Pediatric Pulmonary HypertensionPhase 3MoDNCT04039464
Mono vs. Dual Therapy for Pediatric Pulmonary Arterial Hypertension
A Phase 3 study testing Mono-Therapy with Sildenafil and Duo-Therapy with Sildenafil + Bosentan in people with Pediatric Pulmonary Hypertension, run by Johns Hopkins University at 10 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 3 months to 18 years
- Conditions the study is for
- Pediatric Pulmonary Hypertension
- What is being tested?
- Mono-Therapy with Sildenafil and Duo-Therapy with Sildenafil + Bosentan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 10 sitesUnited States
- Study dates
- 1 Aug 2022to 31 Dec 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Children who have not been treated with long-term targeted PAH drug therapy, which include calcium channel blockers (CCB); prostanoids, endothelin receptor antagonists (ERA) or PDE-5 inhibitors (PDE5i) (note that agents used for vasoreactivity testing during cardiac catheterization, or for acute periprocedural stabilization will be discontinued prior to study enrollment these include inhaled nitric oxide and/or prostacyclin analogs) a. Children who have been receiving subtherapeutic dosing of sildenafil (and no other standing therapy) for less than 2 weeks at the time of their referral for evaluation at a PH Center, may be included after a washout period of two days. Subtherapeutic is defined as dosage less than those shown in Section 6.1.2 sildenafil dosing chart. If, prior to the initial diagnostic cardiac catheterization, the independent clinical practitioner is planning to stop low dose sildenafil that is judged to not have therapeutic impact on hemodynamics by echocardiography, one may include this candidate for enrollment. These children will be followed closely during the washout period for clinical findings of cardiorespiratory changes, and with echocardiography and NT-proBNP measurements. Abnormal findings on these screening tests will prompt consideration of acute initiation of inhaled nitric oxide therapy. Therapy for pulmonary hypertension as determined by randomization for the study, may be started immediately after the two day washout period.
- Diagnosis of PAH by cardiology diagnostics
- Diagnosis by cardiac catheterization with in the previous six months: PAH is defined as the presence of mean pulmonary artery pressure > 25mmHg, pulmonary capillary wedge pressure (or left atrial or left ventricular end diastolic pressure) ≤ 15 mmHg, and pulmonary vascular resistance index (PVRI) > 3 Woods Units
- For infants less than one year of age for whom cardiac catheterization is not considered as part of the clinical team's recommended approach, enrollment will be possible without catheterization if the following four criteria are met:
- Two separate echocardiograms clearly demonstrate pulmonary hypertension by at least three of the following metrics:
- Elevated MPA pressure (early diastolic PR peak gradient >20 mmHg)
Show all 15Show fewer
- Right ventricular hypertrophy (qualitative as mild to severe)
- Right atrial enlargement (scales for age will be provided)
- Elevated right ventricular systolic pressure (>35mmHg) on at least two at least two reliable spectral Doppler envelopes during the echocardiogram and in the setting of normal for age documented systolic blood pressure at least two reliable spectral Doppler envelopes during the echocardiogram.
- Flattening or (R to L) bowing of the interventricular septum (qualitative or by elevated eccentricity index)
- Diminished RV function (RV fractional area change <35%) and/or TAPSE below published normal range for age and weight.
- There is no clinical or imaging evidence of left heart dysfunction; iii. Pulmonary venous stenosis and atresia are ruled out by CT angiography or MRI unless all four pulmonary veins are unequivocally normal on the two separate echocardiograms; iv. There is no evidence of hemodynamically significant left-to-right shunting across an unrestricted systemic to pulmonary shunt (this is unlikely to be a concern for PFO, small ASD, or restrictive PDA or VSD).
- Age ≥3 months to < 18 years (until just before the 18th birthday);
- WSPH groups 1 or 3 NOT due to unrepaired congenital heart disease (other than a patent foramen ovale), OR single ventricle, OR Eisenmenger's syndrome (PLEASE NOTE that only patients with Group 1.1, 1.2, 1.3, and 1.4.4 or Group 3 PAH will be included and this does not include those with much rarer presentations with connective tissue disease, HIV infection, portal hypertension, schistosomiasis, or persistent PAH of the newborn);
- Current WHO FC II or III.
