Phase 3
N=234
A Randomized, Double-Blind, Placebo-Controlled Study of Sildenafil in Children With Pulmonary Arterial Hypertension.
Pulmonary Arterial Hypertension, Children
Bottom Line
View on ClinicalTrials.gov: NCT00159913 ↗Enrolled (actual)
234
Serious AEs
—
Results posted
Jul 2009
Primary outcome: Primary: Percent Change From Baseline in Peak Volume of Oxygen (VO2) Consumed : Intent To Treat Population — 6.44; 13.40; 10.58; 10.24 percent change — p=0.056
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Sildenafil citrate (Drug); Placebo (Drug)
- Age
- Pediatric · 1+ yrs
- Sex
- All
- Sponsor
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
- Primary completion
- Jun 2008
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Peak Volume of Oxygen (VO2) Consumed : Intent To Treat Population |
6.44; 13.40; 10.58; 10.24; 0.53 | 0.056 |
| PRIMARY Percent Change From Baseline in Peak Volume of Oxygen (VO2) Consumed : Per Protocol Population |
5.43; 15.66; 9.34; 10.10; 2.81 | 0.179 |
| SECONDARY Change From Baseline to Week 16 in Mean Pulmonary Artery Pressure (mPAP) |
0.9; -3.9; -7.4; -4.3; -0.4 | 0.172 |
| SECONDARY Change From Baseline to Week 16 in Pulmonary Vascular Resistance Index (PVRI) |
0.1; -2.9; -5.1; -3.2; 1.6 | 0.041 sig |
| SECONDARY Percent Change From Baseline to Week 16 in: Respiratory Exchange Ratio (RER) |
-0.00; -0.05; -0.02; -0.03; -0.03 | 0.795 |
| SECONDARY Percent Change From Baseline to Week 16 in Time to Maximum Volume of Oxygen Consumed (VO2) |
64.83; 64.42; 31.33; 52.95; 8.84 | 0.139 |
| SECONDARY Change From Baseline to Week 16 in Pulmonary Vascular Resistance (PVR) |
-0.1; -3.3; -5.2; -3.4; 0.1 | 0.172 |
| SECONDARY Change From Baseline to Week 16 in Cardiac Index (CI) |
0.20; 0.02; 0.24; 0.16; -0.60 | 0.015 sig |
| SECONDARY Change From Baseline to Week 16 in Right Atrial Pressure (RAP) |
7.92; 8.05; 7.75; 7.89; 8.11 | 0.440 |
| SECONDARY Change From Baseline to Week 16 in Child Health Questionnaire Parent Form (CHQ-PF28), Physical Scale |
14.0; 9.8; 5.9; 9.4; 8.3 | 0.750 |
| SECONDARY Change From Baseline to Week 16 in Child Health Questionnaire Parent Form (CHQ-PF28), Psychosocial Scales |
5.1; 4.1; 4.3; 4.5; 5.6 | 0.784 |
| SECONDARY Change From Baseline to Week 16 in World Health Organization (WHO) Pulmonary Hypertension (PH) Functional Class |
25; 24; 38; 84; 31; 6 | 0.184 |
Summary
This is a clinical research study designed to evaluate sildenafil for the treatment of Pulmonary Arterial Hypertension in children, aged 1 to 17 years. The purpose of the study is to assess the efficacy, safety, and pharmacokinetics of 16 weeks of chronic treatment with oral sildenafil given in three different doses, compared to placebo (inactive treatment). Efficacy will be measured by exercise and hemodynamics. Patients who complete this trial may be eligible to take part in an extension study, in which all patients will receive active treatment of sildenafil.
Eligibility Criteria
Inclusion Criteria
- Male or female subjects aged from 1 to 17 years old and weighing >= 8 kg with a mean pulmonary artery pressure >= 25 mmHg at rest, PCWP = 3 Wood units x m2 (if PCWP is not available, then mean LA pressure = 88% unrepaired or repaired at least 6 months prior to screening; d-transposition of the great arteries repaired within the first 30 days of life; or surgical repair of other congenital heart lesions at least 6 months prior to screening and do not have clinically significant residual left-sided heart disease consistent with the exclusion criteria.
- Subjects, developmentally able to exercise, whose CPX exercise test functional capacity is within the following parameters: Peak VO2 >= 10 mL/kg/min and 15 mmHg; LVEF 2.5x ULN ) or hepatic function (ALT and/or AST > 3x ULN; and/or bilirubin >= 2 mg/dL). Hematological abnormalities (e.g., severe anemia, Hgb 2x ULN.
- Subjects with any medical condition which in the opinion of the investigator may interfere with treatment, evaluation of safety, and/or efficacy.
- Change in class of medication for CHF or PAH within the 10 days prior to qualifying right heart catheterization.
- Subjects who are currently prescribed and/or taking nitrates or nitric oxide donors in any form. Acute vasodilator testing with nitric oxide is permitted during hemodynamic evaluation; taking chronic arginine supplementation including Heart Bar; therapy involving parenteral inotropic medication or parenteral vasodilators within 3 months of screening; current therapy with alpha-blockers, potent cytochrome P450 3A4 inhibitors (e.g., erythromycin, ketoconazole, itraconazole and protease inhibitors), Ritonavir or Nicorandil; chronic treatment with off-label sildenafil, an endothelin antagonist or prostacyclin/prostacyclin analogue within 30 days of randomization.
- Pregnant or lactating female.
- Any medical or psychological condition or social circumstances that would impair their ability to participate reliably in the study or who were not likely to complete the study for any reason; current or past illicit drug use or alcoholism excepting if abstinence can be documented for >= 1 year.
- Participation in another clinical trial of an investigational drug or device (including placebo) within 30 days of screening for entry into the present study.
- Subjects with known hereditary degenerative retinal disorders (such as retinitis pigmentosa) or history of non-arteritic anterior ischemic optic neuropathy (NAION).
Data sourced from ClinicalTrials.gov (NCT00159913). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.