Universal Posaconazole Prophylaxis Versus Pre-emptive Posaconazole Therapy for Fungal Infection Management Post-lung Transplantation
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 140
- 试验地点
- 6
- 主要终点
- Composite of: screened that are eligible, eligible that are enrolled, lost to follow-up or are withdrawn from the trial, receive their allocated treatment throughout the trial participation and have missing data during trial data collection.
研究概览
简要总结
This trial will examine 2 ways of using the antifungal posaconazole to prevent invasive fungal disease and the precipitation of chronic rejection post lung transplantation.
详细描述
Lung transplantation (LT) is an increasingly used treatment for end-stage respiratory disease. However, it is expensive, with hospital costs alone estimated at >US$500,000/transplant. Fungal infection and chronic lung allograft dysfunction (CLAD) are the major complications of LT. They pose the greatest threat to long-term survival and are reported to occur in 12-50% of LT recipients and cause death in 21.7-82% of these.
Fungal infections occur in 3 major forms in LT recipients, namely colonisation, trachea-bronchial disease and invasive (or end-organ) disease. Whilst invasive fungal disease (IFD) is associated with the highest mortality, colonisation poses the greatest clinical challenge. It is the most common manifestation, can progress to IFD and can precipitate CLAD. Antifungal prophylaxis is used to minimise the risks associated with colonisation.
Two main antifungal prophylaxis strategies are used. Universal prophylaxis (UP) is defined as the administration of antifungal agents to all patients post-LT. Most centres use UP. A systematic review and meta-analysis showed neither Aspergillus colonisation nor invasive aspergillosis (IA) (the commonest fungal infection in LT recipients) were reduced by UP. Yet it caused side-effects in 29.6%.
The pre-emptive strategy is defined as the administration of antifungal agents when a fungal pathogen (including in donor specimens) is detected or there is serological evidence of a fungal pathogen in the absence of IFD from a post-LT surveillance bronchoscopy or other clinical investigations (i.e. colonisation).Observational data suggest that a pre-emptive strategy has similar IA incidence rates but fewer adverse drug reactions (ADR) than UP (16.1%). It has been estimated that a pre-emptive strategy can reduce antifungal drug use by 43%.
No direct comparison of the efficacy, safety and cost of the two strategies has been performed to date. Thus, a randomised controlled trial (RCT) is needed to determine the optimal strategy to reduce the impact of fungal infection in LT recipients. However, before we embark on a definitive phase III RCT powered for clinical outcomes we will perform a pilot feasibility RCT to generate data and answer practical questions to better inform the design of the definitive phase III RCT powered for clinical outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
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
- •Male and female aged ≥ 18 years
- •Undergoing bilateral sequential lung transplant (BSLT) or heart-lung transplant (HLT) including re-do transplant
- •Able to give written informed consent
- •Able to understand and comply with all trial requirements
排除标准
- •Less than 18 years of age
- •Scheduled to undergo a single-lung transplant (known risk factor for IFD)
- •Scheduled to undergo multi-organ transplant, other than HLT
- •Recipients who will not be followed up for 1-year post-transplant at one of the trial sites
- •Isolation of a mould within the 12 months prior to screening
- •Evidence of a mycetoma within the 12 months prior to screening
- •Proven or probable IFD within the 12 months prior to screening
- •Patients with moderate or severe liver disease as defined by aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times the upper limit of normal (ULN)
- •Any other severe condition which in the site investigator's judgement may interfere with the trial evaluations or severely affect the patients safety
- •Previous inclusion in the trial
- •Currently enrolled in an antifungal or other investigational drug trial
研究组 & 干预措施
Universal posaconazole prophylaxis
Universal posaconazole prophylaxis: All patients will start posaconazole modified release tablet (300mg daily ) between Day 4 and Day 14 post lung or heart-lung transplantation for 3 months.
干预措施: Universal Posaconazole Prophylaxis (Other)
Pre-emptive posaconazole therapy
Pre-emptive posaconazole therapy: Posaconazole will be started if a fungal pathogen is identified or there is serological evidence of a fungal pathogen in the absence of any evidence of invasive fungal disease and given for 3 months.
干预措施: Pre-emptive Posaconazole Therapy (Other)
结局指标
主要结局
Composite of: screened that are eligible, eligible that are enrolled, lost to follow-up or are withdrawn from the trial, receive their allocated treatment throughout the trial participation and have missing data during trial data collection.
时间窗: 2 years and 3 months
Feasibility outcome
次要结局
- CLAD rates(2 years and 3 months)
- All-cause mortality rates(2 years and 3 months)
- Fungal pneumonia, fungal tracheobronchitis, or bronchial anastomotic fungal infection-related mortality rates(2 years and 3 months)
- CLAD-related mortality rates(2 years and 3 months)
- Time to development of fungal pneumonia, fungal tracheobronchitis, bronchial anastomotic fungal infection(2 years and 3 months)
- Time to diagnosis of CLAD(2 years and 3 months)
- Costs associated with allocated arm including number of hospital admissions(2 years and 3 months)
- Quality of life (QoL) using Short Form Survey (sf-36) to measure patient health(2 years and 3 months)
- Acute rejection rates(2 years and 3 months)
- Posaconazole adverse drug reaction (ADR) rates(2 years and 3 months)
- Proportion of patients who discontinue posaconazole because of an ADR(2 years and 3 months)
- Total duration on posaconazole(2 years and 3 months)
- Composite of: at least one episode of fungal pneumonia, fungal tracheobronchitis, or bronchial anastomotic fungal infection; diagnosed as having CLAD or died regardless of cause(2 years and 3 months)
- Fungal pneumonia, fungal tracheobronchitis, or bronchial anastomotic fungal infection rates(2 years and 3 months)