Antimicrobial Therapy for Infections

(LANTERN Trial)

Recruiting at 9 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Ondine Biomedical Inc.

Disqualifiers: Pregnancy, Recent surgery, Infection, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a Phase 3 multi-center, group-randomized, crossover trial to compare nasal antimicrobial photodisinfection therapy (aPDT) with standard of care for prevention of surgical site infections in patients undergoing major elective, urgent, or emergent surgeries in a hospital setting. The main outcomes are to: 1. compare the efficacy, and 2. estimate the safety of applying nasal (aPDT) before surgery in reducing the incidence of SSIs within the initial 30 days after surgery compared to standard of care (SOC). Participants in the intervention group will receive aPDT prior to surgery on the day of surgery. Participants in the control group will receive standard of care surgical site prevention measures prior to surgery.

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 data supports the effectiveness of the treatment Nasal Antimicrobial Photodisinfection Therapy?

Research shows that antimicrobial photodynamic therapy (aPDT) can effectively kill bacteria and fungi, including those resistant to antibiotics, by using light and a special chemical to produce reactive oxygen species that destroy cells. Studies have demonstrated that aPDT can reduce bacteria and fungi by over 99.9% in models of chronic rhinosinusitis, suggesting it could be effective for nasal infections. ^{1 2 3 4 5}

Is Nasal Antimicrobial Photodisinfection Therapy generally safe for humans?

The safety of antimicrobial treatments, including newer ones, has been evaluated in clinical trials, showing they are generally safe with low rates of patients stopping treatment. However, some unique side effects can occur, especially with long-term use, and it's important for healthcare providers to recognize and manage these. ^{6 7 8 9 10}

How is Nasal Antimicrobial Photodisinfection Therapy different from other treatments for infections?

Nasal Antimicrobial Photodisinfection Therapy is unique because it uses light-activated molecules to produce reactive oxygen species that kill microorganisms, making it effective against bacteria, fungi, and viruses without relying on antibiotics. This approach is particularly useful for treating infections that are resistant to traditional antibiotic treatments. ^{2 3 4 5 11}

Research Team

Simon Sinclair, MD, PhD

Principal Investigator

Ondine Biomedical

Eligibility Criteria

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 18 years old or older.

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

I can follow all study instructions and attend all visits.

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

Trial Timeline

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

Treatment Details

Interventions

• Nasal Antimicrobial Photodisinfection Therapy (Virus 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.

Participant Groups

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+

Findings from Research

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]

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]

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 (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]

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]

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]

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]

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]

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

[In-vitro study of photodynamic therapy of antibiotic-resistant staphylococcus from patients with chronic rhinosinusitis]. [2018]

2. England pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

Photodynamic therapy of antibiotic-resistant biofilms in a maxillary sinus model. [2022]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Antimicrobial photodynamic therapy: current view]. [2007]

5. Switzerland 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. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Adverse drug reactions profile of antimicrobials: A 3-year experience, from a tertiary care teaching hospital of India. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Evaluation of safety and tolerance in clinical trials with antimicrobial agents. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Safety of newer parenteral antibiotics. [2023]

9. England pubmed.ncbi.nlm.nih.gov

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

10. France pubmed.ncbi.nlm.nih.gov

[Pilot study evaluating the ratio of adverse drug reactions related to antimicrobials over their consumption in 2012-2013]. [2017]

11. Italy pubmed.ncbi.nlm.nih.gov

Antimicrobial effects of photodynamic therapy. [2019]