Investigating mono vs dual therapy for pediatric pulmonary arterial hypertension

Lewis Romer, MD, professor of Anesthesiology and Critical Care Medicine at Johns Hopkins University, is the principal investigator of the Mono vs. Dual Therapy for Pediatric Pulmonary Arterial Hypertension (MoD PAH) trial. This Phase 3 study aims to determine the optimal first-line treatment for children newly diagnosed with pulmonary arterial hypertension (PAH).

The trial is currently in the recruiting stage and seeks to enroll pediatric patients to examine the comparative safety and efficacy of sildenafil monotherapy versus sildenafil and bosentan combination therapy.

"Our study is focused on what is the best initial therapy for children with a new diagnosis of pulmonary hypertension," said Romer. "We are trying to address what would seem to be a very fundamental question but one that really is very pressing."

Romer acknowledged the challenges of conducting pediatric clinical trials, particularly in rare diseases like PAH.

"One of the biggest challenges to doing clinical trials for drug therapy in children is the pace of enrollment," he explained. "This is a rare disease. People are very protective of their kids, [questioning] 'What's this business of doing research on my child?' So the pace of enrollment is challenging."

Participants must meet specific inclusion criteria, including a confirmed PAH diagnosis via cardiac catheterization (for children over 1 year old) or 2 echocardiograms (for those under 1 year). Additionally, eligible children must have World Health Organization functional class II or III PAH symptoms.

"We are very interested in quality of life," Romer stated. "We focused on the primary outcome being something called the World Health Organization functional class, which means, do we have symptoms?"

While combination therapy is supported in adult populations, evidence for its use in children remains limited. "There are data to support the use of multiple drugs for initial therapy in adults, but this is a question that has never been asked in children," Romer noted.

Furthermore, the trial includes children with group 1 and group 3 PAH, the latter of which has not been studied in terms of optimal treatment at any age. "We feel that our study represents a great setting to decide that question," said Romer.

The MoD PAH trial represents a critical step toward improving outcomes for children with PAH. Recruitment efforts aim to provide essential evidence for guiding future treatment protocols.

Reference:

Mono vs. Dual Therapy for Pediatric Pulmonary Arterial Hypertension (MoD). ClinicalTrials.gov. Updated October 15, 2024. Accessed Jan. 13, 2025. https://clinicaltrials.gov/study/NCT04039464#contacts-and-locations