A Multimodal Analgesia Protocol Adapted for Ambulatory Surgery

NCT ID: NCT04015908

Last Updated: 2024-07-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-01
• Study Completion Date: 2023-01-31

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.

Conditions

Opioid Use

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Celecoxib

Intervention Type: DRUG

Celecoxib 100mg

Acetaminophen

Intervention Type: DRUG

Acetaminophen 325mg

Pregabalin

Intervention Type: DRUG

Pregabalin 50 mg

Oxycodone

Intervention Type: DRUG

oxycodone 5-10 mg

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.

Group Type: ACTIVE_COMPARATOR

Percocet

Intervention Type: DRUG

Percocet (oxycodone 5mg/acetaminophen 325 mg)

Interventions

Celecoxib

Celecoxib 100mg

Intervention Type: DRUG

Acetaminophen

Acetaminophen 325mg

Intervention Type: DRUG

Pregabalin

Pregabalin 50 mg

Intervention Type: DRUG

Oxycodone

oxycodone 5-10 mg

Intervention Type: DRUG

Percocet

Percocet (oxycodone 5mg/acetaminophen 325 mg)

Intervention Type: DRUG

Other Intervention Names

Celebrex; Paracetamol; Lyrica; Xtampza ER, Oxaydo, Roxicodone; Oxycodone / Paracetamol

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Utah

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey Swenson, MS

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

University of Utah

Salt Lake City, Utah, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 36518729 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

121505

Identifier Type: -

Identifier Source: org_study_id