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 (Actual): 1815
• Phase: Phase 3

Contacts and Locations

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
Pain Worst 1	Participants are asked to rate the worst pain they experienced during the day (recorded before going to sleep) and overnight (recorded when waking up) on a NRS scale of 0 to 10 where 0=no pain and 10=pain as bad as you can imagine. Pain Worst 1 is the average of the ratings provided at the end of day of surgery (day 1) and when waking up the next morning (1 night after surgery).	End of day of surgery (day 1) and when waking up the next morning (1 night after surgery)
Pain Worst 2	Participants are asked to rate the worst pain they experienced during the day (recorded before going to sleep) and overnight (recorded when waking up) on a NRS scale of 0 to 10 where 0=no pain and 10=pain as bad as you can imagine. Pain Worst 2 is the average of the ratings provided at the end of day of after surgery (day 2) and when waking up the next morning (2nd night after surgery.)	End of day of after surgery (day 2) and when waking up the next morning (2nd night after surgery
Pain Worst 3	Participants are asked to rate the worst pain they experienced during the day (recorded before going to sleep) and overnight (recorded when waking up) on a NRS scale of 0 to 10 where 0=no pain and 10=pain as bad as you can imagine. Pain Worst 3 is the average of the ratings provided at the end of 2nd day of after surgery (day 3) and when waking up the next morning (3rd night after surgery).	End of 2nd day of after surgery (day 3) and when waking up the next morning (3rd night after surgery)
Pain Worst All	Participants are asked to rate the worst pain they experienced during the day (recorded before going to sleep) and overnight (recorded when waking up) on a NRS scale of 0 to 10 where 0=no pain and 10=pain as bad as you can imagine. Pain Worst all is the average of the ratings provided at the end of first 7 days after surgery (days 1 thru 7) and when waking up the first 7 mornings (1st thru 7th nights after surgery).	End of first 7 days after surgery (days 1 thru 7) and when waking up the first 7 mornings (1st thru 7th nights after surgery)
Pain Average 1	Participants are asked to rate the average pain they experienced during the day (recorded before going to sleep) and overnight (recorded when waking up) on a NRS scale of 0 to 10 where 0=no pain and 10=pain as bad as you can imagine. Pain Average 1 is the average of the ratings provided at the end of day of surgery (day 1) and when waking up the next morning (1 night after surgery)	End of day of surgery (day 1) and when waking up the next morning (1 night after surgery)
Pain Average 2	Participants are asked to rate the average pain they experienced during the day (recorded before going to sleep) and overnight (recorded when waking up) on a NRS scale of 0 to 10 where 0=no pain and 10=pain as bad as you can imagine. Pain Average 2 is the average of the ratings provided at the end of day of after surgery (day 2) and when waking up the next morning (2nd night after surgery.)	End of day of after surgery (day 2) and when waking up the next morning (2nd night after surgery)
Pain Average 3	Participants are asked to rate the average pain they experienced during the day (recorded before going to sleep) and overnight (recorded when waking up) on a NRS scale of 0 to 10 where 0=no pain and 10=pain as bad as you can imagine. Pain Average 3 is the average of the ratings provided at the end of 2nd day of after surgery (day 3) and when waking up the next morning (3rd night after surgery).	End of 2nd day of after surgery (day 3) and when waking up the next morning (3rd night after surgery)
Pain Average All	Participants are asked to rate the average pain they experienced during the day (recorded before going to sleep) and overnight (recorded when waking up) on a NRS scale of 0 to 10 where 0=no pain and 10=pain as bad as you can imagine. Pain Average all is the average of the ratings provided at the end of first 7 days after surgery (days 1 thru 7) and when waking up the first 7 mornings (1st thru 7th nights after surgery).	End of first 7 days after surgery (days 1 thru 7) and when waking up the first 7 mornings (1st thru 7th nights after surgery)
Overall Satisfaction	Participant rating on a five point Likert Scale (1=very satisfied, 2=satisfied, 3=neither satisfied or dissatisfied, 4=dissatisfied, 5=very dissatisfied) to the question: "Overall, how satisfied were you with your current pain medication?"	At time of post-operative visit (day 9 +/- 5 days)
Composite Pain 1	Before going to sleep participants are asked to rate their "worst pain experienced", "least pain experienced" and "average pain experienced" during the day along with "pain now." Upon waking participants were asked to rate their "worst pain experienced", "least pain experienced" and "average pain experienced" during the night along with "pain now." A NRS scale of 0 to 10 where 0=no pain and 10=pain as bad as you can imagine was used. Composite Pain 1 is the average of all ratings provided at the end of day of surgery (day 1) and when waking up the next morning (1 night after surgery).	End of day of surgery (day 1) and when waking up the next morning (1 night after surgery)
Composite Pain 2	Before going to sleep participants are asked to rate their "worst pain experienced", "least pain experienced" and "average pain experienced" during the day along with "pain now." Upon waking participants were asked to rate their "worst pain experienced", "least pain experienced" and "average pain experienced" during the night along with "pain now." A NRS scale of 0 to 10 where 0=no pain and 10=pain as bad as you can imagine was used. Composite Pain 2 is the average of all ratings provided day after surgery (day 2) and when waking up the next morning (2nd night after surgery).	End of day of the second day after surgery (day 2) and when waking up the next morning (2nd night after surgery)
