Establishing Personalized Phage Therapy and Its Comparative Cost in Difficult-to-treat Infections
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Disease-free period
研究概览
简要总结
EPHICACI is a multicenter, prospective study that continues and expands the monocentric PHAGEFORCE registry initiated at UZ Leuven. In Belgium, phage therapy can be applied as standard-of-care only in patients with difficult-to-treat infections where no curative antibiotic and/or surgical alternatives are available ('last-resort cases'). A multidisciplinary phage task force, the Coordination group for Bacteriophage therapy Leuven (CBL), evaluates eligible patients, tests pathogen susceptibility, and sets up standardized treatment protocols. With EPHICACI, this approach is extended to multiple Belgian expert centers to increase patient enrollment while upholding stringent eligibility criteria. The study aims to gain insight into the safety, efficacy, biodistribution and mechanisms of action of phage therapy, and to optimize its use across five medical disciplines (with distinct routes of administration). In addition, EPHICACI integrates machine learning-based phage-bacteria interaction analyses to guide personalized phage selection, and includes health economic evaluations to support evidence-based implementation and reimbursement strategies.
详细描述
Patients with difficult-to-treat musculoskeletal infections, chronic rhinosinusitis, persistent bacteremia, pulmonary infections associated with cystic fibrosis or bronchiectasis, or hidradenitis suppurativa, for whom no standard (curative) treatment options are available, are eligible for phage therapy. Patient eligibility is assessed by the multidisciplinary Coordination group for Bacteriophage therapy Leuven (CBL), in collaboration with multiple Belgian expert centers. If phages with activity against the isolated bacterial strain are identified and the patient meets all inclusion criteria, a phagogram is performed. Based on these results, patients are either assigned to receive phage therapy or remain in the control group receiving best available non-curative treatment. In both groups, standardized clinical, microbiological and health economic data are collected prospectively using REDCap.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with an MSI or CRS or persistent bacteremia or pulmonary infection (cystic fibrosis/bronchiectasis) or HS and
- •For whom all previous treatments (surgical and antibiotic) have failed or for whom no other treatment options are available (i.e., last resort cases, based on the assessment of the local phage hub), for example in case of bacterial resistance. And
- •Of whom the pathogen causative for the infection is one for which phages are available in the phage bank, and
- •Who have given informed consent to have their data collected in a patient registry
排除标准
- •All patients:
- •With an infectious disease other than those mentioned above, and/or
- •For whom standard treatment alternatives are still available. And/or
- •Of whom the pathogen causative for the infection is not one for which phages are available in the phage bank. And/or
- •Who refused to give their informed consent
研究组 & 干预措施
Phage treated group
Patients whose isolated pathogens are susceptible to the available phages and who have no alternative curative treatment options are included in the phage-treated group. The local phage hub, in consultation with the Phage Consortium, will design the phage therapy treatment plan (local, inhalation, or intravenous) on top of standard surgical and/or antimicrobial care. The treatment plan is documented in the patient's medical file. Patients undergo monitoring according to the phage therapy protocol and follow-up according to standard care for phage-treated patients.
干预措施: Prospective data collection phage therapy (Other)
Control group
Patients whose isolated pathogens are not susceptible to available phages, or for whom phage therapy is not indicated, are included in the control group. These patients receive standard surgical and/or antimicrobial care as determined by the local phage hub. Monitoring and follow-up are according to the standard of care for the underlying pathology.
干预措施: Prospective data collection standard-of-care (Other)
结局指标
主要结局
Disease-free period
时间窗: Until 1 year after treatment
In MSI patients
Smell test
时间窗: Until 1 year after treatment
16-point Sniffin' Sticks test in CRS patients
Radiological scores
时间窗: Until 1 year after treatment
Lund-Mackay CT score in CRS patients
Endoscopic scores
时间窗: Until 1 year after treatment
Lund-Kennedy score and Modified Davos score in CRS patients
Time to clearance of infection
时间窗: Until 1 year after treatment, daily during hospitalization until infection clearance
In patients with Persistent Bacteremia
Overall survival
时间窗: Until 1 year after treatment
Does the patient survive (for patients with Persistent Bacteremia)
SOFA score
时间窗: Baseeline and daily during hospitalization until discharge, for up to 12 weeks after cessation of phage therapy; thereafter at 6 months and 1 year after cessation of phage therapy.
Sequential Organ Failure Assessment (SOFA) score in patients with persistent bacteremia, assessed to monitor changes in organ dysfunction during hospitalization.
Tolerance of the intervention
时间窗: During scheduled phage therapy (up to 6 weeks)
Proportion of patients with chronic pulmonary infection able to complete the planned phage therapy without treatment discontinuation due to adverse reactions or pulmonary exacerbations.
Sputum culture conversion assessed by microbiological culture
时间窗: Days 1-4 of phage therapy, weekly during phage therapy for up to 6 weeks, and at 6 and 12 months after completion of phage therapy.
Proportion of patients with chronic pulmonary infection with conversion from a positive sputum culture for the targeted bacterial pathogen at baseline to a negative sputum culture for the targeted bacterial pathogen after phage therapy.
Within-subject change in the number of positive cultures
时间窗: At 6 and 12 months compared to 12 months prior to therapy
In patients with Chronic Pulmonary Infection
Within-subject change in the number of pulmonary exacerbations requiring additional antibiotic therapy or hospitalization.
时间窗: At 6 and 12 months
In patients with Chronic Pulmonary Infection
Clinical response measured by forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC).
时间窗: Until 1 year after treatment
In patients with Chronic Pulmonary Infection
Improvement in IHS4 score
时间窗: Until 1 year after treatment
In HS patients
Improvement in ANF count using HiSCR50 and HiSCR75
时间窗: Until 1 year after treatment
In HS patients
Reduction in flare incidence compared to the 12 weeks prior to treatment.
时间窗: Until 1 year after treatment
In HS patients
Bacterial load in sinonasal material measured by quantitative microbiological culture
时间窗: Until 1 year after treatment
Bacterial load of the targeted bacterial pathogen in sinonasal samples from CRS patients quantified by microbiological culture and expressed as colony-forming units (CFU).
次要结局
- PROMIS global health(until 1 year after treatment)
- PROMIS pain interference(until 1 year after treatment)
- PROMIS physical function(until 1 year after treatment)
- iMCQ(until 1 year after treatment)
- iPCQ(until 1 year after treatment)
- EQ-5D-5L(until 1 year after treatment)
- SNOT-22(until 1 year after treatment)
- VAS pain(until 1 year after treatment)
- CF-Q(until 1 year after treatment)
- Bronchiectasis QoL(until 1 year after treatment)
- FEV1(until 1 year after treatment)
- FVC(until 1 year after treatment)
- DLQI(until 1 year after treatment)
- HiSQoL(until 1 year after treatment)
- Systemic and local phage exposure per route of administration(until 1 year after treatment)
- Duration of phage activity in blood or locally(until 1 year after treatment)
- Change in phage-neutralizing activity measured by serum neutralization test(until 1 year after treatment)
- Change in bacterial load of the targeted pathogen measured by quantitative microbiological culture(until 1 year after treatment)