Sildenafil for the Treatment of Lymphatic Malformations

Summary

A Phase 2 study to evaluate safety and efficacy of sildenafil taken orally to improve or resolve lymphatic malformations in children. Subjects may receive either placebo or treatment in an oral dosage with an open label extension for subjects who received placebo. The study treatment assignment will be randomized in a double blind fashion. MRI examination will evaluate change in lesion volume due to treatment. Other safety and efficacy measures will be taken through the 32-week study duration. Funding Source - FDA OOPD

Timeline

Start

2015-05-23

Primary completion

2021-03-30

Completion

2021-03-30

Publications

• Background Abrams D, Schulze-Neick I, Magee AG. Sildenafil as a selective pulmonary vasodilator in childhood primary pulmonary hypertension. Heart. 2000 Aug;84(2):E4. doi: 10.1136/heart.84.2.e4.
• Background Barst RJ, Ivy DD, Gaitan G, Szatmari A, Rudzinski A, Garcia AE, Sastry BK, Pulido T, Layton GR, Serdarevic-Pehar M, Wessel DL. A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial hypertension. Circulation. 2012 Jan 17;125(2):324-34. doi: 10.1161/CIRCULATIONAHA.110.016667. Epub 2011 Nov 29.
• Background Berk DR, Berk EJ, Bruckner AL. A novel method for calculating the volume of hemangiomas. Pediatr Dermatol. 2011 Jul-Aug;28(4):478-82. doi: 10.1111/j.1525-1470.2011.01498.x.
• Background Blei F. Congenital lymphatic malformations. Ann N Y Acad Sci. 2008;1131:185-94. doi: 10.1196/annals.1413.016.
• Background Churchill P, Otal D, Pemberton J, Ali A, Flageole H, Walton JM. Sclerotherapy for lymphatic malformations in children: a scoping review. J Pediatr Surg. 2011 May;46(5):912-22. doi: 10.1016/j.jpedsurg.2011.02.027.
• Background de Graaf M, Breur JMPJ, Raphael MF, Vos M, Breugem CC, Pasmans SGMA. Adverse effects of propranolol when used in the treatment of hemangiomas: a case series of 28 infants. J Am Acad Dermatol. 2011 Aug;65(2):320-327. doi: 10.1016/j.jaad.2010.06.048. Epub 2011 May 20.
• Background Fisher R, Partington A, Dykes E. Cystic hygroma: comparison between prenatal and postnatal diagnosis. J Pediatr Surg. 1996 Apr;31(4):473-6. doi: 10.1016/s0022-3468(96)90477-7.
• Background Frieden IJ, Drolet BA. Propranolol for infantile hemangiomas: promise, peril, pathogenesis. Pediatr Dermatol. 2009 Sep-Oct;26(5):642-4. doi: 10.1111/j.1525-1470.2009.00977.x. No abstract available.
• Background Fuchsmann C, Quintal MC, Giguere C, Ayari-Khalfallah S, Guibaud L, Powell J, McCone C, Froehlich P. Propranolol as first-line treatment of head and neck hemangiomas. Arch Otolaryngol Head Neck Surg. 2011 May;137(5):471-8. doi: 10.1001/archoto.2011.55.
• Background Gallagher PG, Mahoney MJ, Gosche JR. Cystic hygroma in the fetus and newborn. Semin Perinatol. 1999 Aug;23(4):341-56. doi: 10.1016/s0146-0005(99)80042-1.
• Background Greene AK, Perlyn CA, Alomari AI. Management of lymphatic malformations. Clin Plast Surg. 2011 Jan;38(1):75-82. doi: 10.1016/j.cps.2010.08.006.
• Background Howarth ES, Draper ES, Budd JL, Konje JC, Clarke M, Kurinczuk JJ. Population-based study of the outcome following the prenatal diagnosis of cystic hygroma. Prenat Diagn. 2005 Apr;25(4):286-91. doi: 10.1002/pd.1100.
• Background Karatza AA, Bush A, Magee AG. Safety and efficacy of Sildenafil therapy in children with pulmonary hypertension. Int J Cardiol. 2005 Apr 20;100(2):267-73. doi: 10.1016/j.ijcard.2004.09.002.
• Background Leaute-Labreze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taieb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008 Jun 12;358(24):2649-51. doi: 10.1056/NEJMc0708819. No abstract available.
• Background Pfizer. (2007).
• Background Redondo P, Aguado L, Martinez-Cuesta A. Diagnosis and management of extensive vascular malformations of the lower limb: part I. Clinical diagnosis. J Am Acad Dermatol. 2011 Nov;65(5):893-906; quiz 907-8. doi: 10.1016/j.jaad.2010.12.047.
• Background Sans V, de la Roque ED, Berge J, Grenier N, Boralevi F, Mazereeuw-Hautier J, Lipsker D, Dupuis E, Ezzedine K, Vergnes P, Taieb A, Leaute-Labreze C. Propranolol for severe infantile hemangiomas: follow-up report. Pediatrics. 2009 Sep;124(3):e423-31. doi: 10.1542/peds.2008-3458. Epub 2009 Aug 10.
• Background Shekerdemian LS, Ravn HB, Penny DJ. Intravenous sildenafil lowers pulmonary vascular resistance in a model of neonatal pulmonary hypertension. Am J Respir Crit Care Med. 2002 Apr 15;165(8):1098-102. doi: 10.1164/ajrccm.165.8.2107097.
• Background Wang P, Wu P, Egan RW, Billah MM. Identification and characterization of a new human type 9 cGMP-specific phosphodiesterase splice variant (PDE9A5). Differential tissue distribution and subcellular localization of PDE9A variants. Gene. 2003 Sep 18;314:15-27. doi: 10.1016/s0378-1119(03)00733-9.
• Background Whimster IW. The pathology of lymphangioma circumscriptum. Br J Dermatol. 1976 May;94(5):473-86. doi: 10.1111/j.1365-2133.1976.tb05134.x.

Drugs

Indications