Clinical trial NCT06052956: Efficacy of Methylene Blue Photodynamic Therapy for Treatment of Deep Tissue Abscesses
Official title: A Phase 2 Study to Assess Efficacy of Methylene Blue Photodynamic Therapy for Treatment of Deep Tissue Abscesses
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Abscess
Keywords: Abscess
Drainage
Photodynamic Therapy
Lead sponsor: University of Rochester
Sponsor class: OTHER
First posted: 2023-09-25
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study includes three arms: (1) MB-PDT at a fixed drug/light dose plus standard of care abscess drainage, (2) MB-PDT at a patient-specific dose determined by pre-treatment optical measurements plus standard of care abscess drainage, and (3) standard of care abscess drainage.
Primary purpose: TREATMENT

Brief summary: The objective of this Phase 2 study is to evaluate the efficacy of methylene blue photodynamic therapy (MB-PDT) performed at the time of percutaneous abscess drainage for disinfection of deep tissue abscesses. The study includes three arms: (1) MB-PDT at a fixed drug/light dose plus standard of care abscess drainage , (2) MB-PDT at a patient-specific dose determined by pre-treatment optical measurements plus standard of care abscess drainage , and (3) standard of care abscess drainage. The primary endpoint is reduction in time to removal of the drainage catheter.

Detailed description: Abscesses form as a result of the interaction between an acute microbial infection and the host immune system, and generally result in fever, nausea, and acute abdominal pain. If untreated, the mortality rate can be high. Abscesses are routinely managed by image-guided percutaneous drainage and delivery of systemic antibiotics. Despite this standard of care, abscesses remain a significant source of morbidity, mortality, and hospital stay. Further, response can vary widely between patients. Many abscesses also contain antibiotic resistant species.

Photodynamic therapy (PDT), which relies upon the combination of photosensitive dyes known as photosensitizers, excitation by visible light, and molecular oxygen to generate cytotoxic reactive oxygen species, represents a powerful adjunct to standard of care drainage. A Phase 1 clinical trial aimed at assessing the safety and feasibility of methylene blue (MB) PDT at the time of percutaneous abscess drainage (ClinicalTrials.gov Identifier: NCT02240498) was completed. No adverse or serious adverse events were observed, and the procedure was well tolerated by all subjects. Based on these encouraging Phase 1 results, the current study therefore aims to assess efficacy of MB-PDT by quantification of time to removal of the drainage catheter and microbiological analysis of pre- and post-PDT aspirate samples.

This is a single center, randomized, open-label Phase 2 clinical trial, which will be conducted in accordance with the principles of good clinical practice and following approval by both the FDA and local IRB. Patients who have been diagnosed with a drainable abscess, that meet all inclusion/exclusion criteria, and have the approval of their primary care team, will be offered enrollment in the study. Consented subjects will be assigned prospectively to one of three arms: (1) MB-PDT at a fixed drug/light dose plus standard of care abscess drainage, (2) MB-PDT at a patient-specific dose determined by pre-treatment optical measurements plus standard of care abscess drainage, and (3) standard of care abscess drainage alone. The primary endpoint is time to removal of the drainage catheter. The secondary endpoint is reduction in bacterial burden from pre- to post-intervention. Tertiary endpoints include drain output following intervention, resolution of clinical symptoms, abscess recurrence, need for repeated intervention, and cure rate.

All subjects will receive standard of care image-guided percutaneous abscess drainage. This includes collection of a pre-intervention abscess aspirate sample, and placement of a drainage catheter.

For subjects in Arms 1 and 2, sterile methylene blue (MB) will then be administered to the abscess cavity using the same needle/catheter utilized for standard of care drainage. After a 10 minute incubation interval, MB will be aspirated and the cavity flushed with sterile saline.

For subjects in Arm 2, optical spectroscopy measurements will then be made to determine the optical properties of the abscess wall. This will be done by connecting the proximal end of the sterile optical fiber used for treatment illumination to a custom optical spectroscopy system. The distal end of this fiber will be advanced through the same catheter/needle used for the standard of care procedure in order to make gentle contact with the wall of the cavity. Low-intensity white light will be delivered by the fiber, and light that has interacted with the abscess wall will be detected by the same optical fiber. These optical measurements will be averaged and used to extract the absorption and reduced scattering coefficients at the treatment wavelength. These extracted optical properties, along with the subject's segmented pre-procedure CT images, will be used to generate a patient-specific treatment plan that seeks to deliver a desired fluence rate to 95% of the abscess wall, while limiting the portion of the abscess wall that receives a high fluence rate (\>400 mW/cm2) to less than 5%.