Who cannot join
- Inability or failure to provide informed consent;
- The presence of syncope, overt RV failure, cyanotic "spells" or systemic hypotension within 4 weeks of enrollment;
- Evidence of diffuse or focal pulmonary venous disease, left-sided heart functional disease;
- Known hypersensitivity to metabolites, or formulation components such as vehicle, preservatives or fillers that are contained in the investigational drugs;
- Pregnancy or breastfeeding;
- Documented history in the medical record of noncompliance with other medical regimens within one year of screening;
Show all 22Show fewer
- Recent (within 1 year) history of alcohol or illicit drug abuse;
- Participation in any clinical study involving another investigational drug or device within 4 weeks;
- Comorbidities
- Disorders treated with cyclosporine A or glyburide
- Disorders treated with CYP3A Inhibitors and Beta Blockers
- Congenital heart disease that was repaired within 6 months of enrollment;
- A repaired patent ductus arteriosus within two months prior to enrollment does not constitute an exclusion.
- Anatomic issues with a measured Qp:Qs on cardiac catheterization of 1.3 or less are not considered hemodynamically significant and will therefore not be exclusions (i.e. patent foramen ovale, atrial septal defect, small muscular ventricular septal defect, and patent ductus arteriosus)
- Laboratory values of exclusion at the screening visit
- serum ALT or AST lab value that is > 2xULN
- serum bilirubin lab value that is > 1.5xULN
- creatinine clearance < 30 mL/min;
- Inability to comply with all study procedures and availability for duration of study;
- Inability to take oral medications as prescribed;
- Inability to agree to lifestyle considerations throughout the study (please see section 5.3) and for four weeks thereafter.
- Children over 1 year of age with WSPH group 1 PAH attributed to IPAH or HPAH who are robustly responsive to acute vasodilator testing and who might benefit from a first line trial of oral CCB therapy as assessed by the treating physician and as described in PAH guidelines.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
Johns Hopkins Medical Institutions
Baltimore, Maryland, 21287
Boston Children's Hospital
Boston, Massachusetts, 02115
Baylor College of Medicine
Houston, Texas, 77030
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Columbia University Medical Center
New York, New York, 10032
Seattle Children's Hospital
Seattle, Washington, 98105
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
New York Medical College
Valhalla, New York, 10595
About this study
Official title: Kids MoD PAH Trial: Mono- vs. Duo-Therapy for Pediatric Pulmonary Arterial Hypertension
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.
Read the detailed description
A Phase III, randomized, open label, pragmatic trial to compare the safety and efficacy of first-line combination therapy (sildenafil and bosentan) to first-line monotherapy (sildenafil alone) in pediatric subjects with WHO Functional Classes II or III and precapillary pulmonary hypertension of Group 1 (PAH caused by idiopathic, heritable, drugs or toxins, congenital heart disease, or connective tissue disease) or Group 3 (PAH caused by lung disease or hypoxemia) according to the WHO (Nice) classification system. Precapillary pulmonary hypertension will be defined by standard criteria as mean pulmonary artery pressure over 25 mmHg and/or pulmonary vascular resistance index (PVRI) > 3, as well as pulmonary capillary wedge pressure (or left ventricular end diastolic pressure) ≤ 15 mmHg as determined by cardiac catheterization.
For infants less than one year of age for whom cardiac catheterization is not considered as part of the clinical team's recommended approach, enrollment will be possible without catheterization if the following four criteria (i-iv) are met:
- Two separate echocardiograms clearly demonstrate pulmonary hypertension by at least three of the following metrics
- Elevated MPA pressure (early diastolic PR peak gradient >20 mmHg)
- Right ventricular hypertrophy (qualitative as mild to severe)
- Right atrial enlargement (scales for age will be provided)
- Elevated right ventricular systolic pressure (>35mmHg) on at least two at least two reliable spectral Doppler envelopes during the echocardiogram and in the setting of normal for age documented systolic blood pressure at least two reliable spectral Doppler envelopes during the echocardiogram
- Flattening or (R to L) bowing of the interventricular septum (qualitative or by elevated eccentricity index)
- Diminished RV function (RV fractional area change <35%) and/or TAPSE below published normal range for age and weight; ii. There is no clinical or imaging evidence of left heart dysfunction; iii. Pulmonary venous stenosis and atresia are ruled out by CT angiography or MRI unless all four pulmonary veins are unequivocally normal on the two separate echocardiograms; iv. There is no evidence of hemodynamically significant left-to-right shunting across an unrestricted systemic to pulmonary shunt.
