Overview

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).