 .
- Patients weighing between 70-100kg will be included to allow standardization of medication dosing
Who cannot join
- Allergy to Study Medications
- Previous History of Chronic Opioid Use
- Patient Refusal to Participate
- Known of Suspected History of Sleep Apnea
- Known History of Chronic Pain Syndrome
- Weight less than 70kg or greater than 100kg due to standardization of medication doses.
Show all 10Show fewer
- Revision Surgery
- Inability to take study medications due to medication incompatibility or co-existing disease
- Patients refusing or unable to receive US guided nerve block for postoperative pain
- Patients unable to read and comprehend written consent document
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
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:
- Three non-opioid pain medications (acetaminophen,celecoxib, and pregabalin) would be taken concurrently at six hour intervals for a period of 7 days.
- These three non-opioid medications (acetaminophen, celecoxib, and pregabalin ) would be provided in a "blister pack". All scheduled pain medication for a given 6 hour interval would be contained in a single compartment to simplify compliance for the patient. Study patients would also have access to oxycodone as a "rescue medication".
The principles of postoperative pain management addressed in this protocol are supported by existing literature.
- Patient compliance with complex medication dosing protocols may be improved using calender and time based "blister packs".
- Pain control using combined acetaminophen and NSAID is superior to that either drug in isolation
- Pregabalin can reduce opioid requirements and opioid related nausea when treating acute pain.
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.
- Conditions
- Opioid Use
- Being tested
- Celecoxib, Acetaminophen, Pregabalin, Oxycodone, Percocet
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CelecoxibDrug
Also called Celebrex
Celecoxib 100mg
AcetaminophenDrug
Also called Paracetamol
Acetaminophen 325mg
PregabalinDrug
Also called Lyrica
Pregabalin 50 mg
OxycodoneDrug
Also called Xtampza ER, Oxaydo, Roxicodone
oxycodone 5-10 mg
PercocetDrug
Also called Oxycodone / Paracetamol
Percocet (oxycodone 5mg/acetaminophen 325 mg)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Celecoxib; Drug: Acetaminophen; Drug: Pregabalin; Drug: Oxycodone |
| 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. Receives: Drug: Percocet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Cumulative every day after 6 days post-operative
Secondary outcomes (3)
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.
Measured: 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.
Measured: Cumulative every day after 6 days post-operative
Amount of Oxycodone Used
Oxycodone use, measured by number of 5-mg tablets as standard dose
Measured: Cumulative every day after 6 days post-operative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2019
- Study start1 Aug 2019
- Primary completion31 Jan 2023
- Study completion31 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Opioid UseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeffrey Swenson, MS, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04015908
- Sponsor's protocol ID
- 121505
- Status last verified
- May 2024
- First submitted
- 4 Jul 2019
- Last updated
- 8 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36518729
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multimodal Analgesia Protocol Adapted for Ambulatory Surgery
- ClinicalTrials.gov ID
- NCT04015908
- Acronym / sponsor ID
- 121505
- Conditions
- Opioid Use
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- 1 Aug 2019 (actual)
- Primary completion
- 31 Jan 2023 (actual)
- Study completion
- 31 Jan 2023 (actual)
- First posted
- 11 Jul 2019 (actual)
- Results
- Posted 8 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- Three non-opioid pain medications (acetaminophen,celecoxib, and pregabalin) would be taken concurrently at six hour intervals for a period of 7 days.
- These three non-opioid medications (acetaminophen, celecoxib, and pregabalin ) would be provided in a "blister pack". All scheduled pain medication for a given 6 hour interval would be contained in a single compartment to simplify compliance for the patient. Study patients would also have access to oxycodone as a "rescue medication".
The principles of postoperative pain management addressed in this protocol are supported by existing literature.
- Patient compliance with complex medication dosing protocols may be improved using calender and time based "blister packs".
- Pain control using combined acetaminophen and NSAID is superior to that either drug in isolation
- Pregabalin can reduce opioid requirements and opioid related nausea when treating acute pain.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| multi-modal | Experimental | Drug: Celecoxib, Drug: Acetaminophen, Drug: Pregabalin, Drug: Oxycodone3 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 | Drug: Percocet7 day supply of Percocet (oxycodone 5mg/acetaminophen 325 mg) to be taken 1-2 by mouth every 4 hours as needed for pain. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- All patients between the ages of 18 and 65 having one of three elective procedures as an outpatient. These procedures are associated with moderate to severe postoperative pain (anterior cruciate ligament reconstruction (knee), ankle ligament reconstruction (foot/ankle), or ligament reconstruction with tendon interposition (hand))
- Patients should have operative risk category of American Society of Anesthesiologists (ASA) 1 or 2 .
- Patients weighing between 70-100kg will be included to allow standardization of medication dosing
Key exclusion criteria (10 listed)
- Allergy to Study Medications
- Previous History of Chronic Opioid Use
- Patient Refusal to Participate
- Known of Suspected History of Sleep Apnea
- Known History of Chronic Pain Syndrome
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CelecoxibAlso: CelebrexCelecoxib 100mg | Drug | multi-modal |
| AcetaminophenAlso: ParacetamolAcetaminophen 325mg | Drug | multi-modal |
| PregabalinAlso: LyricaPregabalin 50 mg | Drug | multi-modal |
| OxycodoneAlso: Xtampza ER, Oxaydo, Roxicodoneoxycodone 5-10 mg | Drug | multi-modal |
| PercocetAlso: Oxycodone / ParacetamolPercocet (oxycodone 5mg/acetaminophen 325 mg) | Drug | Control |
Primary outcome
Amount of Pain Experienced
Time frame: Cumulative every day after 6 days post-operative
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.
3 secondary outcomes
Amount of Nausea Experienced
Time frame: Cumulative every day after 6 days post-operative
Amount of Itching Experienced
Time frame: Cumulative every day after 6 days post-operative
Amount of Oxycodone Used
Time frame: Cumulative every day after 6 days post-operative
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36518729Swenson 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Swenson, MS principal investigator
University of Utah
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Celecoxib, Acetaminophen and Pregabalin in people with Opioid Use, run by University of Utah at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Amount of Pain Experienced (time frame: Cumulative every day after 6 days post-operative). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04015908, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2024; AzTrials last refreshed its copy on 30 Oct 2026.