Randomized and Multicenter Clinical Trial to Evaluate the Effectiveness and Efficiency of a Voriconazole Preemptive Genotyping Strategy in Patients With Risk of Aspergillosis
试验速览
- 阶段
- 4 期
- 入组人数
- 146
- 试验地点
- 1
- 主要终点
- Serum voriconazole concentration
研究概览
简要总结
This is a phase IV pragmatic, multicentre, randomised, simple-blind, parallel arm, centre-stratified clinical trial. The main objective is to compare efficiency of voriconazole preemptive genotyping strategy, compared with routine practice.
详细描述
Primary outcome is serum level of voriconazole on fifth day. Secondary outcome is a combined variable of therapeutic failure and adverse events, associated with voriconazole. A total of 146 patients with risk of undergoing invasive aspergillosis who potentially will receive voriconazole will be recruited, and CYP2C19 will be genotyped. If the patient receives voriconazole finally, he will be randomized (1:1 experimental/control). In the experimental arm patients receive dose according to pharmacogenetic algorithm including CYP2C19 genotype and clinical and demographic information. In the control arm patients receive dose according to clinical practice guidelines. In addition, a Spain national health system (NHS) point-of-view cost-effectiveness evaluation is going to be done. Direct costs calculation of each arm will be done.
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
- Single (Participant)
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient at risk of developing invasive aspergillosis, that will potentially receive treatment or prophylaxis with voriconazole:
- •A. Pediatric population: children who are going to receive a transplant of hematopoietic precursors (HSCT) and acute myeloid leukemias, as well as relapses of it.
- •B. Adult population: patients diagnosed with acute leukemia, and those patients with expected prolonged neutropenia, secondary to hematological process and / or after specific treatment (aplastic anemia and variants, myelodysplastic syndrome, solid organ or bone marrow transplant, etc.), and those whose responsible clinician consider individually that they could present a risk of developing a fungal infection.
- •Those who agree to participate in the study by signing informed consent (patients equal or over 18 years old)
- •Subjects under 18 years old whose representative / legal guardian has voluntarily signed the informed consent.
- •In the case of mature under 18 years subjects (12-17 years of age), in addition to the consent signed by the legal guardian, the consent of the subject will be obtained.
排除标准
- •Patients who for any reason should not be included in the study according to the criteria of the research team.
- •Subjects who are not capable to understand the information sheet and unable to sign the informed consent.
研究组 & 干预措施
Experimental group
Based on the genetic study carried out and the patient's characteristics (age, weight, indication), the Pharmacogenetics Unit of the University Hospital La Paz will indicate the dose to be administered based on the therapeutic individualization protocol guided by pharmacogenetics.
干预措施: Voriconazole preemptive genotyping strategy (Drug)
Control group
No information will be provided and procedure will be carried out according to normal clinical practice, with clinical monitoring by the doctor in charge.
干预措施: Voriconazole clinical practice (Drug)
结局指标
主要结局
Serum voriconazole concentration
时间窗: Day 5 of treatment
Serum voriconazole concentration within the therapeutic range, in μg/mL.
次要结局
- Adverse event(Within 3 months)
- Costs by adverse event(Day 90 of treatment)
- Quality adjusted life years (QALY)(Day 90 of treatment)
- Therapeutic failure(Within 3 months)