Methadone vs Buprenorphine for Opioid Use Disorder

Recruiting at 5 trial locations

Overseen By Ingrid Binswanger, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Yale University

Must be taking: MOUD

Disqualifiers: Pregnancy, Suicidal, Severe cognitive impairment, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two treatments, methadone and buprenorphine (a medication for opioid use disorder), to determine which is more effective when prescribed in a doctor's office and picked up at a pharmacy for individuals with opioid use disorder. It also examines the optimal setup for methadone treatment in a regular medical setting. Individuals starting a new treatment for opioid use disorder who have not taken similar medication for more than three days in the past week may be suitable candidates for this study. As a Phase 4 trial, this research aims to understand how these FDA-approved treatments can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have been on certain opioid treatments for more than 72 hours in the past week, you may not be eligible to participate.

What is the safety track record for methadone and buprenorphine?

Research has shown that both methadone and buprenorphine are safe and effective for treating opioid use disorder.

Studies indicate that methadone is a common treatment, with about 74% of patients completing a 24-week program, suggesting it is generally well-tolerated.

Buprenorphine has also undergone thorough research. Studies found that doses over 16 mg are safe and well-tolerated. Participants who took buprenorphine for more than six months continued to benefit without major side effects.

Both treatments have been used for a long time and are considered safe options for many people dealing with opioid use disorder. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they could change how we approach opioid use disorder management. Unlike traditional methadone treatment, which usually requires daily visits to specialized clinics, office-based methadone allows patients to receive their medication at a regular pharmacy, offering more convenience and accessibility. Similarly, office-based buprenorphine can be administered in extended-release formulations, potentially reducing the frequency of doses and improving adherence. Both treatments are integrated with additional behavioral therapies, which might enhance overall recovery by addressing the psychological aspects of addiction alongside the physical.

What evidence suggests that this trial's treatments could be effective for opioid use disorder?

This trial will compare methadone and buprenorphine for treating opioid use disorder. Studies have shown that both methadone and buprenorphine effectively treat this condition. Research indicates that methadone reduces cravings and keeps patients in treatment longer, with patients on methadone being 1.8 times more likely to remain in treatment compared to those on buprenorphine. Methadone is also known for reducing the risk of overdose and other opioid-related health issues. Buprenorphine, especially at higher doses, effectively reduces opioid use and related deaths. Both medications have proven to lower the risk of overdose and other negative health outcomes, making them valuable options for treating opioid use disorder. Participants in this trial will receive either methadone or buprenorphine, along with additional behavioral treatments. ^{1 3 6 7 8}

Who Is on the Research Team?

David Fiellin, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults over 18 who meet the criteria for Opioid Use Disorder (OUD) according to the DSM-5 and are starting a new medication treatment. Specific details on who can't join were not provided.

Inclusion Criteria

I have been diagnosed with opioid use disorder.

I am starting a new medication treatment for opioid use disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either office-based methadone or buprenorphine for opioid use disorder treatment, with additional behavioral treatments offered

24 weeks

Regular visits for medication administration and behavioral treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Buprenorphine
• Methadone

Trial Overview

The study compares two treatments for opioid addiction: methadone given at doctors' offices versus buprenorphine (BUP). It also looks into how well office-based methadone programs work.

How Is the Trial Designed?

Group I: Office-based methadone Experimental Treatment 1 Intervention

Under special Drug Enforcement Administration (DEA) exception, Clinician prescribes methadone and oral methadone is administered and/or dispensed at a pharmacy which also has an exception to do so. All randomized controlled trial (RCT) participants are offered additional behavioral treatments (e.g., individual, group, telehealth, phone-based).

Group II: Office-based buprenorphine (BUP) Active Control 1 Intervention

Clinician prescribes BUP formulations that are dispensed at a pharmacy or administered in the office (e.g., extended-release formulations). All RCT participants are offered additional behavioral treatments (e.g., individual, group, telehealth, phone-based).

Buprenorphine is already approved in United States, European Union for the following indications:

Approved in United States as Buprenorphine for:

• Moderate to severe opioid addiction (dependence)

Approved in European Union as Buprenorphine for:

• Opioid dependence

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Kaiser Permanente

Collaborator

Trials

563

Recruited

27,400,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

The Emmes Company, LLC

Industry Sponsor

Trials

149

Recruited

1,052,000+

Peter Ronco

The Emmes Company, LLC

Chief Executive Officer since 2023

BSc from Nottingham University

Dr. Joe Sliman

The Emmes Company, LLC

Chief Medical Officer since 2020

MD from Uniformed Services University of the Health Sciences, MPH from Johns Hopkins University, BSc in Molecular and Cell Biology from Pennsylvania State University

Boston Medical Center (BMC)

Collaborator

Trials

1

Recruited

600+

Hennepin Healthcare Research Institute

Collaborator

Trials

94

Recruited

77,100+

Alameda Health System

Collaborator

Trials

9

Recruited

4,100+

Marshall Health

Collaborator

Trials

1

Recruited

600+

Published Research Related to This Trial

Recent studies indicate that buprenorphine, when administered at adequate doses and with rapid induction, is as effective as methadone for maintaining treatment in opioid dependence, challenging previous perceptions of its efficacy.

Buprenorphine-based regimens not only enhance access to treatment but also offer a safer alternative for certain patients compared to methadone, making it a valuable option in opioid dependence therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine-based regimens and methadone for the medical management of opioid dependence: selecting the appropriate drug for treatment. Maremmani, I., Gerra, G.[2016]

In a study of 118 adults with moderate to severe opioid use disorder, higher doses of medication for opioid use disorder (MOUD) significantly improved retention rates, with an odds ratio of 4.71 for those on high doses.

Participants experiencing higher levels of pain interference were also more likely to remain on MOUD, suggesting that effective pain management may enhance treatment retention and provide dual benefits for both opioid use disorder and pain relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors associated with retention on medications for opioid use disorder among a cohort of adults seeking treatment in the community. Biondi, BE., Vander Wyk, B., Schlossberg, EF., et al.[2022]

Buprenorphine is as effective as methadone for opiate detoxification and maintenance but is safer in overdose situations, making it a preferable option for treatment.

Suboxone, a combination of buprenorphine and naloxone, is recommended for maintenance treatment due to its lower abuse potential, while Subutex (buprenorphine alone) is advised for pregnant women, highlighting the tailored approach to treatment based on patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine in the treatment of opiate dependence. Wesson, DR., Smith, DE.[2013]

A case report involving one patient showed that a rapid microinduction protocol for transitioning from methadone to buprenorphine was successful without causing precipitated withdrawal, indicating a safer method for patients with opioid use disorder.

This outpatient approach not only proved feasible but also cost-effective, suggesting it could help reduce barriers to adherence in opioid agonist therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid Transition From Methadone to Buprenorphine Utilizing a Micro-dosing Protocol in the Outpatient Veteran Affairs Setting. De Aquino, JP., Fairgrieve, C., Klaire, S., et al.[2022]

In a study involving 272 participants with opioid use disorder primarily using opioids other than heroin, higher doses of methadone were associated with better retention in treatment, suggesting that its full µ-opioid receptor agonism may enhance treatment adherence.

In contrast, the doses of buprenorphine/naloxone did not show a significant association with treatment retention or adverse events, indicating that while both treatments are used, methadone may be more effective for keeping patients in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations of methadone and buprenorphine-naloxone doses with unregulated opioid use, treatment retention, and adverse events in prescription-type opioid use disorders: Exploratory analyses of the OPTIMA study. Bakouni, H., McAnulty, C., Tatar, O., et al.[2023]

Citations

1.

nih.gov

nih.gov/news-events/news-releases/higher-doses-buprenorphine-may-improve-treatment-outcomes-people-opioid-use-disorder

Higher doses of buprenorphine may improve treatment ...

These findings suggest that higher buprenorphine doses could be more effective in managing opioid use disorder, which may be particularly relevant for ...

2.

nida.nih.gov

nida.nih.gov/news-events/news-releases/2024/09/higher-doses-of-buprenorphine-may-improve-treatment-outcomes-for-people-with-opioid-use-disorder

Higher doses of buprenorphine may improve treatment ...

Studies have shown that more than 16 mg of buprenorphine is safe and well tolerated in people with opioid use disorder in emergency department ...

3.

cdc.gov

cdc.gov/mmwr/volumes/73/wr/mm7325a1.htm

Treatment for Opioid Use Disorder: Population Estimates

Medications for opioid use disorder (OUD), particularly buprenorphine and methadone, substantially reduce overdose-related and overall mortality ...

4.

jamanetwork.com

jamanetwork.com/journals/jama/fullarticle/2825088

Buprenorphine/Naloxone vs Methadone for the Treatment ...

The risk of treatment discontinuation was higher among recipients of buprenorphine/naloxone compared with methadone (88.8% vs 81.5% within 24 months).

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S2949875923002060

Integrated analysis of phase 3 studies

Extending BUP-XR treatment beyond 6 months sustained improvement in opioid abstinence and was well tolerated, supporting clinical benefit up to 18 months.

6.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/10.1111/add.16600

Dose‐specific clinical outcomes in patients with opioid use ...

These data indicate that higher dosing of buprenorphine can confer a physiological benefit which, in turn, may improve outcomes and reduce harm ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6585403/

Buprenorphine Treatment for Opioid Use Disorder

The rate of relapse by the end of 24 weeks was 57% on buprenorphine versus 65% on injection naltrexone. Most of this difference could be accounted for by the ...

8.

indivior.com

indivior.com/en/media/press-releases/indivior-presents-new-data-at-cpdd-demonstrating-that-high-buprenorphine-exposure-may-improve-treatment-outcomes-in-high-fentanyl-users

Indivior Presents New Data at CPDD Demonstrating that ...

Both dosing regimens led to significant reductions in opioid use: the average weekly use dropped sharply from over 40 instances at screening to ...