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Opioid UsePhase 3OARSNCT04452344

Opioid Analgesic Reduction Study

A Phase 3 study testing opioid-containing analgesic and two over-the-counter analgesics in people with Opioid Use, run by Rutgers, The State University of New Jersey at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Opioid Use
What is being tested?
opioid-containing analgesic and two over-the-counter analgesics
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,815 participants
Where
5 sitesUnited States
Study dates
4 Jan 2021to 24 Dec 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites
  • University of Michigan

    Ann Arbor, Michigan, 48109

  • University of Maryland

    Baltimore, Maryland, 21201

  • University of Illinois at Chicago

    Chicago, Illinois, 60612

  • Rutgers School of Dental Medicine

    Newark, New Jersey, 07101

  • University of Rochester

    Rochester, New York, 14620

Other trials in United States

About this study

Official title: 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.

Conditions
Opioid Use
Being tested
opioid-containing analgesic, two over-the-counter analgesics
Keywords
3rd molar extraction pain model, Opioid Analgesics, Opioid Diversion, Over the counter analgesics, Acetaminophen, Ibuprofen, Hydrocodone, Opioid Addiction, Pain Management, Satisfaction
Medical subject headings
Opioid-Related Disorders, Agnosia, Personal Satisfaction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • opioid-containing analgesicDrug

    hydrocodone/ acetaminophen combination product

  • two over-the-counter analgesicsDrug

    combination of over-the-counter analgesics (ibuprofen/acetaminophen)

Study groups in NCT04452344
Study groupRoleWhat they receive
OpioidActive comparatorCombination analgesic of hydrocodone 5mg/acetaminophen 300 mg and a placebo pill.
Receives: Drug: opioid-containing analgesic
Non-OpioidActive comparatorCombination of ibuprofen 400 mg/acetaminophen 500 mg
Receives: Drug: two over-the-counter analgesics

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: End of day of surgery (day 1) and when waking up the next morning (1 night after surgery)

  2. 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).

    Measured: End of day of the second day after surgery (day 2) and when waking up the next morning (2nd night after surgery)

  3. 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).

    Measured: End of day of the third day after surgery (day 3) and when waking up the next morning (3rd night after surgery)

  4. 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).

    Measured: 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)

  5. 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?"

    Measured: At time of post-operative visit (day 9 +/- 5 days)

  6. 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).

    Measured: End of day of surgery (day 1) and when waking up the next morning (1 night after surgery)

  7. 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.)

    Measured: End of day of after surgery (day 2) and when waking up the next morning (2nd night after surgery

  8. 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).

    Measured: End of 2nd day of after surgery (day 3) and when waking up the next morning (3rd night after surgery)

  9. 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).

    Measured: 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)

  10. 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)

    Measured: End of day of surgery (day 1) and when waking up the next morning (1 night after surgery)

  11. 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.)

    Measured: End of day of after surgery (day 2) and when waking up the next morning (2nd night after surgery)

  12. 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).

    Measured: 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)

  13. 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).

    Measured: End of 2nd day of after surgery (day 3) and when waking up the next morning (3rd night after surgery)

Secondary outcomes (10)
  1. Number of Participants Receiving Rescue Medication

    Participant receiving additional pain medication (oxycodone) as study analgesic is not managing pain sufficiently

    Measured: At post operative visit (9 days after surgery +/- 5 days)

  2. 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.

    Measured: End of the day of surgery (day 1)

  3. 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.

    Measured: End of the first full day after surgery (day 2)

  4. 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.

    Measured: End of the second full day after surgery (day 3)

  5. 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.

    Measured: First 7 days after surgery

  6. 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.

    Measured: When first waking up the day after surgery

  7. 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.

    Measured: When first waking up the 2nd day after surgery

  8. 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.

    Measured: When first waking up the 3rd day after surgery

  9. 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.

    Measured: First 7 nights after surgery

  10. Potential for Opioid Tablet Diversion

    Number of returned opioid analgesic capsules at post operative visit (9 days after surgery +/- 5 days)

    Measured: At post operative visit (9 days after surgery +/- 5 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jun 2020
  2. Study start4 Jan 2021
  3. Primary completion7 Jul 2023
  4. Study completion24 Dec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,815 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04452344
Sponsor's protocol ID
Pro2020002299
Other IDs
5UH3DE028860-05
Acronym
OARS
Status last verified
Aug 2026
First submitted
7 Apr 2020
Last updated
31 Aug 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 39755971
  • 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.

    PubMed 35177108

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing opioid-containing analgesic and two over-the-counter analgesics in people with Opioid Use, run by Rutgers, The State University of New Jersey at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite Pain 1 (time frame: End of day of surgery (day 1) and when waking up the next morning (1 night after surgery)). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04452344, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.

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