Buprenorphine + Antibiotics for Opioid Use Disorder and Infections

(BOPAT Trial)

Overseen By Connor M VanMeter

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Laura Fanucchi

Must be taking: Buprenorphine, Antibiotics

Disqualifiers: Stroke, Heart failure, Pregnancy, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks a safe and effective treatment for opioid use disorder alongside severe infections from injection drug use. Researchers are testing whether combining buprenorphine, a medication for opioid addiction, with antibiotics administered outside the hospital (known as Outpatient Parenteral Antibiotic Therapy or OPAT) can better manage these conditions. Participants will receive either this new approach or the usual care. The trial seeks individuals with opioid use disorder who require antibiotics for severe infections and are open to buprenorphine treatment.

As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Research has shown that using buprenorphine with antibiotics is generally safe for people with opioid addiction and serious infections. Studies indicate that this treatment is as well-tolerated as standard care. Patients reported no major side effects different from those seen with usual treatments. Additionally, buprenorphine is already known to be safe for treating opioid addiction, which enhances confidence in its safety when combined with antibiotics. Overall, this treatment appears to be a safe option for managing both addiction and infections. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of buprenorphine and outpatient parenteral antibiotic therapy (OPAT) for opioid use disorder (OUD) and severe injection-related infections (SIRI) because it offers a unique dual approach. Unlike standard treatments that typically focus on either managing OUD or treating infections separately, this approach integrates both, potentially improving outcomes for patients who struggle with both conditions simultaneously. Buprenorphine helps manage opioid dependency, while OPAT allows for the treatment of infections outside the hospital, promoting quicker recovery and reducing healthcare costs. This dual-action strategy could revolutionize care by addressing both the addiction and its complications in a coordinated manner.

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

Research has shown that buprenorphine effectively treats opioid use disorder (OUD). Studies have found it reduces overdoses and serious health problems related to opioids. Doses exceeding 16 mg of buprenorphine are safe and well-tolerated for people with OUD. In this trial, one group of participants will receive buprenorphine along with outpatient parenteral antibiotic therapy (OPAT), which involves receiving antibiotics through a needle at home. Research indicates that OPAT is safe and effective for people who inject drugs, with results similar to hospital care. Overall, combining buprenorphine with OPAT could safely and effectively treat both OUD and related infections. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for individuals with opioid use disorder who also have severe injection-related infections requiring IV antibiotics. Participants must be willing to take buprenorphine, anticipate being discharged home, and live within a 60-minute drive of Lexington, KY. Pregnant individuals or those with certain medical conditions like end-stage organ disease or heart failure are excluded.

Inclusion Criteria

I am taking antibiotics for a severe infection from an injection.

I need IV antibiotics.

I am willing to take buprenorphine for treatment.

Exclusion Criteria

You are allergic to buprenorphine.

I have severe liver or kidney disease.

current pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive outpatient parenteral antibiotic therapy (OPAT) and buprenorphine for opioid use disorder

12 weeks

Regular outpatient visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Buprenorphine
• Outpatient Parenteral Antibiotic Therapy

Trial Overview The study is testing an integrated outpatient treatment combining Buprenorphine for opioid addiction and either standard care or Outpatient Parenteral Antibiotic Therapy for severe infections. The goal is to see if this approach safely manages patients' conditions outside the hospital.

How Is the Trial Designed?

Group I: Outpatient Parenteral Antibiotic Therapy (OPAT) Experimental Treatment 1 Intervention

Patients with opioid use disorder (OUD) and severe, injection-related infections (SIRI) will be treated with buprenorphine and be discharged with outpatient parenteral antibiotic therapy (OPAT).

Group II: Treatment as Usual (TAU) Active Control 1 Intervention

Patients with OUD and severe, injection-related infections (SIRI) will receive usual care.

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?

Laura Fanucchi

Lead Sponsor

Trials

2

Recruited

110+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

In a study of 72 patients undergoing pacemaker implantation or substitution, short-term treatment with an imipenem-cilastatin combination was found to be effective in reducing the risk of infection.

After 30 months of follow-up, the treatment demonstrated significant advantages, suggesting it may be beneficial for patients with conditions that increase infection risk during such procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Short-term perioperative antibacterial prophylaxis using imipenem-cilastatin versus acylureide penicillins in pacemaker implantation. A 30-month follow-up]. Veneziani, N., De Pasquale, C., Baglietto, M.[2018]

Buprenorphine is a safe and effective treatment for opioid dependence, particularly when combined with naloxone, which reduces its potential for abuse.

