Phase 2 Study of Sildenafil for the Treatment of Lymphatic Malformations

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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.