Antimicrobial Therapy for Infections

(LANTERN Trial)

Recruiting at 16 trial locations

Overseen By Simon Sinclair, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ondine Biomedical Inc.

Disqualifiers: Pregnancy, Recent surgery, Infection, 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: 1 day

4514 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a new nasal treatment, nasal antimicrobial photodisinfection therapy (aPDT), in preventing infections at surgery sites compared to standard methods. The focus is on individuals undergoing major surgeries, such as heart, spine, or breast surgeries. The trial assesses whether this nasal treatment can reduce infection rates within 30 days post-surgery and ensure its safety. Individuals undergoing major surgeries who can adhere to study instructions might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does mention that participants should not be involved in other investigational research studies within the past 30 days.

What prior data suggests that nasal antimicrobial photodisinfection therapy is safe for surgical patients?

Research has shown that nasal antimicrobial photodisinfection therapy (aPDT) is generally safe for people. Studies have found no serious side effects from this treatment. For example, one study found that aPDT was safe and effective, significantly lowering infection rates in healthcare settings. Another study showed that aPDT reduced harmful bacteria levels in 92% of patients. Overall, these findings suggest that aPDT is well-tolerated and safe for its intended use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Nasal antimicrobial photodisinfection therapy (aPDT) is unique because it uses light to kill bacteria directly in the nasal cavity, which is a common source of infection. Unlike standard surgical prevention measures that rely on antibiotics and antiseptics, this treatment employs a light-activated process to destroy pathogens, potentially reducing the risk of antibiotic resistance. Researchers are excited about aPDT because it offers a quicker, more targeted approach to preventing infections, which could lead to fewer surgical site infections and a faster recovery for patients.

What evidence suggests that nasal antimicrobial photodisinfection therapy is effective for preventing surgical site infections?

Research has shown that nasal antimicrobial photodisinfection therapy (aPDT), which participants in this trial may receive, can greatly lower infection rates. Studies have found that it can reduce infections by 40-80% in various situations, even with short treatment times. One study reported a 78% drop in infections, leading to significant cost savings. This therapy has also successfully lowered virus levels, such as those of the virus causing COVID-19, in other applications. Overall, these findings suggest that aPDT is a promising method to reduce infections after surgery. ^{1 3 6 7 8}

Who Is on the Research Team?

Simon Sinclair, MD, PhD

Principal Investigator

Ondine Biomedical

Are You a Good Fit for This Trial?

This trial is for patients scheduled for major elective, urgent, or emergent surgeries. Participants should be at risk of surgical site infections (SSIs). The study excludes individuals with specific conditions that the provided information does not detail.

Inclusion Criteria

I am willing to sign the consent form and participate in the study.

I can follow all study instructions and attend all visits.

I am having a major surgery soon, such as heart, vascular, bone, brain, or extensive breast surgery.

Exclusion Criteria

I have not had surgery in the last 30 days.

Pregnancy (current) or currently lactating. If patient is unsure of pregnancy status, a negative urine or serum pregnancy test (sensitive to 25 IU hCG) should be obtained within 14 days prior to surgery

Patient has any medical, social or psychiatric condition(s) or current substance abuse condition that, in the opinion of the investigator, would preclude the patient's ability to provide informed consent, or to comply with the study requirements

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nasal antimicrobial photodisinfection therapy (aPDT) or standard of care prior to surgery

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a 30-day post-surgery period for SSI incidence tracking

30 days

Unscheduled visits for medical assessment of suspected SSIs

Inactive Interval

An approximate 6-week inactive interval period before crossover to the alternate group

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nasal Antimicrobial Photodisinfection Therapy

Trial Overview The study tests nasal antimicrobial photodisinfection therapy (aPDT) against standard infection prevention measures before surgery. It aims to see if aPDT is more effective and safe in reducing SSIs within 30 days post-surgery.

How Is the Trial Designed?

Group I: Nasal antimicrobial photodisinfection therapy (aPDT) Experimental Treatment 1 Intervention

Nasal antimicrobial photodisinfection therapy

Group II: Standard of Care Surgical Preventions - Control Active Control 1 Intervention

Standard of Care surgical site prevention measures

Who Is Running the Clinical Trial?