Study subjects will be followed with current standard of care assessments and diagnostics, including longitudinal clinical evaluations, determinations of functional class (FC), serial NT-pro-Brain Natriuretic Peptide (NT-proBNP) levels, and echocardiography. Data from these studies will be analyzed in central core facilities that will be used by all participating study sites.
Clinical endpoints are the focus of this study. However, additional data collection is planned for exploratory aims to examine the potential role for future application of novel metrics of outcomes in children with PAH (e.g., pediatric QOL and actigraphy), as described below. The investigators also plan to collect blood, swab and urine samples to determine whether inherent genomic variations or novel proteomic biomarkers will associate with clinical responsiveness to interventions within the cohort. Bio-specimens will be obtained to further test the hypothesis that therapeutic responders will have a different genomic or proteomic profile as compared to subjects who do not respond well to therapy.
Bio-specimens will include the following:
- Blood for DNA, peripheral blood mononuclear cells, plasma, and serum; and
- Paired Box Gene (PAXgene) tubes for RNA and miRNA studies; and
- Urine for biomarker analysis.
Because sildenafil and bosentan have different mechanisms of action targeting different intracellular pathways, combination therapy is a rational treatment strategy for pediatric patients with PAH. Past work in adult PAH suggests that combination therapy with longer duration agents with the same mechanisms of action may cause greater and more sustained improvement in clinical course in comparison with monotherapy. Whether children with PAH respond and tolerate combination therapy better than monotherapy has not been studied. In addition, despite a growing experience with sequential therapy, additional medications are added only after clinical deterioration or failure to sustain responsiveness.
Pharmacokinetics will be assessed during this study in order to determine whether drug levels or compliance with therapy affect outcomes in this cohort. In addition, pharmacokinetics data and related clinical responses from mono- and dual therapy participants will be compared. Interactions between these agents are well known, whereby bosentan decreases sildenafil levels. As a result, sildenafil levels during mono- and combination therapy will be further defined by the planned pharmacokinetics in the current protocol. In addition to strengthening this current study design, such data will form a basis for optimizing the use of these agents and potential strategies for dose adjustments in the broader scope of clinical care in the future.
- Conditions
- Pediatric Pulmonary Hypertension
- Being tested
- Mono-Therapy with Sildenafil, Duo-Therapy with Sildenafil + Bosentan
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mono-Therapy with SildenafilDrug
Also called Revatio monotherapy
The subjects will be randomized to receive sildenafil alone and will undergo study procedures as outlined in section 1.3. There will not be a placebo group.
Duo-Therapy with Sildenafil + BosentanDrug
Also called Dual therapy with Revatio and Tracleer
The subjects will be randomized to receive combination up-front therapy sildenafil and bosentan and will undergo study procedures as outlined in section 1.3. There will not be a placebo group.
| Study group | Role | What they receive |
|---|---|---|
| Monotherapy with Sildenafil Group | Active comparator | mono-therapy: first-line monotherapy (sildenafil alone) - in pediatric subjects with PAH. Receives: Drug: Mono-Therapy with Sildenafil |
| Duo Therapy with Sildenafil + Bosentan Group | Active comparator | duo-therapy: compare two treatment strategies - first-line combination therapy (sildenafil and bosentan) Receives: Drug: Duo-Therapy with Sildenafil + Bosentan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in WHO functional class (FC) of Mono vs. Dual Therapy
There are four WHO functional classes: Class I: Pulmonary hypertension without resulting limitation of physical activity; Ordinary physical activity does not cause undue dyspnea or fatigue, or chest pain or near-syncope; Class II: Pulmonary hypertension resulting in a slight limitation of physical activity; Comfortable at rest; Ordinary physical activity causes undue dyspnea or fatigue, or chest pain or near-syncope; Class III: Pulmonary hypertension resulting in a marked limitation of physical activity; Comfortable at rest; Less than ordinary physical activity causes undue dyspnea or fatigue, or chest pain or near-syncope; Class IV: Pulmonary hypertension resulting in inability to carry out any physical activity without symptoms; Signs of right heart failure; Marked limitation of physical activity; Dyspnea and/or fatigue may be present at rest; Discomfort.
This will be an assessment of a change from one class to another per participant in each arm.
Measured: Baseline, 12 months
Secondary outcomes (1)
Time to clinical worsening (TTCW)
TTCW has become increasingly used in multicenter randomized clinical trials of adult pulmonary hypertension (PH) and will be used in this trial to capture time (in days) from study enrollment to clinical worsening. Disease progression will be defined as deterioration in WHO FC and the need for additional therapy for subjects less than 8 years of age. Subjects that are over 8 years old will follow adult criteria for this event - both deterioration in WHO FC and more than a 15% decrease in 6 minute walk distance (MWD) from baseline. TTCW is defined as a composite including disease progression, hospitalization for worsening PH, addition of other prostanoid drug therapies, Potts shunt, lung transplantation or atrial septostomy, and all-cause death.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2019
- Study start1 Aug 2022
- Primary completion31 Dec 2025
- Study completion31 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pediatric Pulmonary HypertensionStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), National Center for Advancing Translational Sciences (NCATS)
- Responsible party
- Sponsor
- Investigators
- Lewis Romer, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04039464
- Sponsor's protocol ID
- IRB00300590
- Other IDs
- UG3HL151458, UH3HL151458, 1U24TR001609, 1U24TR004440
- Acronym
- MoD
- Status last verified
- Feb 2026
- First submitted
- 1 Jul 2019
- Last updated
- 18 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: This study will be conducted in accordance with the following publication and data sharing policies and regulations: National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the published results of NIH funded research. It requires scientists to submit final peer-reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for publication. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed journals.
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Kids MoD PAH Trial: Mono- vs. Duo-Therapy for Pediatric Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT04039464
- Acronym / sponsor ID
- MoD / IRB00300590
- Conditions
- Pediatric Pulmonary Hypertension
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), National Center for Advancing Translational Sciences (NCATS)
- Study start
- 1 Aug 2022 (actual)
- Primary completion
- 31 Dec 2025 (actual)
- Study completion
- 31 Dec 2025 (actual)
- First posted
- 31 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A Phase III, randomized, open label, pragmatic trial to compare the safety and efficacy of first-line combination therapy (sildenafil and bosentan) to first-line monotherapy (sildenafil alone) in pediatric subjects with WHO Functional Classes II or III and precapillary pulmonary hypertension of Group 1 (PAH caused by idiopathic, heritable, drugs or toxins, congenital heart disease, or connective tissue disease) or Group 3 (PAH caused by lung disease or hypoxemia) according to the WHO (Nice) classification system. Precapillary pulmonary hypertension will be defined by standard criteria as mean pulmonary artery pressure over 25 mmHg and/or pulmonary vascular resistance index (PVRI) > 3, as well as pulmonary capillary wedge pressure (or left ventricular end diastolic pressure) ≤ 15 mmHg as determined by cardiac catheterization.
For infants less than one year of age for whom cardiac catheterization is not considered as part of the clinical team's recommended approach, enrollment will be possible without catheterization if the following four criteria (i-iv) are met:
- Two separate echocardiograms clearly demonstrate pulmonary hypertension by at least three of the following metrics
- Elevated MPA pressure (early diastolic PR peak gradient >20 mmHg)
- Right ventricular hypertrophy (qualitative as mild to severe)
- Right atrial enlargement (scales for age will be provided)
- Elevated right ventricular systolic pressure (>35mmHg) on at least two at least two reliable spectral Doppler envelopes during the echocardiogram and in the setting of normal for age documented systolic blood pressure at least two reliable spectral Doppler envelopes during the echocardiogram
- Flattening or (R to L) bowing of the interventricular septum (qualitative or by elevated eccentricity index)
- Diminished RV function (RV fractional area change <35%) and/or TAPSE below published normal range for age and weight; ii. There is no clinical or imaging evidence of left heart dysfunction; iii. Pulmonary venous stenosis and atresia are ruled out by CT angiography or MRI unless all four pulmonary veins are unequivocally normal on the two separate echocardiograms; iv. There is no evidence of hemodynamically significant left-to-right shunting across an unrestricted systemic to pulmonary shunt.
Study subjects will be followed with current standard of care assessments and diagnostics, including longitudinal clinical evaluations, determinations of functional class (FC), serial NT-pro-Brain Natriuretic Peptide (NT-proBNP) levels, and echocardiography. Data from these studies will be analyzed in central core facilities that will be used by all participating study sites.
Clinical endpoints are the focus of this study. However, additional data collection is planned for exploratory aims to examine the potential role for future application of novel metrics of outcomes in children with PAH (e.g., pediatric QOL and actigraphy), as described below. The investigators also plan to collect blood, swab and urine samples to determine whether inherent genomic variations or novel proteomic biomarkers will associate with clinical responsiveness to interventions within the cohort. Bio-specimens will be obtained to further test the hypothesis that therapeutic responders will have a different genomic or proteomic profile as compared to subjects who do not respond well to therapy.
Bio-specimens will include the following:
- Blood for DNA, peripheral blood mononuclear cells, plasma, and serum; and
- Paired Box Gene (PAXgene) tubes for RNA and miRNA studies; and
- Urine for biomarker analysis.
Because sildenafil and bosentan have different mechanisms of action targeting different intracellular pathways, combination therapy is a rational treatment strategy for pediatric patients with PAH. Past work in adult PAH suggests that combination therapy with longer duration agents with the same mechanisms of action may cause greater and more sustained improvement in clinical course in comparison with monotherapy. Whether children with PAH respond and tolerate combination therapy better than monotherapy has not been studied. In addition, despite a growing experience with sequential therapy, additional medications are added only after clinical deterioration or failure to sustain responsiveness.
Pharmacokinetics will be assessed during this study in order to determine whether drug levels or compliance with therapy affect outcomes in this cohort. In addition, pharmacokinetics data and related clinical responses from mono- and dual therapy participants will be compared. Interactions between these agents are well known, whereby bosentan decreases sildenafil levels. As a result, sildenafil levels during mono- and combination therapy will be further defined by the planned pharmacokinetics in the current protocol. In addition to strengthening this current study design, such data will form a basis for optimizing the use of these agents and potential strategies for dose adjustments in the broader scope of clinical care in the future.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Monotherapy with Sildenafil Group | Active comparator | Drug: Mono-Therapy with Sildenafilmono-therapy: first-line monotherapy (sildenafil alone) - in pediatric subjects with PAH. |
| Duo Therapy with Sildenafil + Bosentan Group | Active comparator | Drug: Duo-Therapy with Sildenafil + Bosentanduo-therapy: compare two treatment strategies - first-line combination therapy (sildenafil and bosentan) |
Who may qualify
- Ages
- 3 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (15 listed)
- Children who have not been treated with long-term targeted PAH drug therapy, which include calcium channel blockers (CCB); prostanoids, endothelin receptor antagonists (ERA) or PDE-5 inhibitors (PDE5i) (note that agents used for vasoreactivity testing during cardiac catheterization, or for acute periprocedural stabilization will be discontinued prior to study enrollment these include inhaled nitric oxide and/or prostacyclin analogs) a. Children who have been receiving subtherapeutic dosing of sildenafil (and no other standing therapy) for less than 2 weeks at the time of their referral for evaluation at a PH Center, may be included after a washout period of two days. Subtherapeutic is defined as dosage less than those shown in Section 6.1.2 sildenafil dosing chart. If, prior to the initial diagnostic cardiac catheterization, the independent clinical practitioner is planning to stop low dose sildenafil that is judged to not have therapeutic impact on hemodynamics by echocardiography, one may include this candidate for enrollment. These children will be followed closely during the washout period for clinical findings of cardiorespiratory changes, and with echocardiography and NT-proBNP measurements. Abnormal findings on these screening tests will prompt consideration of acute initiation of inhaled nitric oxide therapy. Therapy for pulmonary hypertension as determined by randomization for the study, may be started immediately after the two day washout period.
- Diagnosis of PAH by cardiology diagnostics
- There is no clinical or imaging evidence of left heart dysfunction; iii. Pulmonary venous stenosis and atresia are ruled out by CT angiography or MRI unless all four pulmonary veins are unequivocally normal on the two separate echocardiograms; iv. There is no evidence of hemodynamically significant left-to-right shunting across an unrestricted systemic to pulmonary shunt (this is unlikely to be a concern for PFO, small ASD, or restrictive PDA or VSD).
- Age ≥3 months to < 18 years (until just before the 18th birthday);
- WSPH groups 1 or 3 NOT due to unrepaired congenital heart disease (other than a patent foramen ovale), OR single ventricle, OR Eisenmenger's syndrome (PLEASE NOTE that only patients with Group 1.1, 1.2, 1.3, and 1.4.4 or Group 3 PAH will be included and this does not include those with much rarer presentations with connective tissue disease, HIV infection, portal hypertension, schistosomiasis, or persistent PAH of the newborn);
Key exclusion criteria (22 listed)
- Inability or failure to provide informed consent;
- The presence of syncope, overt RV failure, cyanotic "spells" or systemic hypotension within 4 weeks of enrollment;
- Evidence of diffuse or focal pulmonary venous disease, left-sided heart functional disease;
- Known hypersensitivity to metabolites, or formulation components such as vehicle, preservatives or fillers that are contained in the investigational drugs;
- Pregnancy or breastfeeding;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mono-Therapy with SildenafilAlso: Revatio monotherapyThe subjects will be randomized to receive sildenafil alone and will undergo study procedures as outlined in section 1.3. There will not be a placebo group. | Drug | Monotherapy with Sildenafil Group |
| Duo-Therapy with Sildenafil + BosentanAlso: Dual therapy with Revatio and TracleerThe subjects will be randomized to receive combination up-front therapy sildenafil and bosentan and will undergo study procedures as outlined in section 1.3. There will not be a placebo group. | Drug | Duo Therapy with Sildenafil + Bosentan Group |
Primary outcome
Change in WHO functional class (FC) of Mono vs. Dual Therapy
Time frame: Baseline, 12 months
There are four WHO functional classes: Class I: Pulmonary hypertension without resulting limitation of physical activity; Ordinary physical activity does not cause undue dyspnea or fatigue, or chest pain or near-syncope; Class II: Pulmonary hypertension resulting in a slight limitation of physical activity; Comfortable at rest; Ordinary physical activity causes undue dyspnea or fatigue, or chest pain or near-syncope; Class III: Pulmonary hypertension resulting in a marked limitation of physical activity; Comfortable at rest; Less than ordinary physical activity causes undue dyspnea or fatigue, or chest pain or near-syncope; Class IV: Pulmonary hypertension resulting in inability to carry out any physical activity without symptoms; Signs of right heart failure; Marked limitation of physical activity; Dyspnea and/or fatigue may be present at rest; Discomfort. This will be an assessment of a change from one class to another per participant in each arm.
1 secondary outcome
Time to clinical worsening (TTCW)
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2026.
- Individual participant dataSharing planned: Yes. This study will be conducted in accordance with the following publication and data sharing policies and regulations: National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the published results of NIH funded research. It requires scientists to submit final peer-reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for publication. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed journals.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lewis Romer, MD principal investigator
Johns Hopkins University
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Mono-Therapy with Sildenafil and Duo-Therapy with Sildenafil + Bosentan in people with Pediatric Pulmonary Hypertension, run by Johns Hopkins University at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in WHO functional class (FC) of Mono vs. Dual Therapy (time frame: Baseline, 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2026.