Oritavancin + Medication for Infections and Opioid Use Disorder

(AIM-STOP Trial)

Overseen By Lisa Anderson

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Maryland, Baltimore

Must be taking: Medication for opioid use disorder

Must not be taking: Prohibited concomitant medications

Disqualifiers: Hypersensitivity, Liver disease, Kidney disease, 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 tests a new method for treating infections in individuals with opioid use disorder. Instead of staying in a nursing facility for IV antibiotics, patients may receive weekly doses of the antibiotic oritavancin while beginning treatment for their opioid use disorder. Researchers are studying this approach to determine if it is as effective as standard care. Suitable candidates include those hospitalized for a drug-related infection requiring long-term antibiotic treatment who are not currently on opioid treatment but are willing to begin it. As a Phase 4 trial, this study involves an FDA-approved treatment, aiming to understand its benefits for a broader patient population.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that you cannot be on prohibited concomitant medications. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What is the safety track record for oritavancin?

Research shows that oritavancin is generally safe and well-tolerated. In past studies, most participants did not experience serious side effects. However, some individuals have had serious allergic reactions, requiring the medication to be stopped. Oritavancin is already FDA-approved for certain infections, indicating its safety for these uses is well-understood. This trial explores a new application, so staying informed and discussing any concerns with a healthcare provider is advisable. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Oritavancin is unique because it offers a one-time, single-dose treatment for infections in people with opioid use disorder, which is a game-changer compared to traditional IV antibiotics that require multiple doses over several days or weeks. This single-dose convenience is particularly beneficial for individuals who might find it challenging to adhere to prolonged treatment regimens. Researchers are excited about oritavancin because it can simplify the treatment process, potentially improving adherence and outcomes for patients with these complex medical needs.

What evidence suggests that oritavancin might be an effective treatment for infections and opioid use disorder?

Research shows that oritavancin effectively combats bacterial infections, including those caused by Staphylococcus aureus, a common bacterium in infections related to drug use. Studies have found that oritavancin can treat serious bacterial skin infections, even those resistant to methicillin, a common antibiotic. Evidence from real-world use supports its effectiveness in outpatient settings, reducing hospital readmissions for similar infections. This medication is especially convenient because it requires only weekly administration, minimizing the need for daily IV treatments. Overall, oritavancin has proven effective for treating certain bacterial infections, making it a promising option for patients with opioid use disorder who need outpatient care. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with opioid use disorder who have infections from drug use, need long-term IV antibiotics, and are stable enough to leave the hospital. They must not be on opioid therapy but willing to start MOUD (like methadone/suboxone), follow up at a clinic, and if female, agree to effective birth control or be postmenopausal/sterilized.

Inclusion Criteria

I have an infection from drug use requiring long-term IV antibiotics.

Able and willing to sign consent

I have used opioids not prescribed to me in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intermittent outpatient oritavancin therapy dosed weekly combined with initiation and continuation of medication assisted treatment for opioid use disorder

12 weeks

Weekly visits for oritavancin administration and MOUD optimization

Follow-up

Participants are monitored for cure/completion of therapy and MOUD outcomes

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Oritavancin

Trial Overview The study tests weekly doses of an antibiotic called Oritavancin in outpatient settings combined with MOUD for treating serious infections related to drug use. It's a 12-week open-label study where patients also receive care coordination and support from peer recovery coaches.

How Is the Trial Designed?

Group I: Historical outcomes with standard of care treatment Experimental Treatment 1 Intervention

Historical outcomes with standard of care treatment involving IV antibiotics administered in a skilled nursing facility will be compared

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

Approved in United States as Orbactiv/Kimyrsa for:

• Acute bacterial skin and skin structure infections

Approved in European Union as Orbactiv/Kimyrsa for:

• Acute bacterial skin and skin structure infections

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Published Research Related to This Trial

The newly discovered compound, identified as 10, is a potent antagonist of the opioid receptor-like 1 (ORL1) with strong selectivity, meaning it effectively targets ORL1 without significantly affecting other opioid receptors.

Compound 10 has demonstrated in vivo efficacy after oral administration, and it is currently undergoing clinical trials, indicating its potential as a therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of an orally active opioid receptor-like 1 (ORL1) receptor antagonist 4-{3-[(2R)-2,3-dihydroxypropyl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl}-1-[(1S,3S,4R)-spiro[bicyclo[2.2.1]heptane-2,1'-cyclopropan]-3-ylmethyl]piperidine as clinical candidate. Satoh, A., Sagara, T., Sakoh, H., et al.[2022]

A new compound, 2-(tert-butylthio)-5-chloro-6-[(2R)-4-(2-hydroxyethyl)-2-methylpiperazin-1-yl]-1H-benzimidazole, was developed as a highly potent and selective antagonist for the ORL1 receptor, showing promise for oral administration and effective brain penetration.

The optimization process involved modifying the piperazine ring, which enhanced the compound's selectivity and potency, while also allowing for control over its activity on other opioid receptors through stereochemistry adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel ORL1-selective antagonists with oral bioavailability and brain penetrability. Okamoto, O., Kobayashi, K., Kawamoto, H., et al.[2022]

The study developed a predictive model for the efficacy of dual-acting kappa opioid receptor (KOR) agonist and mu opioid receptor (MOR) partial agonist ligands, showing that modifications to the chemical structure can influence receptor activity.

In vivo tests of two selected ligands confirmed their KOR activity and some MOR activity, indicating that in vitro efficacy measures can reliably predict how these compounds will perform in living organisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Orvinols with mixed kappa/mu opioid receptor agonist activity. Greedy, BM., Bradbury, F., Thomas, MP., et al.[2023]

Compound 39 (MK-1925) was identified as a selective and orally available antagonist for the opioid receptor-like 1 (ORL1), demonstrating the potential for effective brain penetration.

In vivo studies showed that MK-1925 is effective after oral dosing, making it a promising candidate for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of MK-1925: a selective, orally active and brain-penetrable opioid receptor-like 1 (ORL1) antagonist. Kobayashi, K., Tsujita, T., Ito, H., et al.[2022]

The compound 1d, a phenyl ring analogue of buprenorphine, shows high affinity for μ, κ, and δ opioid receptors while also having moderate affinity for nociceptin opioid peptide receptors, making it a promising candidate for preventing relapse in drug abuse.

In vivo studies confirmed that 1d does not exhibit opioid agonist activity, effectively acting as an antagonist to both morphine and ethylketocyclazocine, which supports its potential as a safe treatment option without the risk of opioid-like effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selectively promiscuous opioid ligands: discovery of high affinity/low efficacy opioid ligands with substantial nociceptin opioid peptide receptor affinity. Kumar, V., Ridzwan, IE., Grivas, K., et al.[2022]

The review of 18 studies indicates that treating ADHD in patients with opioid use disorder (OUD) can lead to better retention in OUD treatment programs and improvements in ADHD severity.

While the specific medications for OUD treatment could not be prioritized, the findings suggest that addressing ADHD symptoms is important for reducing illicit substance abuse in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gaps in Evidence-based Treatment of Concurrent Attention Deficit Hyperactivity Disorder and Opioid Use Disorder: A Scoping Review. Ramey, OL., Bonny, AE., Silva Almodóvar, A., et al.[2023]

An integrated drug repurposing strategy identified five candidate medications (tramadol, olanzapine, mirtazapine, bupropion, and atomoxetine) that significantly increase the odds of remission from opioid use disorder (OUD), based on analysis of electronic health records from over 72.9 million patients.

These candidate drugs target multiple genes and pathways associated with OUD, suggesting they may effectively address both OUD and related comorbid conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug repurposing for opioid use disorders: integration of computational prediction, clinical corroboration, and mechanism of action analyses. Zhou, M., Wang, Q., Zheng, C., et al.[2023]

Kimyrsa, a new formulation of oritavancin, offers a shorter infusion time and greater flexibility with solution compatibility while maintaining a similar pharmacokinetic and microbiologic profile to the original formulation.

Despite these advantages, Kimyrsa currently lacks significant real-world experience compared to other lipoglycopeptides, making its exact role in treatment uncertain but likely similar to that of the original formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kimyrsa and Orbactiv - A Tale of Two Formulations. Jackson, BT., Cluck, DB., Henao-Martínez, AF., et al.[2023]

In a study of 336 patients treated with elbasvir/grazoprevir (EBR/GZR), an impressive 318 (95%) achieved sustained virologic response at 12 weeks (SVR12), indicating high efficacy in real-world settings.

However, people who injected drugs (PWID) with recent drug use had significantly lower SVR rates (69%) compared to those without recent drug use (97%), highlighting the need for targeted interventions for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of recent drug use on the efficacy of elbasvir/grazoprevir for HCV-infected people on opioid agonist therapy. Macías, J., Téllez, F., de Los Santos, I., et al.[2022]

Oritavancin is a new lipoglycopeptide antibiotic that is as effective as vancomycin for treating acute bacterial skin infections, based on phase 3 trials involving adult patients, with results assessed 48-72 hours after treatment initiation.

It is well tolerated with mostly mild side effects, and its single-dose administration offers advantages like reduced hospital stays and no need for dosage adjustments in patients with liver or kidney issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oritavancin: a review in acute bacterial skin and skin structure infections. Syed, YY., Scott, LJ.[2018]

Citations

1. kimyrsa.com kimyrsa.com/real-world-data/

Real-World Data A retrospective real-world study of readmission rates of patients treated in the outpatient setting with oritavancin for SSTI, including MRSA.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8982769/

Kimyrsa, An Oritavancin-Containing Product: Clinical Study ... A new formulation of oritavancin was developed to reduce intravenous infusion volume (from 1000 mL to 250 mL), shorten infusion time (from 3 hours to 1 hour),

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03761953

Oritavancin for Staphylococcus Aureus Infections in Opioid ... This will be an early phase, single center, open label pilot study of 15 participants designed to evaluate the effects of oritavancin in patients with Opioid ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12015887/

Common Bacterial Infections in Persons Who Inject Drugs - PMC As such, outcomes associated with these infections can be poor. Healthcare providers can address these disparities through optimal ...

5. kimyrsa.com kimyrsa.com/clinical-studies/

Clinical Study Data The efficacy of KIMYRSA® has been established from adequate and well-controlled trials of another oritavancin product, ORBACTIV ®, in patients with ABSSSI. Two ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10010140/

Kimyrsa and Orbactiv – A Tale of Two Formulations - PMC 14 The purpose of this review is to evaluate the efficacy and safety data for the NF. Clinical Efficacy and Safety of Oritavancin. Oritavancin ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05599295

Study to Evaluate the Safety of Intravenous Oritavancin for ... This protocol describes a randomized, open-label study to evaluate the safety and tolerability of 2 formulations of single-dose intravenous (IV) oritavancin ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/214155s005lbl.pdf

KIMYRSA® (oritavancin) for injection, for intravenous use ... data on KIMYRSA use in pregnant women to evaluate for a drug- associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In.

9. kimyrsa.com kimyrsa.com/wp-content/uploads/2025/06/Clinical-Profile-and-RWE.pdf

DIFFERENTLY Serious hypersensitivity reactions, including anaphylaxis, have been reported with the use of oritavancin products. Discontinue infusion if signs of acute ...

10. academic.oup.com academic.oup.com/ofid/article/12/7/ofaf333/8161185

Oritavancin for the Treatment of Staphylococcus aureus ... Oritavancin is promising as a suitable and potentially cost-effective alternative for patients with SAB who are ineligible for OPAT.