Phase 2 Study of Sildenafil for the Treatment of Lymphatic Malformations

描述：（申请人提供） 淋巴管畸形（LM）是局部区域的异常发展， 淋巴系统，通常发生在头部和颈部的儿童。LM被认为是一种罕见或罕见的疾病，其引起的并发症包括疼痛、溃疡、继发性感染、其他器官浸润和死亡。目前的治疗包括手术切除或化学或物理破坏部分病变的方法。没有一种疗法是一致有效的，并且都有发生重大不良事件的风险。申请方报告称，最近一例接受西地那非口服治疗肺动脉高压的儿童LM病变几乎完全消退。本临床研究试验的目的是记录西地那非治疗LM的获益或无获益，并确定哪种类型的患者将 从西地那非中获益。 这项研究是一项双盲安慰剂对照试验，40名年龄在6个月至10岁之间的儿童患有大型（直径至少3 cm）LM，接受基于体重的药物剂量治疗20周。 该试验涉及使用MRI分割技术精确记录与治疗或安慰剂相关的体积变化。 在20周时，活性药物组的患者将停用西地那非12周，而安慰剂组的患者有机会服用活性药物20周。主要终点是通过磁共振成像（MRI）评价的病变体积变化，次要终点是医生和受试者评价。 研究者还将使用临床评价评分和调查观察并记录西地那非或安慰剂的临床应答。研究结果应确定LM病变的特征，这些特征可能提示对西地那非治疗的有益反应。

DESCRIPTION: (provided by the applicant) Lymphatic malformations (LMs) are localized areas of abnormal development of the lymphatic system that commonly occur in the head and neck of children. LMs are considered a rare or orphan disease which causes complications including pain, ulceration, secondary infection, infiltration of other organs, and death. Current therapies involve surgical excision or methods of chemical or physical destruction of portions of lesions. No therapies are uniformly effective and all have the risk of significant adverse events. The applicant reported a recent almost complete resolution of a LM lesion in a child who was treated with sildenafil oral therapy for pulmonary arterial hypertension. The goal of this clinical research trial is to document the benefit or absence of benefit of sildenafil therapy for LMs and identify which type of patient will benefit from sildenafil. This study is a double-blind placebo-controlled trial of 40 children aged 6 months to 10 years with large (at least 3 cm diameter) LMs to be treated for 20 weeks with a weight-based dose of the medication. The trial involves precise documentation of volume changes associated with therapy or placebo by using MRI segmentation techniques. At 20 weeks, those on active drug are to discontinue sildenafil for 12 weeks while those on placebo are offered the opportunity to take the active medication for 20 weeks. The primary endpoint is change in lesion volume as evaluated by magnetic resonance imaging (MRI) with secondary endpoints of physician and subject evaluations. The investigators will also observe and document the clinical response to sildenafil or placebo using clinical evaluation scores and surveys. The results of the study should identify characteristics of LM lesions which may suggest a beneficial response to sildenafil therapy.