A Multimodal Analgesia Protocol Adapted for Ambulatory Surgery

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 Overview

• Status: Completed
• Conditions: Opioid Use
• Intervention / Treatment: Drug: Celecoxib; Drug: Acetaminophen; Drug: Pregabalin; Drug: Oxycodone; Drug: Percocet

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Celecoxib; Celecoxib 100mg; Other Names: Celebrex; Drug: Acetaminophen; Acetaminophen 325mg; Other Names: Paracetamol; Drug: Pregabalin; Pregabalin 50 mg; Other Names: Lyrica; Drug: Oxycodone; oxycodone 5-10 mg; Other Names: Xtampza ER, Oxaydo, Roxicodone
Active Comparator: 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.	Drug: Percocet; Percocet (oxycodone 5mg/acetaminophen 325 mg); Other Names: Oxycodone / Paracetamol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of Pain experienced	Pain as measured by a 0-10 Visual Analog Scale (VAS) pain scale	Directly after waking every morning for 7 days post-operative
Amount of Pain experienced	Pain as measured by a 0-10 Visual Analog Scale (VAS) pain scale	Directly before going to sleep each night for 7 days post-operative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of Nausea experienced	Nausea as measured by a 0-11 VAS nausea scale	Directly after waking every morning for 7 days post-operative
Amount of Itching experienced	Itching as measured by a 0-11 VAS nausea scale	Directly after waking every morning for 7 days post-operative
Amount of Nausea experienced	Nausea as measured by a 0-11 VAS nausea scale	Directly before going to sleep each night for 7 days post-operative
Amount of Itching experienced	Itching as measured by a 0-11 VAS nausea scale	Directly before going to sleep each night for 7 days post-operative

Collaborators and Investigators

• Sponsor: University of Utah
• Investigators: Principal Investigator: Jeffrey Swenson, MS, University of Utah

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Actual): January 31, 2023
• Study Completion (Actual): January 31, 2023

Study Registration Dates

• First Submitted: July 4, 2019
• First Submitted That Met QC Criteria: July 10, 2019
• First Posted (Actual): July 11, 2019

Study Record Updates

• Last Update Posted (Actual): July 20, 2023
• Last Update Submitted That Met QC Criteria: July 19, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Cyclooxygenase 2 Inhibitors; Calcium Channel Blockers; Celecoxib; Acetaminophen; Pregabalin; Oxycodone
• Other Study ID Numbers: 121505

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes