NCT04452344

Brief 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 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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,815

participants targeted

Target at P75+ for phase_3

Timeline
2mo left

Started Jan 2021

Longer than P75 for phase_3

Geographic Reach
1 country

5 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress97%
Jan 2021Jul 2026

First Submitted

Initial submission to the registry

April 7, 2020

Completed
3 months until next milestone

First Posted

Study publicly available on registry

June 30, 2020

Completed
6 months until next milestone

Study Start

First participant enrolled

January 4, 2021

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 7, 2023

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

July 30, 2024

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2026

Expected
Last Updated

March 31, 2026

Status Verified

March 1, 2026

Enrollment Period

2.5 years

First QC Date

April 7, 2020

Results QC Date

May 15, 2024

Last Update Submit

March 17, 2026

Conditions

Opioid Use

Keywords

3rd molar extraction pain modelOpioid AnalgesicsOpioid DiversionOver the counter analgesicsAcetaminophenIbuprofenHydrocodoneOpioid AddictionPain ManagementSatisfaction

Outcome Measures

Primary Outcomes (13)

  • 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)

  • 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)

  • 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)

Secondary Outcomes (10)

  • Number of Participants Receiving Rescue Medication

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

  • Pain Interference 1

    End of the day of surgery (day 1)

  • Pain Interference 2

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

  • Pain Interference 3

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

  • Pain Interference All

    First 7 days after surgery

  • +5 more secondary outcomes

Study Arms (2)

Opioid

ACTIVE COMPARATOR

Combination analgesic of hydrocodone 5mg/acetaminophen 300 mg and a placebo pill.

Drug: opioid-containing analgesic

Non-Opioid

ACTIVE COMPARATOR

Combination of ibuprofen 400 mg/acetaminophen 500 mg

Drug: two over-the-counter analgesics

Interventions

opioid-containing analgesicDRUG

hydrocodone/ acetaminophen combination product

Opioid
two over-the-counter analgesicsDRUG

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

Non-Opioid

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Rutgers School of Dental Medicine

Newark, New Jersey, 07101, United States

Location

University of Rochester

Rochester, New York, 14620, United States

Location

Related Publications (2)

  • 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.

    PMID: 39755971DERIVED

  • 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.

    PMID: 35177108DERIVED

MeSH Terms

Conditions

Opioid-Related DisordersAgnosiaPersonal Satisfaction

Condition Hierarchy (Ancestors)

Narcotic-Related DisordersSubstance-Related DisordersChemically-Induced DisordersMental DisordersPerceptual DisordersNeurobehavioral ManifestationsNeurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and SymptomsBehavior

Results Point of Contact

Title
Cecile A. Feldman, DMD
Organization
Rutgers University School of Dental Medicine
feldman@rutgers.edu
973-972-4634

Study Officials

  • Cecile A Feldman, DMD

    Rutgers, The State University of New Jersey

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
This study was a double-blinded study. The participant, care provider, site directors and site research coordinators were all blinded.
Purpose
SUPPORTIVE CARE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Dean and Professor

Study Record Dates

First Submitted

April 7, 2020

First Posted

June 30, 2020

Study Start

January 4, 2021

Primary Completion

July 7, 2023

Study Completion (Estimated)

July 31, 2026

Last Updated

March 31, 2026

Results First Posted

July 30, 2024

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will share

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.

Time Frame
12 months after publication
Access Criteria
Request data access from the PI.

Locations

US(5)