Mono vs. Dual Therapy for Pediatric Pulmonary Arterial Hypertension

• Status: Not yet recruiting
• Trial end date: 2026-09-30
• Target enrollment: 0
• Participant gender: All

Summary

The investigators' central hypothesis is that early combination therapy with two PAH-specific oral therapies that have been shown to be well tolerated in the pediatric population, sildenafil and bosentan, will result in better World Health Organization (WHO) functional class at 12 months after initiation of PAH treatment than therapy with sildenafil alone.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Johns Hopkins University
• Treatments: Bosentan; Sildenafil Citrate

Criteria

Inclusion Criteria:

• Diagnoses of precapillary pulmonary hypertension (PAH) by cardiac catheterization within the previous 4 weeks prior to screening as defined by: mean pulmonary artery pressure > 25 mmHg and/or pulmonary vascular resistance index (PVRI) > 3 Wood units*m2; and pulmonary capillary wedge pressure (or left ventricular end diastolic pressure) < or = 15 mmHg (to rule out significant contributions of left heart disease that may complicate the course and response to therapy);

• Age > or = 4 months to < 18 years;

• Subjects should also meet the following 2 criteria:

• World Symposium on Pulmonary Hypertension Groups 1 or 3;

• Current WHO Functional Classes II or III.

Exclusion Criteria, An individual who meets any of the following criteria will be excluded from participation in this study:

• Inability to obtain informed consent;

• WHO Functional Class IV, or the presence of overt right heart failure (RV) failure with syncope, cyanotic spells or systemic hypotension;

• Evidence of diffuse or focal pulmonary venous disease, left-sided heart functional disease;

• Unrepaired congenital heart disease other than a patent foramen ovale, single ventricles, or Eisenmenger's syndrome;

• Pre-existing standing PAH therapy (calcium channel blockade, phosphodiesterase type 5 inhibitor, endothelin receptor antagonists, or chronic prostanoid). This does not need to include agents used for vasoreactivity testing, or for acute or periprocedural stabilization. All prior PAH therapy must be discontinued for a minimum of seven days prior to enrollment into this study. Safety concerns regarding the prospect of a hiatus in therapy for a wash out period prior to enrollment in this study will be brought to the attention of the DSMB for adjudication;

• History of discontinuation of endothelin receptor antagonists (ERA) or phosphodiesterase-5 inhibitors (PDE5i) treatment due intolerance or safety issues;

• Known hypersensitivity to investigational products, metabolites, or formulation excipients;

• Pregnancy or breastfeeding;

• Documented history in the medical record of noncompliance with previous medical regimens within one year of screening;

• Recent (within 1 year) history of alcohol or illicit drug abuse;

• Participation in a clinical study involving another investigational drug or device within 4 weeks;

• Comorbidities:

• disorders treated with cyclosporine A or glyburide

• disorders treated with cytochrome (CYP3A) Inhibitors and Beta Blockers

• congenital heart disease repaired within 6 months of enrollment;+

• Laboratory values of exclusion:

• serum Alanine Aminotransferase (ALT) or Aspartate Transaminase (AST) lab value that is > bilirubin (2xULN) at the Screening Visit

• serum bilirubin lab value that is > bilirubin (1.5xULN) at the screening visit

• creatinine clearance < 30 mL/min;

• Inability to comply with all study procedures and availability for duration of study;

• age < 4 months or > 18 years (please note that study subjects that are > or = 16 years of age at the time of enrollment will achieve legal majority age by the study's end and a transition to adult status with an adult consent form will be planned for those subjects);

• Inability to take enteral medication;

• Inability to agree to lifestyle considerations throughout the study; For subjects with reproductive potential, those who are unwilling or unable to use an acceptable method of contraception during this protocol and for four weeks thereafter;

• For female participants with reproductive potential, inability to use a highly effective form of contraception for the one month prior to initiation of study drug (note that eligibility may be restored after one month of the use of appropriate contraception).