Antenatal Sildenafil To Prevent Pulmonary hypertension in congenital diaphragmatic Hernia (SToP-PH): moving from bench to clinical practice

Congenital diaphragmatic hernia (CDH) is a rare disease associated with high mortality and morbidity. Pulmonary hypertension (PHT) is a leading cause of death and morbidity, yet there is no effective post-natal therapy today. A different strategy may be to prevent PHT by antenatal therapy. We and others have shown in two relevant animal models that maternal (transplacental) administration of sildenafil prevents the vascular changes leading to PHT. This prompted us to submit an application for orphan designation for sildenafil in CDH with Avivia as industrial partner. This project will close the gap between our animal experiments and an eventual clinical efficacy trial. We will perform ex-vivo transplacental transfer studies on human placentas to define the clinical dose to use in two short term phase I clinical studies in selected patients. This information will be used to design a phase III multinational randomized placebo-controlled clinical trial to assess efficacy of antenatal sildenafil in fetuses with CDH.

Keywords:hypertension

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences