A Phase 2 Study of Methylene Blue Photodynamic Therapy for Treatment of Breast Abscesses

Breast abscesses consist of a localized, walled-off collection of infected fluid within the breast, with symptoms including breast pain and inflammation, as well as nipple discharge, fever, chills, and nausea. If left untreated, breast abscesses can result in serious complications, including fistula formation and sepsis. The standard of care therefore involves draining the purulent fluid, generally under ultrasound guidance, and systemic antibiotic administration. Although this drainage procedure is typically technically successful, reported recurrence rates vary widely. These recurrent breast abscesses can require repeated drainage procedures, surgical intervention, extended hospital stays, and aggressive antibiotic regimens.

Photodynamic therapy (PDT), which relies upon the combination of photosensitive dyes known as photosensitizers, excitation by visible light, and molecular oxygen to generate bactericidal reactive oxygen species, represents a potentially powerful adjunct to standard of care drainage. The investigators have successfully completed a Phase 1 clinical trial assessing the safety and feasibility of methylene blue (MB) PDT at the time of percutaneous intra-abdominal abscess drainage. No adverse or serious adverse events were observed, and the procedure was well tolerated by all subjects. Based on the success of this Phase 1 clinical trial, the current study aims to assess efficacy of MB-PDT at the time of breast abscess drainage.

The investigators propose a randomized, controlled Phase 2 clinical trial, which will be conducted in accordance with the principles of good clinical practice and with 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 at initial presentation. Consented subjects will be prospectively randomized using block randomization to one of two arms: (1) standard of care (SOC) percutaneous drainage and antibiotics alone or (2) PDT + SOC. The primary outcome is time to resolution of clinical symptoms. The secondary outcome is imaging evidence of abscess resolution, based on ultrasound tomography. Tertiary outcomes include abscess recurrence, need for repeated intervention, and cure rate across treatment groups.

The study population will consist of 50 subjects, allocated equally between the two groups. Sample size calculations are based on a hypothesized reduction in the time to resolution of clinical symptoms. The investigators use retrospective data from patients that received SOC at our institution over the course of 15 years to represent SOC, and the 18 subjects treated in our Phase 1 clinical trial in abdominopelvic abscesses to represent PDT. Retrospective standard of care patients had median time to resolution of 16 days (95% CI 14-18 days), while subjects treated with MB-PDT had a median time to resolution of 7 days (95% CI 3-14 days). This corresponds to a hazard ratio for resolution of symptoms of 3.5. The investigators target 90% power at a more conservative hazard ratio of 3.0 to determine the sample size in each arm. A sample size of 25 subjects per arm provides 90% power to detect a hazard ratio of 3.0 at a two-sided alpha=0.05 level of significance. With equal allocation between groups, this results in a total sample size of 50 participants, given that the investigators assume to fully observe the primary outcome in all subjects.

All subjects will receive standard of care ultrasound-guided percutaneous breast abscess drainage. The site will be prepared and dressed following standard of care sterile procedure, and a needle will be advanced under ultrasound guidance into the abscess. The abscess will be drained by syringe aspiration, and the cavity will be flushed with sterile saline. Aspirated abscess fluid will be delivered to the Clinical Microbiology Laboratory for processing.