Efficacy of Itraconazole and of Voriconazole in Patients With Cystic Fibrosis and Presenting With Persistent Positive Sputums for Aspergillus.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 11
- 试验地点
- 15
- 主要终点
- Change in percentage of patients with a negativisation of sputum cultures in 2 successive samples
研究概览
简要总结
Aspergillus infection is an infectious complication which frequently occurs in cystic fibrosis. The efficacy of azole therapy in patients with cystic fibrosis with persistent positive sputums for Aspergillus is still unknown. Furthermore, the efficacy of itraconazole and voriconazole in this indication has never been evaluated in a large prospective controlled clinical trial, even though many teams already use it. The ATCF study aims to assess in patients with cystic fibrosis with persistent Aspergillus positive cultures the efficacy of itraconazole and voriconazole on the negativisation of the sputum cultures for Aspergillus.
详细描述
Aspergillus infection is an infectious complication which frequently occurs in cystic fibrosis. The efficacy of azole therapy in patients with cystic fibrosis with persistent positive sputums for Aspergillus is still unknown. Furthermore, the efficacy of itraconazole and voriconazole in this indication has never been evaluated in a large prospective controlled clinical trial, even though many teams already use it.
The ATCF study is a prospective, multicenter, randomized, open-label, controlled phase II trial, performed in patients with cystic fibrosis with persistent Aspergillus positive cultures.
The primary outcome is to assess the efficacy of itraconazole and voriconazole on the course and outcome of the negativisation of the sputum cultures for Aspergillus on two consecutive cultures.
Secondary objectives include the effects of azole therapy on quality of life, FEV1, co-prescription of antibiotic and steroids, plasma concentrations of antifungal agents, speed of negativisation of sputum culture for Aspergillus, outcome of other diagnostic criteria (Aspergillus detection by PCR, precipiting antibodies, total and specific IgE, eosinophilia), and the safety profiles of the two products. Mycological failures, and impact of anti-fungal treatments on lung and systemic inflammation will also be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with cystic fibrosis,
- •men or women,
- •age equal greater to 12 years,
- •presenting with a positive sputum culture for Aspergillus confirmed twice within 6 months before study entry and at initial visit,
- •written informed consent.
排除标准
- •patients with a contraindication to one of the antifungal agents evaluated,
- •pregnant women or nursing mothers,
- •absence of an effective method of contraception in women of child-bearing potential,
- •patients with signs or symptoms of invasive aspergillosis,
- •patients with signs or symptoms of aspergilloma,
- •patients with an infection caused by Burkholderia complex Cepacia or to mycobacteria,
- •lung transplant patients, registered on a transplantation waiting list or whose registration is imminent,
- •patients who received systemic antifungal therapy for more than 5 days within 2 months prior to inclusion,
- •patients currently enrolled in another clinical drug trial,
- •ongoing treatment with medicinal products contraindicated with itraconazole and voriconazole or with major interactions which reduce azole concentrations,
- •patients treated by medication known to prolong QT interval, or with known prolongation of QTc interval > 450 msec in men and > 470 msec in women,
- •Inability to follow or to understand the study procedures.
研究组 & 干预措施
itraconazole
- itraconazole 10 mg/mL oral solution
- patients > 40 kg body weight : 200 mg morning and evening.
- patients < 40 kg body weight : 100 mg morning and evening.
- dosage out of meal.
- Without a loading dose
干预措施: Itraconazole/voriconazole (Drug)
voriconazole
- voriconazole 40 mg/mL oral suspension :
- patients > 40 kg body weight : 200 mg morning and evening.
- patients < 40 kg body weight : 100 mg morning and evening.
- dosage out of meal.
- Without a loading dose
干预措施: Itraconazole/voriconazole (Drug)
结局指标
主要结局
Change in percentage of patients with a negativisation of sputum cultures in 2 successive samples
时间窗: Change from baseline in persentage of patients with a negativisation of sputum cultures at 4, 8, 16, 24 weeks after initiation of therapy
The primary evaluation criterion is the percentage of patients with a negativisation of sputum cultures in 2 successive samples, according to a standardised technique
次要结局
- plasma concentrations of antifungal agents(at 2 weeks after initiation of therapy)
- safety of AFs including measurement of hepatic transaminases(at 2 weeks after initiation of therapy)
- quality of life(at 4, 8, 16 and 24 weeks after initiation of therapy)
- safety profiles of the antifungal agents(at 4, 8, 16 and 24 weeks after initiation of therapy)
- number of adverse events recording(at 2 weeks after initiation of therapy)
- number of courses of steroids and antibiotics recording(at 2 weeks after initiation of therapy)
- laboratory test indicators(at 4, 8, 16 and 24 weeks after initiation of therapy)
- mycological failures(after 1 month)