Miltefosine in Pediatric Cutaneous Leishmaniasis

米替福辛治疗小儿皮肤利什曼病

• 批准号: 7430420
• 负责人: Lyda Elena Osorio
• 金额: $ 22.15万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7430420
• 关键词: Address; Adolescent; Adult; Adverse event; Affect; Age; Age-Years; Amphotericin B; Antimony; Area; Aventis brand of meglumine antimoniate; Behavior; Case Study; Child; Childhood; Cicatrix; Clinical; Clinical Trials; Collaborations; Colombia; Communities; Cutaneous Leishmaniasis; Daily; Data; Databases; Dermal; Doctor of Philosophy; Drug Kinetics; Enrollment; Epidemic; Exposure to; Face; Frequencies; Goals; Group Meetings; Guatemala; Hand; Hospitalization; Household; Immune response; In Vitro; India; Infection; Injection of therapeutic agent; Institution; Investigation; Itraconazole; Ketoconazole; Laboratories; Leishmania; Leishmania viannia; Leishmaniasis; Lesion; Localized; Measures; Metabolic Clearance Rate; Miltefosine; Morbidity - disease rate; Numbers; Oral; Pathogenicity; Patients; Pentamidine; Personal Communication; Pharmaceutical Preparations; Pharmacotherapy; Phlebotominae; Population; Randomized; Relative (related person); Reporting; Research; Research Ethics Committees; Risk; Rural Community; Serum; Specialist; Standards of Weights and Measures; Supervision; Toxic effect; Treatment Failure; Urbanization; Viannia; Visceral Leishmaniasis; Vulnerable Populations; Week; Work; age group; cost; day; disorder prevention; improved; programs; response; transmission process

This multicenter clinical trial will be conducted in Colombia, under the Centra Internacional de Entrenamiento en Investigaciones Medicas (CIDEIM) coordination in collaboration with Lyda Osorio, MD, PhD as Project 1 of the ICIDR program. This study will compare the efficacy and tolerability of the new oral drug, miltefosine with the standard drug therapy, Glucantime in children with cutaneous leishmaniasis (CL) caused by Leishmania of the Viannia subgenus. Pentavalent antimonials have been the standard treatment for CL for more than 50 years in spite of its parenteral use, high toxicity and relative high costs. On the other hand, children constitute a highly vulnerable population since more than 23% of the cases in the major Colombian endemic regions are patients under 12 years of age. Children also have a lower response to antimonial treatment explained by the different pharmacokinetic behaviour in these ages, where approximately half of the exposure to the drug is observed as a result of having twice the clearance rate as compared to adults. These data, along with the different immune response, make children bellow 12 years a population at high risk of treatment failure, increased morbidity, aesthetically deleterious scars or mucosal involvement. 120 children below 12 years will be enrolled. Half of the randomized patients will receive Glucantime 20mg/kg/day for 20 days (standard treatment), and the other half will receive miltefosine 2.5mg/kg/day for 28 days. A 60% efficacy of antimonials and 90% efficacy of miltefosine is expected. Clinical response will be assessed at the end of the treatment, and at 13 and 26 weeks. Also the presence of adverse events will be identified by clinical and laboratory examination. Ethical approval from the Institutional Review Boards at CIDEIM and other participation institutions will be obtained. The availability of an efficacious, tolerable, orally administrable treatment for dermal leishmaniasis would revolutionize the treatment and perhaps even the prevention of this disease.

这项多中心临床试验将在哥伦比亚国际医疗研究中心 (CIDEIM) 的协调下与医学博士 Lyda Osorio 合作，作为 ICIDR 项目的项目 1 在哥伦比亚进行。本研究将比较新型口服药物米替福辛与标准药物治疗葡聚糖时间对由维尼亚亚属利什曼原虫引起的皮肤利什曼病 (CL) 儿童的疗效和耐受性。 50 多年来，五价锑剂一直是 CL 的标准治疗方法，尽管它具有肠外使用、高毒性和相对较高的成本。另一方面，儿童构成了高度脆弱的人群，因为哥伦比亚主要大城市中超过 23% 的病例都是儿童。 流行地区为12岁以下患者。儿童对锑治疗的反应也较低，这是因为这些年龄段的药代动力学行为不同，观察到大约一半的药物暴露是由于其清除率是成人的两倍。这些数据加上不同的免疫反应，使 12 岁以下儿童成为治疗失败、发病率增加、出现不美观的疤痕或粘膜受累的高风险人群。将招收120名12岁以下儿童。一半的随机患者将接受 Glucantime 20mg/kg/天，持续 20 天（标准治疗），另一半患者将接受 Miltefosine 2.5mg/kg/天，持续 28 天。 天。预计锑剂的功效为 60%，米替福辛的功效为 90%。将在治疗结束时以及第 13 周和第 26 周评估临床反应。不良事件的存在也将通过临床和实验室检查来确定。将获得 CIDEIM 机构审查委员会和其他参与机构的道德批准。一种有效的、可耐受的、口服的皮肤利什曼病治疗方法的出现将彻底改变这种疾病的治疗，甚至可能是预防。