Opioid Analgesic Reduction Study (OARS)

• ClinicalTrials.gov Identifier: NCT04452344
• Recruitment Status: Recruiting
• First Posted: June 30, 2020
• Last Update Posted: January 14, 2022
• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: National Institute of Dental and Craniofacial Research (NIDCR); University of Rochester; University of Maryland, Baltimore; University of Illinois at Chicago; University of Michigan
• Information provided by (Responsible Party): Cecile A. Feldman, DMD, Rutgers, The State University of New Jersey

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Opioid Use	Drug: opioid-containing analgesic; Drug: two over-the-counter analgesics	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1800 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Opioid Analgesic Reduction Study (OARS): Managing Acute Post-Operative Surgical Pain
• Actual Study Start Date: January 4, 2021
• Estimated Primary Completion Date: December 31, 2024
• Estimated Study Completion Date: December 31, 2025

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. Brief Pain Inventory pain scale using Numeric Rating Scale [ Time Frame: the first 24 hours post surgery ]
   Mean score (scale of 0 to 10, 0=no pain, 10=worst imaginable pain)
2. Brief Pain Inventory pain scale using Numeric Rating Scale [ Time Frame: the first 48 hours post surgery ]
   Mean score (scale of 0 to 10, 0=no pain, 10=worst imaginable pain)
3. Brief Pain Inventory pain scale using Numeric Rating Scale [ Time Frame: the first 7 days post surgery ]
   Mean score (scale of 0 to 10, 0=no pain, 10=worst imaginable pain)
4. PTSS satisfaction questions assessing overall satisfaction [ Time Frame: At post operative visit (9 days after surgery +/- 5 days) ]

   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)

Secondary Outcome Measures :

1. Adverse events experienced [ Time Frame: Total events recorded each morning and evening after surgery for the first 24 hours post surgery ]
   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)
2. Adverse events experienced [ Time Frame: Total events recorded each morning and evening after surgery for the first 48 hours post surgery ]
   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)
3. Adverse events experienced [ Time Frame: Total events recorded each morning and evening for the first 7 days post surgery ]
   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)
4. Pain interference (daily function) [ Time Frame: Day 2 post surgery (recorded the evening of day 2) ]
   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}
5. Pain interference (daily function) [ Time Frame: Days 2 and 3 post surgery (recorded the evenings of days 2 and 3) ]
   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}
6. Pain interference (daily function) [ Time Frame: First 7 days post surgery ]
   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}
7. Sleep quality (Questions from PSQ-3) [ Time Frame: For the first night post surgery ]
   • 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)
8. Sleep quality (Questions from PSQ-3) [ Time Frame: For the first 2 nights post surgery ]
   • 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)
9. Sleep Quality (Questions from PSQ-3) [ Time Frame: For the first 7 nights post surgery ]
   • 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)
10. Sleep Quality (PSQ-3) [ Time Frame: Recorded during Visit 2 (Post operative visit 9 days +/-5 days post surgery) ]
    • 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
11. Overall satisfaction with sleep [ Time Frame: For the first 7 evenings post surgery ]
    NRS where 0=never, 10=always
12. Overall satisfaction with sleep [ Time Frame: For the first 7 evenings post surgery ]
    From PTSS: Rating the overall quality of last night's sleep {NRS where 0=excellent and10=very poor}
13. Potential for opioid tablet diversion [ Time Frame: At post operative visit (9 days after surgery +/- 5 days) ]
    Number of returned analgesic capsules at post operative visit (9 days after surgery +/- 5 days)

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Julie Chapman-Greene, PhD; 973-972-3620; chapmaje@sdm.rutgers.edu

Contact: Janine Fredericks-Younger, DMD; 973-972-1679; frederja@sdm.rutgers.edu

Locations

United States, Illinois

University of Illinois at Chicago; Recruiting

Chicago, Illinois, United States, 60612

Contact: Michael Miloro, DMD, MD 312-996-1052 mmiloro@uic.edu

Sub-Investigator: Michael Miloro, DMD, MD

United States, Maryland

University of Maryland; Recruiting

Baltimore, Maryland, United States, 21201

Contact: Gary Warburton, DDS 410-706-7060 GWarburton@umaryland.edu

Sub-Investigator: Gary Warburton, DDS

United States, Michigan

University of Michigan; Recruiting

Ann Arbor, Michigan, United States, 48109

Contact: Brent Ward, DMD, MD 734-936-5941 bward@med.umich.edu

Sub-Investigator: Brent Ward, DMD, MD

United States, New Jersey

Rutgers School of Dental Medicine; Recruiting

Newark, New Jersey, United States, 07101

Contact: Vincent Zaccardi, DMD, MD 973-972-7462 ziccarvb@sdm.rutgers.edu

Sub-Investigator: Vincent Zaccardi, DMD, MD

Principal Investigator: Cecile Feldman, DMD

United States, New York

University of Rochester; Recruiting

Rochester, New York, United States, 14620

Contact: Hans Malmstrom, DDS 585-273-5087 Hans_Malmstrom@URMC.Rochester.edu

Sub-Investigator: Hans Malmstrom, DDS

Sponsors and Collaborators

Rutgers, The State University of New Jersey

National Institute of Dental and Craniofacial Research (NIDCR)

University of Rochester

University of Maryland, Baltimore

University of Illinois at Chicago

University of Michigan

Investigators

• Principal Investigator: Cecile A Feldman, DMD; Rutgers, The State University of New Jersey

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Cecile A. Feldman, DMD, Dean and Professor, Rutgers, The State University of New Jersey
• ClinicalTrials.gov Identifier: NCT04452344
• Other Study ID Numbers: Pro2020002299; 1UG3DE028860-01 ( U.S. NIH Grant/Contract )
• First Posted: June 30, 2020
• Last Update Posted: January 14, 2022
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Time Frame: 12 months after publication
• Access Criteria: Request data access from the PI.

• 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

Keywords provided by Cecile A. Feldman, DMD, Rutgers, The State University of New Jersey:

3rd molar extraction pain model; Opioid Analgesics; Opioid Diversion; Over the counter analgesics; Acetaminophen; Ibuprofen; Hydrocodone; Opioid Addiction; Pain Management; Satisfaction

Additional relevant MeSH terms:

Analgesics; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents