A Phase 2 Study to Assess Efficacy of Methylene Blue Photodynamic Therapy for Treatment of Deep Tissue Abscesses
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Time to removal of the drainage catheter
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Investigator, Outcomes Assessor)
盲法说明
The subject and study doctor will not be masked to group assignment, as it would be difficult or impossible to do so and unethical to subject patients to sham procedures if they are not assigned to a PDT group. However, all follow-up and subsequent data collection will be performed by a member of the study team that is masked to group assignment. Group assignment will only be unmasked to the study biostatistician at the time of statistical analysis. The remainder of the study team will only be unmasked after final results are published. This will reduce the potential for bias in collection of follow-up data, and protect the integrity of the study.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
MB-PDT at pre-defined dose plus standard of care abscess drainage
Each subject in this arm will receive standard of care abscess drainage, methylene blue, lipid emulsion, and laser illumination at an optical power defined by their abscess size.
干预措施: Methylene Blue (Drug)
MB-PDT at pre-defined dose plus standard of care abscess drainage
Each subject in this arm will receive standard of care abscess drainage, methylene blue, lipid emulsion, and laser illumination at an optical power defined by their abscess size.
干预措施: Lipid Emulsion (Drug)
MB-PDT at pre-defined dose plus standard of care abscess drainage
Each subject in this arm will receive standard of care abscess drainage, methylene blue, lipid emulsion, and laser illumination at an optical power defined by their abscess size.
干预措施: Insertion of optical fiber (Device)
MB-PDT at pre-defined dose plus standard of care abscess drainage
Each subject in this arm will receive standard of care abscess drainage, methylene blue, lipid emulsion, and laser illumination at an optical power defined by their abscess size.
干预措施: Laser Illumination (pre-defined dose) (Device)
MB-PDT at pre-defined dose plus standard of care abscess drainage
Each subject in this arm will receive standard of care abscess drainage, methylene blue, lipid emulsion, and laser illumination at an optical power defined by their abscess size.
干预措施: Standard of care abscess drainage (Procedure)
MB-PDT at patient-specific dose plus standard of care abscess drainage
Each subject in this arm will receive standard of care abscess drainage, methylene blue, lipid emulsion, optical spectroscopy, and laser illumination. The optical power for laser illumination will be determined by their abscess morphology and the results of optical spectroscopy.
干预措施: Methylene Blue (Drug)
MB-PDT at patient-specific dose plus standard of care abscess drainage
Each subject in this arm will receive standard of care abscess drainage, methylene blue, lipid emulsion, optical spectroscopy, and laser illumination. The optical power for laser illumination will be determined by their abscess morphology and the results of optical spectroscopy.
干预措施: Lipid Emulsion (Drug)
MB-PDT at patient-specific dose plus standard of care abscess drainage
Each subject in this arm will receive standard of care abscess drainage, methylene blue, lipid emulsion, optical spectroscopy, and laser illumination. The optical power for laser illumination will be determined by their abscess morphology and the results of optical spectroscopy.
干预措施: Insertion of optical fiber (Device)
MB-PDT at patient-specific dose plus standard of care abscess drainage
Each subject in this arm will receive standard of care abscess drainage, methylene blue, lipid emulsion, optical spectroscopy, and laser illumination. The optical power for laser illumination will be determined by their abscess morphology and the results of optical spectroscopy.
干预措施: Optical Spectroscopy Measurement (Device)
MB-PDT at patient-specific dose plus standard of care abscess drainage
Each subject in this arm will receive standard of care abscess drainage, methylene blue, lipid emulsion, optical spectroscopy, and laser illumination. The optical power for laser illumination will be determined by their abscess morphology and the results of optical spectroscopy.
干预措施: Laser Illumination (patient-specific dose) (Device)
MB-PDT at patient-specific dose plus standard of care abscess drainage
Each subject in this arm will receive standard of care abscess drainage, methylene blue, lipid emulsion, optical spectroscopy, and laser illumination. The optical power for laser illumination will be determined by their abscess morphology and the results of optical spectroscopy.
干预措施: Standard of care abscess drainage (Procedure)
Standard of care abscess drainage
Each subject in this arm will receive standard of care abscess drainage
干预措施: Standard of care abscess drainage (Procedure)
结局指标
主要结局
Time to removal of the drainage catheter
时间窗: Day 1 post-intervention until removal of drainage catheter
Drainage catheter output into the drainage bag will be noted daily by a member of the study team and the drainage catheter will be removed when output is reduced to \<5 mL/day, as is standard of care for this patient population. Time to drainage catheter removal (in days) will be recorded for all subjects.
次要结局
- Mean Change in bacterial burden(Pre and post intervention (approximately 24 hours))
- Total volume of catheter drainage output(day 14)
- mean number of days from intervention to symptom resolution(day 14)
研究者
Timothy Baran
Assistant Professor
University of Rochester