For subjects in Groups 1 and 2, the cavity will then be filled with sterile 0.1% lipid emulsion solution to gently distend the cavity, and through efficient light scattering, homogenize the light dose to the walls of the cavity. A sterile optical fiber will be advanced to the approximate center of the abscess cavity via the same catheter/needle under image guidance. The proximal end of the fiber is coupled to the output of a diode laser system emitting light at 665 nm.

For subjects in Group 1 (MB-PDT at a fixed dose), laser power will be delivered to the cavity at a constant fluence rate. The laser power required to obtain the desired fluence rate at the wall will be calculated purely based on the abscess size. For subjects in Group 2 (MB-PDT with patient-specific treatment planning), the subject's measured optical properties and their segmented pre-procedure CT images will be integrated with treatment planning software to determine the laser power required to deliver the desired fluence rate to 95% of the abscess wall, while limiting the portion of the abscess wall that receives a fluence rate of \>400 mW/cm2 to less than 5%. In both cases, illumination will be delivered for 20 minutes, resulting in a total delivered fluence of 24 J/cm2. Immediately after laser irradiation, the Intralipid solution will be aspirated and the cavity again flushed with sterile saline.

Collection of aspirated abscess material for microbiological assessment is standard of care for percutaneous abscess drainage. A portion of this standard of care collection will be collected by the study team for additional quantitative evaluation. Additionally, a post-intervention aspirate sample will be collected for study purposes.

If successful, this research could result in an adjunct treatment for abscess patients that improves long-term abscess resolution and the rate of response to percutaneous drainage. This clinical strategy would offer a wide range of potential health benefits to patients with deep tissue abscess. Among these advantages are reduced surgical intervention, decreased spread of infection, shortened course of post-treatment antibiotic therapy, and decreased selective pressure for antibiotic resistance. Ultimately, this would promote early recovery, shorten hospital stay, and lead to lower overall health care costs for patients undergoing image-guided percutaneous abscess drainage.

Eligibility criteria: Inclusion Criteria:

* Adults 18 years or older
* All patients with clinical symptoms (ex: fever, chills, pain, tachycardia, hypotension), laboratory (leukocytosis) and radiologic findings (thick walled, rim-enhancing collection with gas bubbles or air-fluid levels) compatible with an abscess that requires image- guided percutaneous drainage
* Approval by the primary care team to pursue PDT and discuss enrollment with the patient

Exclusion Criteria:

* Pregnancy
* Lactation
* Allergy to contrast media, narcotics, sedatives, atropine or eggs
* Necrotic tissue that requires surgical debridement
* Severely compromised cardiopulmonary function or hemodynamic instability
* Thrombocytopenia (\<50,000/mm3)
* Uncorrectable coagulopathy
* Poor kidney function (serum creatinine \>3mg/dl)
* Lack of a safe pathway to the abscess or fluid collection
* Unable or unwilling to understand or to provide informed consent
* Unable or unwilling to undergo study procedures
* Patient unable to cooperate with, or to be positioned for the procedure
* Unable to comply with necessary follow up
* Patients with pancreatic abscesses
* Patients with known fistulous communication with their abscess
* Abscess greater than 13 cm in diameter

Primary outcomes:
measure: Time to removal of the drainage catheter
timeFrame: Day 1 post-intervention until removal of drainage catheter
Secondary outcomes:
measure: Mean Change in bacterial burden
timeFrame: Pre and post intervention (approximately 24 hours)
measure: Total volume of catheter drainage output
timeFrame: day 14
measure: mean number of days from intervention to symptom resolution
timeFrame: day 14
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Highland Hospital
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
Study officials:
affiliation: University of Rochester
name: Timothy M Baran, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Rochester
name: Ashwani K Sharma, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Rochester
name: Laurie Christensen, BS
role: STUDY_DIRECTOR
References: