Randomised multicentre clinical trial to evaluate voriconazole pre-emptive genotyping strategy in patients with risk of aspergillosis: vorigenipharm study protocol.
Randomised multicentre clinical trial to evaluate voriconazole pre-emptive genotyping strategy in patients with risk of aspergillosis: vorigenipharm study protocol.
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DOI：
10.1136/bmjopen-2020-037443
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发表时间：
2020-10-01
期刊：
影响因子：
2.9
通讯作者：
Borobia AM
中科院分区：
文献类型：
--
作者：
Monserrat Villatoro J;García García I;Bueno D;de la Cámara R;Estébanez M;López de la Guía A;Abad-Santos F;Antón C;Mejía G;Otero MJ;Ramírez García E;Frías Iniesta J;Carcas A;Borobia AM
侵袭性曲霉病是血液病患者发病和死亡的最重要原因。伏立康唑是目前治疗侵袭性真菌病的一线药物。伏立康唑的药代动力学个体间变异性取决于遗传因素。CYP 450参与伏立康唑总代谢的70%-75%，主要是CYP 3A 4和CYP 2C 19，其余25%-30%的代谢由单加氧酶黄素进行。CYP 2C 19单核苷酸多态性可以解释伏立康唑代谢变异的50%-55%。主要目的是比较效率的先发制人伏立康唑基因分型与常规做法。主要结局是第5天伏立康唑血清浓度在治疗范围内。次要结局是首次给药后90天内与伏立康唑相关的治疗失败和不良事件的联合变量。共招募146例可能接受伏立康唑治疗的侵袭性曲霉病风险患者，并对CYP 2C 19进行基因分型。如果患者最终接受伏立康唑治疗，将对其进行随机化（1：1实验/对照）。在实验组中，患者将根据药物遗传学算法接受剂量，包括CYP 2C 19基因型以及临床和人口统计学信息。在对照组中，患者将根据临床实践指南接受剂量。此外，还将进行西班牙国家医疗保健系统（NHS）的成本效益评价。将进行每组的直接成本计算。本试验将提供有关在西班牙NHS中实施先发制人的伏立康唑基因分型策略的可行性和成本效益的信息。该方案的西班牙语版本已由拉巴斯大学医院伦理委员会和西班牙药品和医疗器械管理局评估并批准。将提交试验结果，以便在开放的同行评审医学专业特定出版物中发表。Eudra-CT：2019-000376-41和NCT 04238884;预结果。
Invasive aspergillosis is the most important cause of morbidity and mortality in patients with haematological diseases. At present, voriconazole is the first-line treatment for invasive fungal disease. The pharmacokinetic interindividual variability of voriconazole depends on genetic factors. CYP450 is involved in 70%–75% of total metabolism of voriconazole, mainly CYP3A4 and CYP2C19, with the remaining 25%–30% of metabolism conducted by monooxygenase flavins. CYP2C19 single nucleotide polymorphisms could explain 50%–55% of variability in voriconazole metabolism. The main objective is to compare efficiency of pre-emptive voriconazole genotyping with routine practice. The primary outcome is serum voriconazole on the fifth day within the therapeutic range. The secondary outcome is the combined variables of therapeutic failure and adverse events within 90 days of first administration, associated with voriconazole. A total of 146 patients at risk of invasive aspergillosis who will potentially receive voriconazole will be recruited, and CYP2C19 will be genotyped. If the patient ultimately receives voriconazole, they will be randomised (1:1 experimental/control). In the experimental arm, patients will receive a dose according to a pharmacogenetic algorithm, including CYP2C19 genotype and clinical and demographic information. In the control arm, patients will receive a dose according to clinical practice guidelines. In addition, a Spanish National Healthcare System (NHS) point-of-view cost-effectiveness evaluation will be performed. Direct cost calculations for each arm will be performed. This trial will provide information about the viability and cost-effectiveness of the implementation of a pre-emptive voriconazole genotyping strategy in the Spanish NHS. A Spanish version of this protocol has been evaluated and approved by the La Paz University Hospital Ethics Committee and the Spanish Agency of Medicines and Medical Devices. Trial results will be submitted for publication in an open peer-reviewed medical speciality-specific publication. Eudra-CT: 2019-000376-41 and NCT04238884; Pre-results.
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影响因子：
6.7
作者：
通讯作者：
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影响因子：
6.7
作者：
通讯作者：
--
影响因子：
2.1
作者：
Hicks, J. Kevin;Crews, Kristine R.;Relling, Mary V.
通讯作者：
Relling, Mary V.
影响因子：
6.7
作者：
Moriyama B;Obeng AO;Barbarino J;Penzak SR;Henning SA;Scott SA;Agúndez J;Wingard JR;McLeod HL;Klein TE;Cross SJ;Caudle KE;Walsh TJ
通讯作者：
Walsh TJ
DOI：
10.1016/j.eimc.2011.01.010
发表时间：
2011-06-01
影响因子：
2.5
作者：
Fortun, Jesus;Carratala, Jordi;Cuenca-Estrella, Manuel
通讯作者：
Cuenca-Estrella, Manuel