Clinical trial NCT04813991: Pain Control Without Opioids
Official title: Achieving Peri-Operative Pain Control Without Opioids
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Perioperative Pain
Keywords: Opioid Analgesic
Ibuprofen
Pain control
Acetaminophen
Laparoscopic Cholescystectomy
Laparoscopic Appendectomy
Lead sponsor: Hackensack Meridian Health
Sponsor class: OTHER
First posted: 2021-03-24
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized Double-Blind Intervention Trial
Primary purpose: TREATMENT

Brief summary: Adequate outpatient pain control after uncomplicated laparoscopic appendectomy or cholecystectomy can be achieved with minimal breakthrough drugs when used in combination with around the clock non-opioid medications.

Detailed description: Death from opioid overdose is now considered a national emergency. Prescribing of narcotics by physicians, particularly in the perioperative period, remains a significant contributor to opioid addiction. There is a critical need to identify post-operative pain control alternatives that eliminate narcotic usage. Without such information, clinicians will continue to rely on opioids to manage their patients' pain. Prior work supports the notion that there is little difference between the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) and that of opioid analgesics in controlling pain following surgical procedures. Recent clinical trials have concluded that a combination of centrally and peripherally acting analgesics improves patients' satisfaction and pain control. Clinical investigators have focused upon limiting opioid use rather than on eliminating the administration of narcotics. not surprisingly, there are no established evidenced-based guidelines for postoperative outpatient non-opioid pain control. The majority of U.S. surgeons continue to rely on opioids as the sole outpatient pain regimen, as suggested by a number of current guidelines.

Our observation is that adequate outpatient pain control after uncomplicated laparoscopic appendectomy or cholecystectomy can be achieved with minimal breakthrough drugs when used in combination with around the clock non-opioid medications.

The amount of opioids prescribed at discharge after laparoscopic appendectomies and cholecystectomies is quite variable. An average prescription is for 200-350 Oral Morphine Equivalents (OME) or 26-46 tabs of 5mg oxycodone with the lowest amount reported of 150 OME (20 tabs of 5mg oxy). One of the most conservative guidelines, the Michigan Surgical Quality Collaborative, recommends prescription of 75 OME after laparoscopic cholecystectomy

AIMS AND OBJECTIVES.

1. Characterize the need for breakthrough pain medication in a cohort of post-operative subjects treated utilizing a 3-day pain regimen consisting of ibuprofen and acetaminophen for postoperative outpatient pain control without the use of opioids.
2. Test the non-inferiority of a regimen consisting of ibuprofen when prescribed on as needed basis in controlling breakthrough pain compared with a regimen using oxycodone.

HYPOTHESIS

We predict that a non-opioid regimen can safely control post-operative pain as effectively as management protocols which include narcotics.

At the completion of the proposed research, our expected outcomes are to demonstrate that the ibuprofen/acetaminophen regimen provides adequate pain relief in patients who undergo uncomplicated laparoscopic cholecystectomy and appendectomy.

We also expect to have demonstrated that when breakthrough pain occurs, non-narcotic medications are as effective as opioids. These findings will be relevant to some 10 million surgeries per year in the U.S. where the patients may never need opioid exposure.

STUDY DESIGN/METHOLOGY

In this single-center, randomized, double-blind intervention trial, adult subjects will be enrolled after routine uncomplicated laparoscopic appendectomy or cholecystectomy for the management of outpatient pain. All participants will provide written informed consent.

All subjects will receive two oral analgesic medications (ibuprofen 600mg and acetaminophen 500mg) three times per day with meals, to consume for three days following discharge from the hospital. For breakthrough pain, with a double-blind approach with opaque capsules for the medications, subjects will be randomized to receive five packages of two pills containing either ibuprofen 600mg (Arm 1) or oxycodone 5mg(Arm 2). They will be instructed to consume breakthrough medications no more than twice per day.

The subjects will maintain a pain log and will record their pain intensity prior to meals each day, and also the maximum pain intensity for the given day, using a verbal pain Numerical Rating Scale (NRS) that ranges from 0 to 10.

A research team member will contact each subject daily by phone for seven days and confirm the subject is consuming their medications and collect information regarding pain intensity.

Subjects will be asked the following questions:

* To rate their pain on a scale of 0 to 10 daily, average and maximum.
* To report the # of breakthrough pain medication pills taken that day and how many total remain

If the subject reports a pain score of 8 or greater after taking the both breakthrough medications during a 24 hour period, they will be considered a study failure. Patient will be told to contact their surgeon for follow up. The research coordinator will follow up these subjects to confirm they have spoken to their treating physician.

Eligibility criteria: Inclusion Criteria:

* Ages 18-90
* English or Spanish speaking
* Undergoing routine laparoscopic appendectomy or cholecystectomy
* Able to provide Informed Consent

Exclusion Criteria:

* Current use of methadone
* Opioid use within 30 days prior to hospitalization
* Actively taking anti-inflammatory medications
* History of Adverse Reactions to Study Medications
* Pregnancy
* Currently Breastfeeding
* Ongoing treatment for Peptic Ulcer Disease
* Hepatitis, cirrhosis, severe liver dysfunction (elevated MELD score or LFT's \> twice the upper limit of normal.)
* Renal dysfunction with a creatinine more than 25% above age normal values.
* Taking any medicine that might interact with one of the study medications such as SSRI's or Tricyclics, anti-psychotics, anti-malaria medications quinidine or halofantrine, Amiodarone or Dronedarone, diphenhydramine, celecoxib, ranitidine, cimetidine, ritanovir, terbinafine, or St John's Wort

The subject will be withdrawn from the study prior to any randomization if the following occurs:

* Conversion from laparoscopic to open procedure
* Subject does not undergo any operation;
* Subject has a complicated hospital course requiring prolonged hospitalization; subject experiences post-operative complications.

Primary outcomes:
measure: Incidence of Breakthrough Pain
timeFrame: 7 Days
Secondary outcomes:
measure: Time-weighted average daily pain score over first three days post-discharge.
timeFrame: 3 Days
Other outcomes:
Locations:
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
Study officials:
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