NCT01409031

Study of Sildenafil to Treat Newborns With Persistent Pulmonary Hypertension

Phase II Trial of Sildenafil in Newborns With Persistent Pulmonary Hypertension

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: University of Colorado, Denver · Academic / Other
• Sex: All
• Age: 72 Hours
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine whether intravenous sildenafil reduces pulmonary artery pressure and improves oxygenation in near-term and term infants with persistent pulmonary hypertension.

Detailed description

Term infants with respiratory failure and persistent pulmonary hypertension (PPHN) are among the most critically ill infants in the NICU, with significant mortality and morbidity reported even for infants with moderate disease. Currently, management is largely supportive, and includes oxygen, mechanical ventilation (conventional or high frequency ventilation), and exogenous surfactant therapy. Inhaled nitric oxide (iNO) is a pulmonary vasodilator that was approved for the treatment of hypoxic respiratory failure (HRF) and PPHN of the newborn in 1999 based on clinical trials showing a reduction in the need for rescue treatment with extracorporeal membrane oxygenation (ECMO). One promising therapy to decrease pulmonary arterial pressure and improve oxygenation is sildenafil. Sildenafil is a cGMP-specific phosphodiesterase inhibitor that causes relatively selective pulmonary vasodilation. The use of intravenous (IV) sildenafil was recently FDA approved for use in adults in PPHN. A pilot trial studying dose response and pharmacokinetics in 36 term newborns with PPHN found that IV sildenafil was well tolerated and has the potential to induce marked improvements in oxygenation. The data from this pilot trial provided background to support the dosing regimen for this Phase II trial. We hypothesize that IV sildenafil will acutely reduce pulmonary artery pressure and improve oxygenation in near-term and term infants with PPHN, thus reducing the need for rescue therapy iNO and/or ECMO.

Conditions

• Persistent Pulmonary Hypertension
• Respiratory Failure

Interventions

Type	Name	Description
DRUG	Intravenous Sildenafil	0.4 mg/kg bolus, followed by a continuous infusion of 1.6 mg/kg/day or an equivalent volume of placebo (D5W); infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days.
OTHER	Placebo	An equivalent volume of placebo (D5W)infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days.

Timeline

• Start date: 2011-07-01
• Primary completion: 2013-10-01
• Completion: 2013-10-01
• First posted: 2011-08-03
• Last updated: 2019-02-01
• Results posted: 2019-02-01

Locations

7 sites across 1 country: United States

Regulatory

• FDA-regulated drug study