Ondine Biomedical Inc.

Lead Sponsor

Trials

8

Recruited

5,700+

Published Research Related to This Trial

Photodynamic therapy (PT) is an effective new approach to combat infections, especially in cases where bacteria show resistance to wide-spectrum antibiotics.

PT has demonstrated high efficacy in treating local infections, particularly pyoinflammatory ENT diseases caused by both gram-positive and gram-negative bacteria, including those that are resistant to multiple antibiotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Antimicrobial photodynamic therapy: current view]. Pal'chun, VT., Lapchenko, AS., Lapchenko, AA., et al.[2007]

Combining antimicrobial photodynamic therapy (aPDT) with antibiotics or antifungals can enhance the effectiveness of treatments against bacteria and fungi, particularly in skin and soft tissue infections, by increasing microbial susceptibility to aPDT.

This combination approach not only helps prevent the regrowth of resistant microorganisms but also reduces the risk of developing antimicrobial resistance, making it a promising strategy in combating highly resistant strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic Therapy Combined with Antibiotics or Antifungals against Microorganisms That Cause Skin and Soft Tissue Infections: A Planktonic and Biofilm Approach to Overcome Resistances. Pérez-Laguna, V., García-Luque, I., Ballesta, S., et al.[2021]

New parenteral antimicrobials like linezolid, daptomycin, and tigecycline have been introduced in the last decade and are generally safe with low patient discontinuation rates in clinical trials.

Long-term use of these antibiotics can lead to unique toxicities and adverse events, which require clinicians to be knowledgeable about each drug's safety profile to manage and reverse these effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of newer parenteral antibiotics. Stein, GE.[2023]

Antimicrobial photodynamic therapy (aPDT) combined with antimicrobials, particularly using 5-aminolevulinic acid or phenothiazinium dyes, shows promise in treating skin and mucosal infections by reducing treatment times and drug dosages.

The mechanism of action suggests that aPDT damages microbial cell walls, enhancing the effectiveness of antimicrobial drugs, which could help combat drug resistance, although the study's limitations include a small number of heterogeneous studies and a lack of clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A combination of photodynamic therapy and antimicrobial compounds to treat skin and mucosal infections: a systematic review. [2020]

Evaluating the safety and tolerance of antimicrobial agents in clinical trials is complex due to both pharmacological side effects and microbiologically induced reactions that can occur in patients.

The review proposes a systematic approach to assess cause/effect relationships and severity of adverse drug reactions, highlighting the need for improved methods in registering and classifying these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of safety and tolerance in clinical trials with antimicrobial agents. Lode, H., Stahlmann, R.[2019]

Antimicrobial photodynamic therapy (aPDT) was shown to effectively reduce antibiotic-resistant polymicrobial biofilms, including Pseudomonas aeruginosa and MRSA, by over 99.99% in an in vitro model of the maxillary sinus.

This study highlights aPDT as a promising noninvasive treatment option for chronic rhinosinusitis (CRS) patients who do not respond to traditional therapies, demonstrating its potential to target difficult-to-treat biofilms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy of antibiotic-resistant biofilms in a maxillary sinus model. Biel, MA., Pedigo, L., Gibbs, A., et al.[2022]

Photodynamic therapy (PDT) using 5-Aminolevulinic acid (ALA) and a 633 nm LED light was effective in significantly reducing multi-antibiotic-resistant Staphylococcus aureus and Staphylococcus epidermidis in vitro, with notable reductions in bacterial counts compared to control groups.

The study involved 45 chronic rhinosinusitis patients, and while PDT showed promise against antibiotic-resistant strains, further research is needed to assess potential damage to nasal mucosa and the treatment's effectiveness in live patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[In-vitro study of photodynamic therapy of antibiotic-resistant staphylococcus from patients with chronic rhinosinusitis]. Zhao, K., Yang, C., Ding, G., et al.[2018]

Over a 3-year period, 392 out of 2,586 recorded adverse drug reactions (ADRs) were attributed to antimicrobials, indicating a significant health concern, particularly with intravenous administration (53.32% of ADRs).

