Q&A: Trial to investigate PAH monotherapy vs. dual therapy in pediatric patients

Key takeaways:

• The Kids MoD PAH Trial is recruiting pediatric patients with newly diagnosed PAH.
• Sildenafil plus bosentan vs. sildenafil only will be evaluated.
• Endpoints are WHO functional class and time to clinical worsening.

There has been little research on optimal treatments for pediatric patients with pulmonary arterial hypertension, but the Kids MoD PAH Trial is expected to change this by clearing up if sildenafil plus bosentan or sildenafil only is better.

According to the study’s webpage on ClinicalTrials.gov, researchers will assess patients aged 3 months to 18 years with World Symposium on Pulmonary Hypertension Groups 1 and 3 PAH in this randomized, open-label, pragmatic phase 3 trial to determine which treatment group (combination therapy vs. monotherapy) has more improvement in WHO functional class from baseline to month 12 and a longer time to clinical worsening at the 24-month mark.

The trial is currently recruiting patients, all of whom must be treatment naïve to participate, according to the webpage.

To learn more about differences in PAH in adult vs. pediatric populations, the Kids MoD PAH Trial and the expected impact of the study, Healio spoke with Lew Romer, MD, professor of anesthesiology and critical care medicine at Johns Hopkins Medicine in Baltimore.

Healio: Are there signs/symptoms of PAH that differ in adults and pediatric patients? How is PAH diagnosis different in these two populations?

Romer: The clinical presentations of pulmonary hypertension (PH) may vary widely and include fatigue, poor exercise tolerance and syncope. Children may also present with failing to thrive or grow properly and decreased performance in other areas of daily life.

Cardiac catheterization remains a major feature of the diagnostic approach for PH in kids and adults, but echocardiography alone may be used for infants aged younger than 1 year in some cases.

Healio: Why have pediatric patients with PAH been overlooked in studies evaluating PAH treatment options?

Romer: There are several reasons for this. Infants, children and adolescents represent a relatively smaller percentage of the overall population that is challenged by PH. Additionally, there is some reluctance to trial new drugs and therapeutic regimens in children that may have challenging side effects.

Healio: Why is it important to find the right treatment modalities for pediatric patients with PAH?

Romer: The burden of morbidity and mortality of pediatric PH is not acceptable at the present time. It is important that we in the field focus on optimizing quality of life and longevity for our patients.

Healio: How could using the treatment modalities that are based on studies in adults potentially harm pediatric patients?

Romer: Drug therapies for PH may affect the liver, systemic blood pressure and other broad-impact circulation issues in the body. These effects may be different and potentially more profound in kids with rapidly growing and changing cardiovascular systems. These drugs are also expensive.

Healio: What reasoning was behind your decision to investigate sildenafil (Viagra) vs. a combination of sildenafil and bosentan in this patient population?

Romer: Studies in adults with PH indicate that combinations of therapies with different mechanisms of action are more effective than single drugs. However, it is still not known if this is true for children or for people of any age with PH due to lung disease — termed by the World Symposium on Pulmonary Hypertension to be “Group 3 PH.”

If combination therapy is best for kids and for people with lung disease-associated PH, then it should be started as early as possible after initial diagnosis. If combination therapy is not the best way forward, then single drugs should be used in order to provide care that has fewer potential toxicities and is more cost-effective care.

Healio: What do you hope to discover in the Kids MoD PAH Trial?

Romer: We hope to determine the best initial treatment for kids with newly diagnosed PAH.

Healio: What impact will your study have on clinicians and patients?

Romer: Our hope is that the data from Kids MoD PAH will inform the pediatric PAH community’s choice of initial therapy for children with PAH. We also hope to provide information about possible clinical trajectories of disease with and without lung disease, and about novel metrics for measuring functional progress of children with PAH.

For more information:

Lew Romer, MD, can be reached at lromer@jhmi.edu.

References:

• Collaco JM, et al. Pulm Circ. 2023;doi:10.1002/pul2.12305.
• Mono vs. dual therapy for pediatric pulmonary arterial hypertension (MoD). https://clinicaltrials.gov/study/NCT04039464. Updated Oct. 15, 2024. Accessed Dec. 5, 2024.