Opioid Analgesic Reduction Study (OARS)

Opioid Analgesic Reduction Study (OARS): Managing Acute Post-Operative Surgical Pain

The goal is to provide health care professionals, including dentists, with the best possible evidence for clinical decision making when deciding upon analgesics for acute post-surgical pain management, a double-blind, stratified randomized clinical trial will be conducted to test the hypothesis that a combination of over-the-counter non-opioid containing analgesics is at least as, if not more, effective (non-inferior) than the most commonly prescribed opioid analgesic. The impacted 3rd molar extraction model will be used due to the predictable severity of the post-operative pain and generalizability of results.

This double-blind, prospective, stratified, randomized pragmatic clinical trial will use the impacted 3rd molar extraction pain model.

Study Overview

• Status: Active, not recruiting
• Conditions: Opioid Use
• Intervention / Treatment: Drug: opioid-containing analgesic; Drug: two over-the-counter analgesics

• Study Type: Interventional
• Enrollment (Estimated): 1800
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Julie Chapman-Greene, PhD; Phone Number: 973-972-3620; Email: chapmaje@sdm.rutgers.edu
• Study Contact Backup: Name: Janine Fredericks-Younger, DMD; Phone Number: 973-972-1679; Email: frederja@sdm.rutgers.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • New Jersey
    • Newark, New Jersey, United States, 07101
      • Rutgers School of Dental Medicine
  • New York
    • Rochester, New York, United States, 14620
      • University of Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

An individual must meet all of the following criteria to be eligible to participate in the study:

• Be able to understand the informed consent.
• Provide signed and dated informed consent form
• Be able to understand all directions for data gathering instruments in English
• Be willing and able to comply with all study procedures and be available for the duration of the study
• Planning to undergo extraction of one or more partial or fully impacted mandibular 3rd molars
• Be 18 years or older
• Be in good general health as evidenced by medical history

• Women must agree to use one of the following methods of contraception while participating in this study:

  • contraceptive pill
  • intra-uterine device
  • condoms
  • abstinence

Exclusion Criteria:

Participants who self-report the following history will be excluded from participating:

• History of gastrointestinal bleeding and/or peptic ulcer
• History of renal disease (excluding kidney stones)
• History of hepatic disease
• History of bleeding disorder
• History of respiratory depression
• Any prior respiratory effect of an opioid or other anesthetic drugs that required respiratory support postoperatively
• Active or untreated asthma
• History of known allegoric reaction to ibuprofen, acetaminophen, hydrocodone, and/or anesthesia

• Currently taking any of the following medications:

  • CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), which may increase plasma concentrations of hydrocodone bitartrate and acetaminophen and prolong opioid adverse reactions, and which may cause potentially fatal respiratory depression
  • CNS depressants.
• Consumes 3 or more alcoholic drinks every day and/or has a history of alcoholism
• History of drug or alcohol abuse
• Family history of drug or alcohol abuse in a first-degree relative
• Has had no more than one opioid prescription filled within the past 12 months
• Currently pregnant or lactating

Participants would also be excluded due to any additional criteria that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study which includes:

