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A Multimodal Analgesia Protocol Adapted for Ambulatory Surgery

A Multimodal Analgesia Protocol Adapted for Ambulatory Surgery

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04015908
Enrollment
100
Registered
2019-07-11
Start date
2019-08-01
Completion date
2023-01-31
Last updated
2024-07-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Opioid Use

Brief 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. 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. 1. Patient compliance with complex medication dosing protocols may be improved using calender and time based blister packs. 2. Pain control using combined acetaminophen and NSAID is superior to that either drug in isolation 3. 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.

Interventions

DRUGCelecoxib

Celecoxib 100mg

DRUGAcetaminophen

Acetaminophen 325mg

DRUGPregabalin

Pregabalin 50 mg

DRUGOxycodone

oxycodone 5-10 mg

Percocet (oxycodone 5mg/acetaminophen 325 mg)

Sponsors

University of Utah
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No

Inclusion criteria

* 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

Exclusion criteria

* 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. * 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

Design outcomes

Primary

MeasureTime frameDescription
Amount of Pain ExperiencedCumulative every day after 6 days post-operativePain 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.

Secondary

MeasureTime frameDescription
Amount of Nausea ExperiencedCumulative every day after 6 days post-operativeNausea 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.
Amount of Itching ExperiencedCumulative every day after 6 days post-operativeItching 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.
Amount of Oxycodone UsedCumulative every day after 6 days post-operativeOxycodone use, measured by number of 5-mg tablets as standard dose

Countries

United States

Participant flow

Participants by arm

ArmCount
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
50
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)
50
Total100

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyLost to Follow-up01

Baseline characteristics

CharacteristicMulti-modalControlTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
50 Participants50 Participants100 Participants
Age, Continuous32 years
STANDARD_DEVIATION 11
37 years
STANDARD_DEVIATION 11
35 years
STANDARD_DEVIATION 11
Body mass index26 kg/m^2
STANDARD_DEVIATION 6
27 kg/m^2
STANDARD_DEVIATION 4
27 kg/m^2
STANDARD_DEVIATION 5
Height169 cm
STANDARD_DEVIATION 9
171 cm
STANDARD_DEVIATION 8
170 cm
STANDARD_DEVIATION 9
Intraoperative fentanyl110 mg
STANDARD_DEVIATION 45
110 mg
STANDARD_DEVIATION 46
110 mg
STANDARD_DEVIATION 45
PACU fentanyl93 mg
STANDARD_DEVIATION 66
92 mg
STANDARD_DEVIATION 77
93 mg
STANDARD_DEVIATION 72
Race and Ethnicity Not Collected0 Participants
Scopolamine patch19 Participants19 Participants38 Participants
Sex: Female, Male
Female
37 Participants32 Participants69 Participants
Sex: Female, Male
Male
13 Participants18 Participants31 Participants
Weight75 kg
STANDARD_DEVIATION 13
80 kg
STANDARD_DEVIATION 13
76 kg
STANDARD_DEVIATION 13

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 500 / 49
other
Total, other adverse events
0 / 500 / 49
serious
Total, serious adverse events
0 / 500 / 49

Outcome results

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.

Time frame: Cumulative every day after 6 days post-operative

ArmMeasureValue (MEDIAN)
Multi-modalAmount of Pain Experienced28 Score on a scale
ControlAmount of Pain Experienced35 Score on a scale
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.

Time frame: Cumulative every day after 6 days post-operative

ArmMeasureValue (MEDIAN)
Multi-modalAmount of Itching Experienced0 Score on a scale
ControlAmount of Itching Experienced0 Score on a scale
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.

Time frame: Cumulative every day after 6 days post-operative

ArmMeasureValue (MEDIAN)
Multi-modalAmount of Nausea Experienced0 Score on a scale
ControlAmount of Nausea Experienced0 Score on a scale
Secondary

Amount of Oxycodone Used

Oxycodone use, measured by number of 5-mg tablets as standard dose

Time frame: Cumulative every day after 6 days post-operative

ArmMeasureValue (MEDIAN)
Multi-modalAmount of Oxycodone Used0 tablets
ControlAmount of Oxycodone Used8 tablets

Source: ClinicalTrials.gov · Data processed: Feb 10, 2026