Composite Pain 3	Before going to sleep participants are asked to rate their "worst pain experienced", "least pain experienced" and "average pain experienced" during the day along with "pain now." Upon waking participants were asked to rate their "worst pain experienced", "least pain experienced" and "average pain experienced" during the night along with "pain now." A NRS scale of 0 to 10 where 0=no pain and 10=pain as bad as you can imagine was used. Composite Pain 3 is the average of all ratings provided two days after surgery (day 3) and when waking up the 3rd morning after surgery (3rd night after surgery).	End of day of the third day after surgery (day 3) and when waking up the next morning (3rd night after surgery)
Composite Pain All	Before going to sleep participants are asked to rate their "worst pain experienced", "least pain experienced" and "average pain experienced" during the day along with "pain now." Upon waking participants were asked to rate their "worst pain experienced", "least pain experienced" and "average pain experienced" during the night along with "pain now." A NRS scale of 0 to 10 where 0=no pain and 10=pain as bad as you can imagine was used. Composite Pain All is the average of the ratings provided at the end of first 7 days after surgery (days 1 thru 7) and when waking up the first 7 mornings (1st thru 7th nights after surgery).	End of first 7 days after surgery (days 1 thru 7) and when waking up the first 7 mornings (1st thru 7th nights after surgery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Receiving Rescue Medication	Participant receiving additional pain medication (oxycodone) as study analgesic is not managing pain sufficiently	At post operative visit (9 days after surgery +/- 5 days)
Pain Interference 1	Participants were asked to rate, on a 5 point Likert Scale, how much did pain interfered with their 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} Pain Interference 1 is the average ratings provided at the end of the day of surgery. Lower scores are better.	End of the day of surgery (day 1)
Pain Interference 2	Participants were asked to rate, on a 5 point Likert Scale, how much did pain interfered with their 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} Pain Interference 2 is the average ratings provided at the end of day after surgery (day 2). Lower scores are better.	End of the first full day after surgery (day 2)
Pain Interference 3	Participants were asked to rate, on a 5 point Likert Scale, how much did pain interfered with their 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} Pain Interference 3 is the average ratings provided at the end of 2nd day after surgery (day 3). Lower scores are better.	End of the second full day after surgery (day 3)
Pain Interference All	Participants were asked to rate, on a 5 point Likert Scale, how much did pain interfered with their 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} Pain Interference ALL is the average ratings provided at the end of the 1st seven days after surgery (days 1 thru 7). Lower scores are better.	First 7 days after surgery
Sleep 1	Participants were asked to rate the overall quality of their sleep the 1st night after surgery on a NRS scale of 0 to 10 where 0=excellent and 10=very poor. Sleep 1 is the rating provided when first waking up the day after surgery.	When first waking up the day after surgery
Sleep 2	Participants were asked to rate the overall quality of their sleep the 2nd night after surgery on a NRS scale of 0 to 10 where 0=excellent and 10=very poor. Sleep 2 is the rating provided when first waking up the second day after surgery.	When first waking up the 2nd day after surgery
Sleep 3	Participants were asked to rate the overall quality of their sleep the 3rd night after surgery on a NRS scale of 0 to 10 where 0=excellent and 10=very poor. Sleep 1 is the rating provided when first waking up the third day after surgery.	When first waking up the 3rd day after surgery
Sleep All	Participants were asked to rate the overall quality of their sleep for the first 7 nights after surgery on a NRS scale of 0 to 10 where 0=excellent and 10=very poor. Sleep All is the average rating provided for all seven nights.	First 7 nights after surgery
Potential for Opioid Tablet Diversion	Number of returned opioid 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.
• Feldman CA, Fredericks-Younger J, Desjardins PJ, Malmstrom H, Miloro M, Warburton G, Ward BB, Ziccardi VB, Greenberg P, Andrews T, Matheson PB, Benoliel R, Fine DH, Lu SE. Nonopioid vs opioid analgesics after impacted third-molar extractions: The Opioid Analgesic Reduction Study randomized clinical trial. J Am Dent Assoc. 2025 Feb;156(2):110-123.e9. doi: 10.1016/j.adaj.2024.10.014. Epub 2025 Jan 4.

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2021
• Primary Completion (Actual): July 7, 2023
• Study Completion (Estimated): July 31, 2026

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): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

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: Narcotic-Related Disorders; Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Neurobehavioral Manifestations; Substance-Related Disorders; Chemically-Induced Disorders; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Opioid-Related Disorders; Agnosia; Personal Satisfaction; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Analgesics
• Other Study ID Numbers: Pro2020002299; 5UH3DE028860-05 (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