• Prior participation in this study
• Inability or refusal to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Opioid; Combination analgesic of hydrocodone 5mg/acetaminophen 300 mg and a placebo pill.	Drug: opioid-containing analgesic; hydrocodone/ acetaminophen combination product
Active Comparator: Non-Opioid; Combination of ibuprofen 400 mg/acetaminophen 500 mg	Drug: two over-the-counter analgesics; combination of over-the-counter analgesics (ibuprofen/acetaminophen)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brief Pain Inventory pain scale using Numeric Rating Scale	Mean score (scale of 0 to 10, 0=no pain, 10=worst imaginable pain)	the first 24 hours post surgery
Brief Pain Inventory pain scale using Numeric Rating Scale	Mean score (scale of 0 to 10, 0=no pain, 10=worst imaginable pain)	the first 48 hours post surgery
Brief Pain Inventory pain scale using Numeric Rating Scale	Mean score (scale of 0 to 10, 0=no pain, 10=worst imaginable pain)	the first 7 days post surgery
PTSS satisfaction questions assessing overall satisfaction	How satisfied are you with the TIME that it takes your pain medication to work? (5 pt. scale: 1=very satisfied, 5=very dissatisfied); How satisfied are you with the LEVEL OF AMOUNT of pain relief provided by your pain medication? (5 pt. scale: 1=very satisfied, 5=very dissatisfied); How satisfied are you with the DURATION of pain relief provided by your pain medication? (5 pt. scale: 1=very satisfied, 5=very dissatisfied); Overall, how satisfied are you with your pain medication? (5 pt. scale: 1=very satisfied, 5=very dissatisfied); Overall, how does your level of pain relief meet you expectations of pain relief? (5 pt. scale: 1=greatly exceeds my expectations, 5=does not meet my expectations at all); Do you think that your pain medication could be more effective in relieving your pain? (5 pt. scale: 1=yes, definitely, 5=definitely not)	At post operative visit (9 days after surgery +/- 5 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events experienced	Total adverse events experienced (count of yes answers to excessive fatigue or drowsiness, inability to concentrate, nausea, diarrhea, dizziness, constipation, skin rashes, stomach aches, heartburn, vomiting, euphoria, headache, urinary retention and unintentional weight gain)	Total events recorded each morning and evening after surgery for the first 24 hours post surgery
Adverse events experienced	Total adverse events experienced (count of yes answers to excessive fatigue or drowsiness, inability to concentrate, nausea, diarrhea, dizziness, constipation, skin rashes, stomach aches, heartburn, vomiting, euphoria, headache, urinary retention and unintentional weight gain)	Total events recorded each morning and evening after surgery for the first 48 hours post surgery
Adverse events experienced	Total adverse events experienced (count of yes answers to excessive fatigue or drowsiness, inability to concentrate, nausea, diarrhea, dizziness, constipation, skin rashes, stomach aches, heartburn, vomiting, euphoria, headache, urinary retention and unintentional weight gain)	Total events recorded each morning and evening for the first 7 days post surgery
Pain interference (daily function)	Mean score of Patient-Reported Outcomes Measurement Information System questions related to pain interference: During the post-operative period, how much did pain interfere with your day to day activities, work around the home, ability to participate in social activities, enjoyment of life, the things you usually do for fun, enjoyment of social activities, household chores, family life, your ability to concentrate, enjoyment of recreational activities, tasks away from home {scale: 1=not at all, 2=a little bit, 3=somewhat, 4=quite a bit, 5=very much} and How often did pain keep you from socializing with others? {scale=1=never, 2=rarely, 3=sometimes, 4=often, 5=always}	Day 2 post surgery (recorded the evening of day 2)
Pain interference (daily function)	Mean score of Patient-Reported Outcomes Measurement Information System questions related to pain interference: During the post-operative period, how much did pain interfere with your day to day activities, work around the home, ability to participate in social activities, enjoyment of life, the things you usually do for fun, enjoyment of social activities, household chores, family life, your ability to concentrate, enjoyment of recreational activities, tasks away from home {scale: 1=not at all, 2=a little bit, 3=somewhat, 4=quite a bit, 5=very much} and How often did pain keep you from socializing with others? {scale=1=never, 2=rarely, 3=sometimes, 4=often, 5=always}	Days 2 and 3 post surgery (recorded the evenings of days 2 and 3)
Pain interference (daily function)	Mean score of Patient-Reported Outcomes Measurement Information System questions related to pain interference: During the post-operative period, how much did pain interfere with your day to day activities, work around the home, ability to participate in social activities, enjoyment of life, the things you usually do for fun, enjoyment of social activities, household chores, family life, your ability to concentrate, enjoyment of recreational activities, tasks away from home {scale: 1=not at all, 2=a little bit, 3=somewhat, 4=quite a bit, 5=very much} and How often did pain keep you from socializing with others? {scale=1=never, 2=rarely, 3=sometimes, 4=often, 5=always}	First 7 days post surgery
Sleep quality (Questions from PSQ-3)	• Pain and Sleep Questionnaire three-item index : a. Last night did you have trouble falling asleep? b. Last night were you awakened by pain during the night? c. Were you awakened by pain this morning? {Binary yes/no)	For the first night post surgery
Sleep quality (Questions from PSQ-3)	• Pain and Sleep Questionnaire three-item index : a. Last night did you have trouble falling asleep? b. Last night were you awakened by pain during the night? c. Were you awakened by pain this morning? {Binary yes/no)	For the first 2 nights post surgery
Sleep Quality (Questions from PSQ-3)	• Pain and Sleep Questionnaire three-item index : a. Last night did you have trouble falling asleep? b. Last night were you awakened by pain during the night? c. Were you awakened by pain this morning? {Binary yes/no)	For the first 7 nights post surgery
Sleep Quality (PSQ-3)	• Pain and Sleep Questionnaire three-item index : a. Last night did you have trouble falling asleep? b. Last night were you awakened by pain during the night? c. Were you awakened by pain this morning? NRS scale where 0=never, 10=always	Recorded during Visit 2 (Post operative visit 9 days +/-5 days post surgery)
Overall satisfaction with sleep	NRS where 0=never, 10=always	For the first 7 evenings post surgery
Overall satisfaction with sleep	From PTSS: Rating the overall quality of last night's sleep {NRS where 0=excellent and10=very poor}	For the first 7 evenings post surgery
Potential for opioid tablet diversion	Number of returned analgesic capsules at post operative visit (9 days after surgery +/- 5 days)	At post operative visit (9 days after surgery +/- 5 days)

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: University of Maryland, Baltimore; University of Michigan; University of Illinois at Chicago; National Institute of Dental and Craniofacial Research (NIDCR); University of Rochester
• Investigators: Principal Investigator: Cecile A Feldman, DMD, Rutgers, the State University of New Jersey

Publications and helpful links

General Publications

• Feldman CA, Fredericks-Younger J, Lu SE, Desjardins PJ, Malmstrom H, Miloro M, Warburton G, Ward B, Ziccardi V, Fine D. The Opioid Analgesic Reduction Study (OARS)-a comparison of opioid vs. non-opioid combination analgesics for management of post-surgical pain: a double-blind randomized clinical trial. Trials. 2022 Feb 17;23(1):160. doi: 10.1186/s13063-022-06064-8.

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2021
• Primary Completion (Actual): December 31, 2023
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: April 7, 2020
• First Submitted That Met QC Criteria: June 29, 2020
• First Posted (Actual): June 30, 2020

Study Record Updates

• Last Update Posted (Actual): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Satisfaction; Ibuprofen; Acetaminophen; Hydrocodone; Pain Management; Opioid Addiction; Opioid Analgesics; 3rd molar extraction pain model; Opioid Diversion; Over the counter analgesics
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Analgesics
• Other Study ID Numbers: Pro2020002299; 1UG3DE028860-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Electronic Data Capture (EDC) will be used extensively throughout the course of the study for the collection of patient data as well as driving operational/logistical workflows. The database with data dictionary will be available.
• IPD Sharing Time Frame: 12 months after publication
• IPD Sharing Access Criteria: Request data access from the PI.

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.: No