Non-Opioid Pain Relievers for Opioid Use Disorder

(OARS Trial)

Recruiting at 4 trial locations

Overseen By Gary Warburton

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Rutgers, The State University of New Jersey

Must not be taking: CYP3A4 inhibitors, CNS depressants

Disqualifiers: Gastrointestinal bleeding, Renal disease, Hepatic disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 7 days

1815 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

If you are currently taking certain medications like CYP3A4 inhibitors or CNS depressants, you will need to stop taking them to participate in this trial.

What safety data exists for non-opioid pain relievers used in opioid use disorder?

Non-opioid pain relievers, like paracetamol and non-steroidal anti-inflammatory drugs, have been widely used and studied, but they still have potential safety concerns, such as adverse drug reactions and drug interactions. It's important for health professionals to monitor patients carefully to minimize risks. ^{1 2 3 4 5}

How is the drug 'Non-Opioid Pain Relievers for Opioid Use Disorder' different from other treatments?

This treatment is unique because it focuses on using non-opioid pain relievers, which are less likely to cause addiction, to manage pain in individuals with opioid use disorder. Unlike traditional opioid treatments that can lead to dependence, non-opioid options aim to provide pain relief without the risk of misuse. ^{4 6 7 8 9}

Research Team

Cecile A Feldman, DMD

Principal Investigator

Rutgers, The State University of New Jersey

Eligibility Criteria

Adults over 18, in good health, needing wisdom tooth removal can join this trial. They must understand English and consent to the study's procedures. Women should use contraception like pills or IUDs. Those with asthma, allergies to pain meds, heavy alcohol use, drug abuse history or taking certain medications cannot participate.

Inclusion Criteria

I am planning to have my wisdom teeth removed.

You are using an intrauterine device (IUD) for birth control.

I am currently using contraceptive pills.

Exclusion Criteria

I have a history of bleeding disorders.

I have a history of kidney disease, not including kidney stones.

I have a history of liver disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either a combination of hydrocodone/acetaminophen or ibuprofen/acetaminophen for post-operative pain management following 3rd molar extraction

7 days

Daily self-assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pain and satisfaction assessments

9 days

1 post-operative visit

Treatment Details

Interventions

• Opioid-containing Analgesic
• Over-the-counter Analgesics

Trial Overview The study is testing if a mix of two non-opioid painkillers works as well as an opioid-based one for managing post-wisdom tooth extraction pain. Participants will be randomly assigned to receive either the non-opioid combination or the standard opioid analgesic without knowing which one they're getting.

Participant Groups

Group I: Opioid Active Control 1 Intervention

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

Group II: Non-Opioid Active Control 1 Intervention

Combination of ibuprofen 400 mg/acetaminophen 500 mg

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

University of Illinois at Chicago

Collaborator

Trials

653

Recruited

1,574,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

National Institute of Dental and Craniofacial Research (NIDCR)

Collaborator

Trials

312

Recruited

853,000+

University of Rochester

Collaborator

Trials

883

Recruited

555,000+

University of Maryland, Baltimore

Collaborator

Trials

729

Recruited

540,000+

Findings from Research

This systematic review analyzed 16 randomized trials and 8 observational studies involving 1427 and 1190 patients, respectively, to evaluate the efficacy and safety of long-acting opioids for chronic non-cancer pain.

The review found insufficient evidence to conclude that different long-acting opioids have distinct efficacy or safety profiles compared to each other or to short-acting opioids, although some evidence suggested that long-acting and short-acting oxycodone are equally effective for pain control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of long-acting oral opioids for chronic non-cancer pain: a systematic review. Chou, R., Clark, E., Helfand, M.[2022]

Opioid medications, particularly those targeting the μ-opioid receptor (μOR), are the most effective for pain management but come with serious side effects like respiratory depression and dependence.

There is a critical need for the development of new μOR analgesics that maintain pain relief properties while minimizing or eliminating adverse effects, as highlighted by recent research advancements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Designing Safer Analgesics via μ-Opioid Receptor Pathways. Chan, HCS., McCarthy, D., Li, J., et al.[2018]

The review emphasizes that while analgesics, both non-opioid (like paracetamol and NSAIDs) and opioid medications, are commonly used for pain management, they carry significant risks of adverse drug reactions (ADRs) that can often be prevented.

Recognizing and understanding the safety issues associated with analgesics is crucial for healthcare professionals to ensure effective pain treatment while minimizing risks, highlighting the importance of careful patient monitoring and consideration of individual medical factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety issues of current analgesics: an update. Cazacu, I., Mogosan, C., Loghin, F.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of long-acting oral opioids for chronic non-cancer pain: a systematic review. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

"Safe and effective when used as directed": the case of chronic use of opioid analgesics. [2021]

3. Canada pubmed.ncbi.nlm.nih.gov

Retrospective analysis of opioid medication incidents requiring administration of naloxone. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Designing Safer Analgesics via μ-Opioid Receptor Pathways. [2018]

5. Romania pubmed.ncbi.nlm.nih.gov

Safety issues of current analgesics: an update. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Long-term opioid therapy for chronic pain: optimizing management, minimizing risk. [2013]

7. Slovakia pubmed.ncbi.nlm.nih.gov

5 most consumpted opioid analgesics in Slovakia in the year 2006--comparison to five other countries (Finland, Norway, Denmark, Spain, Australia). [2016]

8. China pubmed.ncbi.nlm.nih.gov

[Chinese guidelines for the treatment of chronic pain disorders with non-opioid analgesics]. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

The prevalence of opioid medication use among adults in the United States. [2022]