Non-Opioid Pain Relievers for Opioid Use Disorder

(OARS Trial)

Not currently recruiting at 3 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a mix of over-the-counter pain relievers works as well as a common opioid painkiller after wisdom tooth removal. It aims to provide healthcare providers with better information on managing pain without relying on opioids. Participants will receive either a combination of ibuprofen and acetaminophen (over-the-counter analgesics) or an opioid-based painkiller (opioid-containing analgesic). This trial suits individuals planning to have their lower wisdom teeth removed and who are in good health overall. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to significant advancements in pain management.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that taking ibuprofen and acetaminophen together, both non-opioid pain relievers, is generally safe for most people. Studies indicate that this combination is well-tolerated, with serious side effects being uncommon when these medications are used together.

In a study with over 700 participants, this non-opioid combination proved safe for short-term use. The study also found it provided pain relief similar to opioid pain relievers, such as those containing hydrocodone.

Overall, evidence suggests that non-opioid pain relievers can be a safe choice for managing pain, especially for those who want to avoid opioids. Always consult a healthcare provider to determine if this option is suitable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for opioid use disorder because they offer a potentially safer alternative to traditional opioid painkillers, which often include medications like oxycodone or morphine. The non-opioid option in this study combines ibuprofen and acetaminophen, which may reduce pain effectively without the risk of addiction associated with opioids. This alternative could decrease opioid dependency while still managing pain, addressing a critical need for safer pain management strategies.

What evidence suggests that this trial's treatments could be effective for post-surgical pain management?

This trial will compare the effectiveness of a non-opioid combination of ibuprofen and acetaminophen with an opioid-containing analgesic. Studies have shown that taking ibuprofen and acetaminophen together can relieve pain as well as, or even better than, opioid medications. This non-opioid combination effectively reduces pain after surgeries like wisdom tooth removal. Research indicates that using these over-the-counter drugs together provides significant pain relief without the side effects or risks associated with opioids. In fact, no major difference in pain relief exists when comparing ibuprofen and acetaminophen to a mix of an opioid and acetaminophen. Overall, this makes the combination of ibuprofen and acetaminophen a strong option for safely managing acute pain. ^{6 7 8 9 10}

Who Is on the Research Team?

Cecile A Feldman, DMD

Principal Investigator

Rutgers, The State University of New Jersey

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1.

tandfonline.com

tandfonline.com/doi/full/10.1080/00325481.2024.2382671

Ibuprofen/acetaminophen fixed-dose combination as an ...

Across studies, IBU/APAP FDCs consistently demonstrated pain relief similar to or better than opioid and nonopioid comparators and reliably ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5818795/

Effect of a Single Dose of Oral Opioid and Nonopioid ...

There were no clinically important differences in pain reduction at 2 hours with ibuprofen and acetaminophen or 3 different opioid and acetaminophen ...

3.

journals.lww.com

journals.lww.com/ebp/fulltext/2020/02000/nonopioid_analgesics_as_effective_as_opioids_for.6.aspx

Nonopioid analgesics as effective as opioids for acute pain?

There is no significant difference in pain reduction between treatment with single-dose ibuprofen and acetaminophen versus opioid and acetaminophen combination ...

4.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0196064420312658

A Randomized Trial Comparing the Efficacy of Five Oral ...

There are few ED studies. One found the combination of 1,000 mg of acetaminophen and 800 mg of ibuprofen to be no more effective than the individual components.

5.

bpspubs.onlinelibrary.wiley.com

bpspubs.onlinelibrary.wiley.com/doi/10.1002/bcp.70180

Combination vs. single‐drug nonprescription analgesics for ...

The data suggest that combination nonprescription products are more effective than monotherapy for managing postoperative pain and, to some ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6371943/

An integrated safety analysis of combined acetaminophen and ...

Overall, the FDC is well tolerated and has a strong safety profile at single and multiple doses with improved efficacy over monotherapy.

7.

trialsjournal.biomedcentral.com

trialsjournal.biomedcentral.com/articles/10.1186/s13063-022-06064-8

The Opioid Analgesic Reduction Study (OARS)—a ...

We hypothesize that a combination of acetaminophen and ibuprofen (NON-OPIOID) is non-inferior to the most commonly prescribed opioid analgesic, ...

8.

jamanetwork.com

jamanetwork.com/journals/jama/fullarticle/2661581

Effect of a Single Dose of Oral Opioid and Nonopioid ...

There were no clinically important differences in pain reduction at 2 hours with ibuprofen and acetaminophen or 3 different opioid and acetaminophen ...

9.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8851821/

The Opioid Analgesic Reduction Study (OARS)—a ...

We hypothesize that a combination of acetaminophen and ibuprofen (NON-OPIOID) is non-inferior to the most commonly prescribed opioid analgesic, hydrocodone ...

10.

tandfonline.com

tandfonline.com/doi/full/10.1080/00325481.2021.1912466

Safety and tolerability of fixed-dose combinations ...

This pooled analysis of data from more than 700 subjects indicates that a single dose or short course of an FDC of IBU 250 mg/APAP 500 mg as OTC use is safe and ...