S4.5a A randomized, double blind phase II proof-of-concept superiority trial of fosravuconazole 200 mg or 300 mg weekly dose versus itraconazole 400 mg daily, all three arms in combination with surgery, in patients with eumycetoma in Sudan—top line results
S4.5a A randomized, double blind phase II proof-of-concept superiority trial of fosravuconazole 200 mg or 300 mg weekly dose versus itraconazole 400 mg daily, all three arms in combination with surgery, in patients with eumycetoma in Sudan—top line results
复制标题
DOI：
10.1093/mmy/myac072.s4.5a
复制
发表时间：
2022-09-20
期刊：
影响因子：
2.9
通讯作者：
Strub-Wourgaft, Nathalie
中科院分区：
文献类型：
--
作者：
Fahal, Ahmed Hassan;Bakhiet, Sahar Mubarak;Mohamed, El Samani Wadaa;Ahmed, Eiman Siddig;Bakhiet, Osama El Hadi;Yousif, Abu Bakar Ahmed;Fahal, Lamis Ahmed;Alla, Hadel Yassir Atta;Razig, A. Razig Osman A.;Siddig, Emmanuel Edwar;Hassan, Omnia Babekir;Abdulla, Sahar A. Rahman;Mohaemd, Amir Faroug;Jodda, Nagwa Adam;Bahar, Mustafa El Nour;Nyaoke, Borna A.;Egondi, Thaddaeus;Oyieko, Peelen;Zijlstra, Eduard E.;Strub-Wourgaft, Nathalie
确定除手术外，在由马杜拉菌引起的小至中度真菌瘤病变患者中，每周一次200 mg或300 mg的福瑞康唑（Fos）单药治疗[定义为治疗结束（EOT; 52周）访视时完全治愈]是否比伊曲康唑（Itra）单药治疗的标准治疗12个月方案更有效。这是一项在需要手术的真菌瘤受试者中进行的单中心（真菌瘤研究中心，苏丹喀土穆）、比较、随机、双盲、平行组、活性对照、临床优效性试验。参与者以1：1：1的比例随机分配。在第1组中，参与者在第1天、第2天和第3天接受负荷剂量的Fos 300 mg，随后每周一次接受300 mg剂量，共持续12个月。在第2组中，参与者在第1天、第2天和第3天服用Fos 200 mg，随后每周服用200 mg，共持续12个月。在第3组中，参与者每天服用400 mg Itra，持续12个月。所有患者均在治疗6个月后接受手术，切除剩余病变。足菌肿病变直径在2至≤16 cm之间。年龄临界值为≥15岁。M. PCR证实为霉菌病。安全性监测包括重度和严重治疗相关事件。共筛选了122例受试者，入组了104例受试者（Fos 300 mg组34例，Fos 200 mg每周一次组34例，Itra 400 mg组36例）。治疗12个月（EOT）后完全治愈，表现为无足菌肿肿块、鼻窦和分泌物;病变部位超声检查正常或MRI正常;如果存在足菌肿肿块，则手术活检真菌培养阴性。在mITT人群中评估完全治愈率。在符合方案人群中进行次要疗效分析。此外，年龄，临床症状和体征的变化，大小和病变的持续时间对结果的影响进行了检查。安全性令人满意，依从性良好。这是第一个随机对照试验，比较两种唑类药物，fosravuconazole（两种剂量方案）和伊曲康唑，联合手术。详细的疗效和安全性结果将在口头报告中进行交流和讨论。
To determine whether, in addition to surgery, fosravuconazole (Fos) monotherapy of either 200 mg or 300 mg weekly was more effective [defined as complete cure at the End of Treatment (EOT; 52-week) visit] than the standard-of-care 12-month regimen of itraconazole (Itra) monotherapy, in patients with small to moderate eumycetoma lesions caused by Madurella mycetomatis. This was a single-center (Mycetoma Research Center, Khartoum, Sudan), comparative, randomized, double-blind, parallel-group, active-controlled, clinical superiority trial in participants with eumycetoma requiring surgery. Participants were randomized in a 1:1:1 ratio. In Arm 1 participants took a loading dose of Fos 300 mg on Day 1, Day 2, and Day 3, followed by a weekly dose of 300 mg for a total duration of 12 months. In Arm 2 participants took Fos 200 mg on Day 1, Day 2, and Day 3, followed by a weekly dose of 200 mg for a total duration of 12 months. In Arm 3 participants took Itra 400 mg daily for 12 months. All patients underwent surgery after 6 months of treatment in which the remaining lesion was removed. Mycetoma lesions were between 2 to ≤16 cm in diameter. The age cut-off was ≥15 years. The diagnosis of M. mycetomatis was confirmed by PCR. Safety monitoring included, among other, severe, and serious treatment-related events. A total of 122 participants were screened and 104 participants were enrolled (34 in Fos 300 mg, 34 in Fos 200 mg weekly, and 36 in Itra 400 mg). Complete cure after 12 months (EOT) of treatment was demonstrated in terms of an absence of eumycetoma mass, sinuses, and discharge; normal ultrasound of the lesion site or normal MRI; and a negative fungal culture from a surgical biopsy if a mycetoma mass was present. The complete cure rate was assessed in the mITT population. Secondary efficacy analyses were performed in the Per Protocol population. In addition, the influence of age, changes in clinical symptoms and signs, size, and duration of the lesion on outcome was examined. Safety was satisfactory and compliance was good. This is the first randomized controlled trial in eumycetoma, comparing two azoles, fosravuconazole (two dosage regimens) and itraconazole, in combination with surgery. Detailed efficacy and safety results will be communicated and discussed in the oral presentation.