The most common ADR was rash, with ceftriaxone being the leading antibiotic responsible for these reactions (35.71%), and the majority of ADRs were moderate in severity (89.79%), highlighting the need for careful monitoring and intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions profile of antimicrobials: A 3-year experience, from a tertiary care teaching hospital of India. Tandon, VR., Sharma, S., Khajuria, V., et al.[2022]

Antimicrobials are a leading cause of adverse events in hospitals, prompting a focus on patient safety and the establishment of subcommittees to address these issues.

Emerging antimicrobials, such as ceftobiprole and telavancin, will soon be available, making it crucial to understand their potential harms, including Clostridium difficile infections and resistance development, as well as beta-lactam specific adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An overview of harms associated with beta-lactam antimicrobials: where do the carbapenems fit in? Owens, RC.[2021]

Antimicrobial photodynamic therapy (aPDT) uses light-activated photosensitizing molecules to generate reactive oxygen species that can effectively destroy a wide range of microorganisms, including bacteria, fungi, parasites, and viruses.

In dermatology, aPDT has shown promising results in treating various skin infections, such as chronic ulcers, acne, and leishmaniasis, making it a potential alternative treatment as antibiotic resistance increases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antimicrobial effects of photodynamic therapy. Pérez-Laguna, V., García-Malinis, AJ., Aspiroz, C., et al.[2019]

During a one-year study at a mother-child hospital, 17.5% of adverse drug reactions (ADRs) were linked to antimicrobials, highlighting the need for careful monitoring of these medications.

Five specific antimicrobials—piperacillin, valganciclovir, ceftriaxone, acyclovir, and liposomal amphotericin B—were identified as having significantly higher rates of ADRs, suggesting they should be prioritized in risk management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pilot study evaluating the ratio of adverse drug reactions related to antimicrobials over their consumption in 2012-2013]. Bérard, C., Cerruti, L., Cotteret, C., et al.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06702878

Light-Activated Antimicrobial Therapy to Prevent Surgical ... The main outcomes are to: compare the efficacy, and; estimate the safety of applying nasal (aPDT) before surgery in reducing the incidence of SSIs within the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10229198/

Impact of nasal photodisinfection on SARS-CoV-2 infection ... This study suggests nasal photodisinfection provides safe and effective COVID viral suppression when deployed across the majority of workers in an industrial ...

3. ondinebio.com ondinebio.com/78-reduction-in-infection-rates-using-nasal-photodisinfection-therapy/

78% Reduction in Infection Rates Using Nasal ... Study authors estimated 53 infections were avoided per year, at an annual cost savings of $4.24 million. Use of nasal photodisinfection was not ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1572100023001783

Nasal photodisinfection in an industrial workplace for ... This treatment has proven safe and effective, with infection rate reductions of 40-80% in tertiary care systems despite only requiring 4 minutes of therapy [2].

5. nature.com nature.com/articles/s41598-022-18513-0

Translational feasibility and efficacy of nasal photodynamic ... MB-aPDT is a safe, easily delivered and effective front-line technique that can reduce local SARS-CoV-2 viral load.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06702878

Light-Activated Antimicrobial Therapy to Prevent Surgical ... The main outcomes are to: compare the efficacy, and; estimate the safety of applying nasal (aPDT) before surgery in reducing the incidence of SSIs within the ...

7. academic.oup.com academic.oup.com/ofid/article/8/Supplement_1/S354/6450081

504. Case SEries: Nasal Antimicrobial Photodisinfection ... Results demonstrated APDT was capable of significant and rapid viral load reduction in COVID-19 carriers. 100% of patients were converted from ...

8. ondinebio.com ondinebio.com/ondine-reports-successful-us-phase-2-trial-data/

Ondine reports successful US Phase 2 trial data Results from the study showed that nasal photodisinfection eliminated or significantly decreased S. aureus in 92% of carriers (P<0.001) ...