Revatio Infusions Add No Benefit to Inhaled NO for Newborns With PPHN, Trial Shows

Into the vein (intravenous) injections of Revatio (sildenafil) have no added benefit over inhaled nitric oxide (iNO) used alone in treating newborns with persistent pulmonary hypertension (PPHN), a Phase 3 trial sponsored by Pfizer shows.

Revatio, marketed by Pfizer, was ineffective as an intravenous formulation combined with iNO in reducing treatment failure rates, or time required on iNO treatment, as compared with iNO alone, Pfizer announced in a press release. These results made the trial fail its primary goal.

The study (NCT01720524) was part of an EU Pediatric Investigational Plan, and is taking place at several sites in the U.S., Canada, and Europe.

The trial includes two consecutive parts. Part A was the randomized, placebo-controlled, double-blind phase aiming at addressing the safety and efficacy of intravenous infusions of Revatio, added to inhaled NO.

Newborns, ages 4 days or less, were given infusions at a starting dose of 0.1 mg/kg weight during 30 minutes, followed by a maintenance dose of 0.03 mg/kg per hour. Infusions would last a minimum of 48 hours, and a maximum of 14 days. This was the phase that failed to show superiority of adding Revatio to iNO to treat PPHN.

The trial’s Part B is a long-term follow-up to evaluate developmental progress at 12 and 24 months after the end of the treatment. This part of the trial is still ongoing.

There were two primary efficacy measures — treatment failure rate, and time on iNO treatment. The first was defined by any of three markers: the need for additional PPHN treatment; the need for extracorporeal membrane oxygenation (ECMO), an advanced life-support technique similar to a heart-lung by-pass machine; or death during the study. Time on inhaled NO treatment was measured after initiation of intravenous Revatio.

Results showed the combination of Revatio and iNO therapy failed to be better at either of the two assessed efficacy measures as compared with iNO treatment alone.

In terms of safety, the adverse event profiles of the treatment, and its safety, were consistent with known data for Revatio’s use in pediatric and adult patients with pulmonary arterial hypertension (PAH). Most adverse events were mild to moderate.

Revatio is approved by the U.S. Food and Drug Administration for use in slowing the progression of PAH, and improving individuals’ exercise capacity. The medicine is approved as tablets, intravenous solution, and as an oral suspension. 

In the European Union and Japan, Revatio is approved for treating children with PAH from the age of 1. However, in the U.S., the FDA in August 2012 warned against using Revatio in children.