New regulations enable certified physicians to prescribe buprenorphine in their offices, significantly improving patient access to this important treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine maintenance: a new treatment for opioid dependence. Collins, GB., McAllister, MS.[2019]

In a study of 31 hospitalized patients with bacterial infections, those treated with imipenem/cilastatin had a higher cure rate (13 out of 16) compared to those treated with cefotaxime (9 out of 15), indicating greater efficacy of imipenem/cilastatin for these infections.

Both treatments had similar safety profiles, with phlebitis occurring in 9 patients on imipenem/cilastatin and 8 on cefotaxime, and only one case of diarrhea in the cefotaxime group, suggesting that imipenem/cilastatin may be a more effective option without significantly increasing safety risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective randomized comparison of imipenem/cilastatin and cefotaxime for treatment of lung, soft tissue, and renal infections. Diaz-Mitoma, F., Harding, GK., Louie, TJ., et al.[2019]

In a study involving rat models of intra-abdominal abscesses, cefoperazone, cefotaxime, and cefpirome were found to be significantly less effective against an extended-spectrum beta-lactamase-producing strain of Klebsiella pneumoniae compared to imipenem.

The combination of cefoperazone and sulbactam showed better efficacy than the standard cephalosporins, highlighting the importance of treatment choice in infections caused by resistant bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of different beta-lactams against an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain in the rat intra-abdominal abscess model. Rice, LB., Yao, JD., Klimm, K., et al.[2021]

Garenoxacin (GARX) demonstrated significant synergistic antibacterial activity when combined with various non-quinolone antibiotics against non-fermentative Gram-negative bacteria, suggesting it could enhance treatment effectiveness for infections caused by these pathogens.

The study found that combinations of GARX with drugs like cefepime and imipenem showed the most frequent synergy, indicating potential for improved outcomes in treating infections from bacteria like Pseudomonas aeruginosa and Stenotrophomonas maltophilia, even in strains that are resistant or less susceptible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic activity of the novel des-fluoro(6) quinolone, garenoxacin (BMS-284756), in combination with other antimicrobial agents against Pseudomonas aeruginosa and related species. Fung-Tomc, JC., Gradelski, E., Valera, L., et al.[2019]

In an animal study with 66 male Wistar rats, combination therapies of moxifloxacin or flucloxacillin with rifampin significantly reduced bacterial counts in bone, soft tissue, and biofilm associated with Staphylococcus aureus infections, while monotherapies were ineffective.

The study highlighted that monotherapy with moxifloxacin or flucloxacillin did not significantly decrease microbial counts, and rifampin alone only reduced biofilm counts, indicating that combination therapy is crucial to effectively treat implant-associated infections and prevent antibiotic resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of antibiotic treatment of implant-associated Staphylococcus aureus infections with moxifloxacin, flucloxacillin, rifampin, and combination therapy: an animal study. Greimel, F., Scheuerer, C., Gessner, A., et al.[2018]

In a study of 94 diabetic patients with lower extremity infections, imipenem/cilastatin demonstrated a high efficacy, with 92% of patients either cured or improved and 79% of pathogens eradicated.

The safety profile of imipenem/cilastatin was consistent with previous reports, indicating it is a safe and effective treatment option for infections in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imipenem/cilastatin treatment of lower extremity skin and soft tissue infections in diabetics. Calandra, GB., Raupp, W., Brown, KR.[2018]

Antibiotics can cause serious side effects and drug-drug interactions, which are significant contributors to patient harm and increased healthcare costs, as highlighted by a recent hospital study identifying drug-related toxicity as a common cause of death.

The chapter emphasizes the importance of understanding antibiotic-induced adverse events, especially in vulnerable populations such as patients with renal insufficiency, those on immunosuppressive therapy, pregnant women, the elderly, and HIV-infected individuals, to prevent complications and improve patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic side effects. Gleckman, RA., Czachor, JS.[2005]

In a double-blind randomized trial involving diabetic patients with limb-threatening pedal infections, both imipenem/cilastatin (I/C) and ampicillin/sulbactam (A/S) showed similar efficacy, with cure rates of 85% for I/C and 81% for A/S after definitive treatment.

The safety profiles were comparable, with similar rates of adverse events in both groups, indicating that both antibiotics are effective and safe options for treating these infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of ampicillin/sulbactam versus imipenem/cilastatin in the treatment of limb-threatening foot infections in diabetic patients. Grayson, ML., Gibbons, GW., Habershaw, GM., et al.[2022]

In a study of 34 patients with osteomyelitis treated with imipenem/cilastatin for an average of 32.5 days, 74% of patients experienced either a cure or improvement, indicating its efficacy as a treatment for complicated polymicrobial infections.

While some adverse effects like nausea and diarrhea were noted, only three patients needed to stop treatment, suggesting that imipenem/cilastatin is generally safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imipenem/cilastatin in the treatment of osteomyelitis. MacGregor, RR., Gentry, LO.[2019]

Imipenem/cilastatin is an effective single-agent treatment for osteomyelitis, showing low failure rates (10-30%) comparable to other antibiotics like cefotaxime and ceftazidime, based on a study of 243 patients.

While side effects were generally minimal, some patients experienced reversible neutropenia and other complications, indicating that monitoring is necessary during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role for newer beta-lactam antibiotics in treatment of osteomyelitis. Gentry, LO.[2019]

Buprenorphine and its combination with naloxone (Suboxone) have been officially added to the list of approved medications for treating opioid dependence in federally certified treatment programs, alongside methadone and ORLAAM.

These medications will be subject to the same federal treatment standards as existing opioid treatments, ensuring consistent safety and efficacy protocols in managing opioid dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid drugs in maintenance and detoxification treatment of opiate addiction; addition of buprenorphine and buprenorphine combination to list of approved opioid treatment medications. Interim final rule. [2013]

Buprenorphine is widely abused in the Czech Republic, often becoming the main drug of choice for some individuals, particularly when used intravenously.

Introducing a combination of buprenorphine and naloxone (Suboxone) could help address this abuse issue, as Suboxone is less likely to be misused intravenously, but its registration has not yet been pursued by manufacturers in the country.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Abuse of buprenorphine becomes a problem of the Czech Republic]. Nespor, K., Csémy, L.[2013]

Buprenorphine is an opioid medication used for treating opioid dependence and managing moderate to severe pain, and it can be prescribed to pregnant women as part of their treatment for opioid addiction.

The chapter details a method for quantifying buprenorphine and its metabolite norbuprenorphine in meconium using liquid chromatography tandem mass spectrometry (LC-MS/MS), which is important for monitoring drug exposure in newborns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitation of Total Buprenorphine and Norbuprenorphine in Meconium by LC-MS/MS. Marin, SJ., McMillin, GA.[2016]

Citations

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2. 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 ...

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2760032

Comparative Effectiveness of Different Treatment Pathways ... Treatment with buprenorphine or methadone was associated with reductions in overdose and serious opioid-related acute care use compared with other treatments.

4. 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.

5. recoveryanswers.org recoveryanswers.org/research-post/injectable-buprenorphine-1-year-outcomes/

Injectable buprenorphine for opioid use disorder: Effects on ... Previous studies have demonstrated the ability of monthly buprenorphine injections to enhance recovery outcomes after six months of treatment. However, little ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9277431/

a randomized clinical trial of integrated outpatient treatment of ... This study evaluates the efficacy and cost-effectiveness of an integrated care model combining Buprenorphine treatment of OUD with OPAT for SIRI (B-OPAT)

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7931831/

Outpatient Parenteral Antimicrobial Therapy Plus ... An innovative care model combining outpatient parenteral antimicrobial therapy with buprenorphine treatment had similar clinical and drug use outcomes to usual ...

8. journals.sagepub.com journals.sagepub.com/doi/abs/10.1177/20499361221108005

a randomized clinical trial of integrated outpatient treatment ... Key secondary OUD outcomes include self-reported number of days of illicit opioid abstinence and 12-week retention in buprenorphine treatment.

9. academic.oup.com academic.oup.com/jid/article/222/Supplement_5/S494/5900587

Feasibility and Safety of Outpatient Parenteral Antimicrobial ... Outpatient parenteral antimicrobial therapy with addiction treatment may be feasible and safe for PWID with serious infections. bacterial ...

10. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0091743519302361

Integrated outpatient treatment of opioid use disorder and ... A novel, integrated care model was developed where patients with OUD and SIRI receive addiction consultation and buprenorphine induction while hospitalized.