PIVOTAL: Pharmacological Individualisation of VOriconazole Therapy for AntifungaL Treatment
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 发起方
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Dose adjustment success
研究概览
简要总结
This is a trial to determine whether giving a patient a tailored dose of voriconazole is safe and effective.
详细描述
Invasive fungal infections are a major cause of morbidity and mortality in patients with haematological malignancy and haematopoietic stem cell transplantation.
Voriconazole is routinely used as a first-line agent for the treatment of invasive aspergillosis, invasive fusariosis and scedosporiosis. Voriconazole has extreme pharmacokinetic variability. Adult patients with a trough concentration of < 1 mg/L have a lower probability of clinical response whereas patients with trough concentrations > 6 mg/L a higher probability of toxicity.
Therapeutic drug monitoring for dose adjustment is advocated but there are no algorithms that enable voriconazole dosage to be reliably adjusted to achieve desired trough concentrations in a timely and optimally precise manner.
Novel ways to deliver optimised antifungal therapy are urgently required and this trial will evaluate whether giving a patients a tailored dose of voriconazole is safe and effective.
Plasma concentrations will be taken in real time and inputted in dose software that will calculate an optimum dose for the required trough concentration of 1-3 mg/L.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Any adult ≥18 years old
- •Patients where a new course of voriconazole is indicated for suspected or confirmed invasive aspergillosis or other serious fungal infections that is deemed by the treating physician to be susceptible to voriconazole
- •Patients must have venous access to permit the administration of voriconazole and enable the procurement of multiple plasma samples to measure voriconazole concentrations.
- •Estimated creatinine clearance ≥ 50 mL/min
- •Able to give written informed consent
- •Considered fit to receive the trial treatment
- •Able to remain in the hospital for at least 5 days or until they complete their trial treatment
- •Female patients must satisfy the investigator that they are not pregnant, or are not of childbearing potential, or are using adequate contraception
- •Men must also use adequate contraception
排除标准
- •Patients with an estimated creatinine clearance < 50 mL/minute (this precludes the use of intravenous voriconazole)
- •Patients receiving any form of renal replacement therapy i.e. haemodialysis or haemofiltration
- •Patients with hepatic insufficiency
- •Female patients that are pregnant, breast feeding or planning pregnancy during the study
- •Past history of intolerance to voriconazole
- •Evidence of a clinically relevant fungal isolate that is resistant to voriconazole
- •QT prolongation on ECG
- •Use of other medications that contraindicate the use of voriconazole
- •Patients receiving any other medications that are contraindicated with the use of voriconazole i.e. terfenadine, long acting barbiturates, ergot alkaloids, etc. (Refer to SMPC). Only patients on rifampicin, rifabutin, phenytoin, and carbamazepine would have voriconazole precluded. Voriconazole influences with the pharmacokinetics of many additional agents- (see SMPC)- most importantly anti-rejection compounds- cyclosporine, tacrolimus]
- •Uncontrolled cardiac, respiratory or other disease or any serious medical or psychiatric disorder that would preclude trial therapy or informed consent.
- •Hypersensitivity to Voriconazole, its excipients or other triazoles
研究组 & 干预措施
Voriconazole
Standard adult Voriconazole (VFEND) Loading (1 hr infusion): 6mg/kg at 1 hour and 12 hours on day 1. Followed by standard maintenance dose 4mg/kg at 1 hour and 12 hours on day 2 (1 hour infusion). Day 3 follows the same schedule, expect the dose is adjusted, this dose is used on Day 4 and a further dose adjustment is made that is administered as above on Day 5.
干预措施: VFEND (Drug)
结局指标
主要结局
Dose adjustment success
时间窗: Day 5 of treatment
Dose adjustment success will be evaluated by plasma trough concentration on day 5, successful dose adjustment is defined as a trough concentration of 1-3 mg/L of voriconazole.
次要结局
- Mortality of patients(35 Day after starting treatment)
- Toxicity(Day 5 of treatment and 35 day follow-up)
研究者
Brynn Chappell
Clinical Trials Project Manager
The Christie NHS Foundation Trust