Evaluation of Safety and Efficacy of Phage Therapy for Drug-resistant Bacterial Infections: An Exploratory, Prospective Single-arm Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 6
- 主要终点
- Pathogen Clearance Rate
研究概览
简要总结
This study is an investigator-initiated, single-center, exploratory clinical trial designed to evaluate the safety and efficacy of phage therapy in patients with urinary tract infections caused by drug-resistant bacteria.
Eligible patients aged 18 to 65 years will receive the phage cocktail intervention according to a predefined dosage regimen, with a treatment course of 2 to 3 days and a follow-up period of 2 to 4 weeks after treatment. The primary outcome measures include the incidence of adverse events during treatment, the pathogen clearance rate, and the improvement of clinical symptoms (e.g., fever, local inflammation).
The purpose of this study is to provide a scientific basis for the subsequent clinical application of this phage cocktail, and to explore a novel therapeutic option for patients with drug-resistant bacterial infections who have shown poor responses to conventional antibiotic therapy. All participants will undergo standardized medical monitoring throughout the trial, and their rights and safety will be fully protected by the Institutional Review Board (IRB) during the entire process.
详细描述
This is an investigator-initiated, prospective, single-arm exploratory clinical study conducted at the Department of Infectious Diseases, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School. The study aims to systematically evaluate the safety and efficacy of personalized phage cocktail therapy in patients with urinary tract infections (UTIs) caused by drug-resistant bacteria, addressing the unmet clinical need for alternative treatments amid the global spread of antibiotic resistance.
- Study Rationale Global mortality associated with drug-resistant bacterial infections reached 4.95 million in 2019, with 1.27 million deaths directly attributed to this cause. Projections indicate this number could rise to 10 million annually by 2050 without effective interventions. The development of new antibiotics lags far behind the emergence of drug-resistant strains, as most newly approved agents are derivatives of existing antibiotics with established resistance mechanisms. Phage therapy, leveraging the natural specificity of bacteriophages to lyse target bacteria without harming human cells or the commensal microbiota, has emerged as a promising alternative. Clinical evidence from over 6,300 global cases and systematic reviews confirms its favorable safety profile (7.5% adverse event rate vs. 14.9% for conventional antibiotics) and efficacy (78.8% clinical improvement rate, 86.7% pathogen clearance rate). This study builds on these findings to validate the clinical applicability of personalized phage therapy for drug-resistant UTIs.
- Study Design and Scope
- Study Type: Prospective, single-arm, exploratory study without a control group (justified by ethical considerations and the lack of standardized control protocols for novel phage therapy).
- Sample Size: 6 eligible patients (determined based on prior clinical data and institutional capacity).
- Study Period: Each participant undergoes a screening period (≤7 days), a treatment period (2-3 days), and a follow-up period (2-4 weeks), with a total observation duration of up to 5 weeks.
- Study Site: Department of Infectious Diseases, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School (Nanjing, China).
- Eligibility Criteria 3.1 Inclusion Criteria
- Aged 18-65 years old.
- Patients with urinary tract infections caused by drug-resistant bacteria (based on drug susceptibility test results from our hospital or other Grade A tertiary hospitals).
- The pathogenic bacteria infected by the patient must meet one of the following conditions:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Aged 18-65 years old.
- •Patients with urinary tract infections caused by drug-resistant bacteria (based on drug susceptibility test results from our hospital or other Grade A tertiary hospitals).
- •3. The pathogenic bacteria infected by the patient must meet one of the following conditions:
- •Pathogenic bacteria are resistant to key antibiotics:
- •① Acinetobacter baumannii: carbapenem-resistant;
- •Enterobacteriaceae (e.g., Klebsiella pneumoniae, Escherichia coli): carbapenem or cephalosporin-resistant;
- •Pseudomonas aeruginosa: carbapenem-resistant;
- •Enterococci: vancomycin-resistant; ⑤ Staphylococcus aureus: methicillin or vancomycin-resistant; ⑥ Stenotrophomonas maltophilia. Referenced to the WHO Bacterial Priority Pathogens List, 2024
- •The pathogenic bacteria are sensitive to key antibiotics in vitro, but treatment with such antibiotics is ineffective or shows insignificant efficacy (the patient's target bacterial infection persists for 7 days or more, and the infection cannot be eradicated despite antibiotic administration during this period).
- •The use of key antibiotics to which the pathogenic bacteria are sensitive is restricted (e.g., potential organ toxicity caused by the antibiotics, or the patient is allergic to such antibiotics).
- •4. At least one lytic phage targeting the pathogenic bacteria can be screened out.
- •5. The patient can tolerate the procedures of intravesical perfusion via urinary catheter, retrograde pyeloperfusion via ureteral catheter, or pyeloperfusion via percutaneous nephrostomy tube, and agrees to receive indwelling or intermittent catheterization during the treatment period.
- •6. The subject and their family members (or legal guardian) have fully read and understood the relevant information, and signed the informed consent form.
排除标准
- •1. Bacterial infection controllable with conventional antibiotic therapy.
- •Presence of undrained urinary tract abscess or obstruction.
- •Severe renal impairment (eGFR <30 mL/min/1.73m²).
- •Concurrent organ failure (heart, liver, lung, etc.).
- •Severe autoimmune diseases.
- •No available phages active against the infecting pathogen.
- •Other conditions deemed unsuitable by the investigator.
研究组 & 干预措施
Personalized Phage Cocktail Therapy for Drug-Resistant Urinary Tract Infections
This arm enrolls eligible patients with drug-resistant bacterial urinary tract infections (UTIs). The core intervention is personalized phage cocktail therapy, tailored to each patient's isolated drug-resistant pathogen (e.g., carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa; vancomycin-resistant Enterococcus; methicillin-resistant Staphylococcus aureus; Stenotrophomonas maltophilia).
Key Details of the Intervention:
1. Phage Cocktail Preparation: Target pathogens isolated from patients' urine samples undergo in vitro lytic phage matching via double-layer agar plate assay or liquid killing curve assay. The cocktail is formulated using lytic phages screened from a high-quality phage library (provided by Chuangshiji (Shanghai) Biotechnology Co., Ltd.), following the group standard T/SHPPA 028-2024 (Quality Requirements for Clinical Therapeutic Bacteriophage Preparations). Each batch is purified and packaged in GMP-compliant facilities, with a s
干预措施: Personalized Phage Cocktail (Biological)
结局指标
主要结局
Pathogen Clearance Rate
时间窗: Baseline (pre-treatment); Days 1, 3, 5, 7 post-treatment
次要结局
未报告次要终点