A Randomized, Double-Blind, Placebo-Controlled Study of Sildenafil in Children With Pulmonary Arterial Hypertension.

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00159913
• Date of registration: 08/09/2005
• Prospective Registration: No
• Primary sponsor: Pfizer
• Public title: A Randomized, Double-Blind, Placebo-Controlled Study of Sildenafil in Children With Pulmonary Arterial Hypertension.
• Scientific title: A Randomized, Double-Blind, Placebo Controlled, Dose Ranging, Parallel Group Study of Oral Sildenafil in the Treatment of Children, Aged 1-17 Years, With Pulmonary Arterial Hypertension.
• Date of first enrolment: August 2003
• Target sample size: 235
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00159913
• Study type: Interventional
• Phase: Phase 3

Countries of recruitment

Australia, Brazil, Canada, Chile, Colombia, Costa Rica, Guatemala, Hungary, India, Italy, Japan, Malaysia, Mexico, Panama, Peru, Poland, Russian Federation, Singapore, Sweden, Taiwan, United States

Contacts

• Name: Pfizer CT.gov Call Center
• Affiliation: Pfizer

Key inclusion & exclusion 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 <= 15 mmHg, and PVRI >= 3 Wood
units x m2 (if PCWP is not available, then mean LA pressure <= 15 mmHg or LVEDP <= 15
mmHg in the absence of left atrial obstruction).

- Females of child bearing potential who were sexually active must have been practicing
a suitable method of birth control so that in the opinion of the investigator, they
would not become pregnant during the study.

- Subjects who have symptomatic pulmonary arterial hypertension due to: primary
pulmonary hypertension; pulmonary arterial hypertension in the presence of a small or
hemodynamically insignificant congenital systemic to pulmonary shunt lesion that in
the opinion of the investigator is not the cause of pulmonary hypertension; collagen
vascular disease; congenital systemic-to-pulmonary shunts with a baseline resting room
air oxygen saturation >= 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 <= 28
mL/kg/min during screening CPX test;

- Written informed consent and assent where applicable before the subject is screened
for the study.

- Subjects who undergo a large shift in altitude (defined as approximately 5000 feet or
1524 meters) in order to participate in the study must reside at the "in study"
altitude for at least 90 days prior to baseline and during the study period.

Exclusion Criteria:

- Subjects with pulmonary hypertension secondary to sickle cell disease, any other
disease known to be associated with PAH, or any etiology other than those specified in
the inclusion criteria.

- Left-sided heart disease, including aortic or mitral valve disease (greater than
mild), restrictive or congestive cardiomyopathy; PCWP or LVEDP > 15 mmHg; LVEF < 40%
determined by MUGA, angiography or echocardiography; LV shortening fraction < 22%
determined by echocardiography, symptomatic coronary disease (demonstrable ischemia).

- Pericardial constriction; significant (2+ for regurgitation) valvular disease other
than tricuspid or pulmonary regurgitation; acutely decompensated heart failure within
previous 30 days from screening; atrial septostomy within previous 6 months of
screening;

- Hemodynamic instability or hypo- or hypertension at screening, i.e., SBP outside of
70-140 mmHg.

- A history of stroke, myocardial infarction or life threatening arrhythmia within 6
months of screening.

- Moderate to severe restrictive pulmonary disease (Total Lung Capacity or Forced Vital
Capacity <= 60% of normal) or history of severe lung disease.

- Subjects with bronchopulmonary dysplasia (BPD) and other chronic lung diseases.

- History of pulmonary embolism.

- Subjects whose CPX test is limited by conditions other than pulmonary
hypertension-associated dyspnea or fatigue.

- Subjects who are known to be HIV positive

- Subjects with impairment of renal function (serum creatinine > 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 < 10 g/dL, leukopenia, WBC < 2500/mL).

- Subjects who previously received bosentan and whose liver function tests taken at
screening are > 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).



Age minimum: 1 Year
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension, Children

Intervention(s)

Drug: Sildenafil citrate

Drug: Placebo

Primary Outcome(s)

Percent Change From Baseline in Peak Volume of Oxygen (VO2) Consumed : Intent To Treat Population [Time Frame: Baseline, Week 16]

Percent Change From Baseline in Peak Volume of Oxygen (VO2) Consumed : Per Protocol Population [Time Frame: Baseline, Week 16]

Secondary Outcome(s)

Change From Baseline to Week 16 in Pulmonary Vascular Resistance Index (PVRI) [Time Frame: Baseline, Week 16]

Change From Baseline to Week 16 in World Health Organization (WHO) Pulmonary Hypertension (PH) Functional Class [Time Frame: Baseline, Week 16]

Change From Baseline to Week 16 in Child Health Questionnaire Parent Form (CHQ-PF28), Physical Scale [Time Frame: Baseline, Week 16]

Change From Baseline to Week 16 in Pulmonary Vascular Resistance (PVR) [Time Frame: Baseline, Week 16]

Percent Change From Baseline to Week 16 in: Respiratory Exchange Ratio (RER) [Time Frame: Baseline, Week 16]

Change From Baseline to Week 16 in Cardiac Index (CI) [Time Frame: Baseline, Week 16]

Change From Baseline to Week 16 in Mean Pulmonary Artery Pressure (mPAP) [Time Frame: Baseline, Week 16]

Change From Baseline to Week 16 in Right Atrial Pressure (RAP) [Time Frame: Baseline, Week 16]

Percent Change From Baseline to Week 16 in Time to Maximum Volume of Oxygen Consumed (VO2) [Time Frame: Baseline, Week 16]

Change From Baseline to Week 16 in Child Health Questionnaire Parent Form (CHQ-PF28), Psychosocial Scales [Time Frame: Baseline, Week 16]

Secondary ID(s)

A1481131

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 21/07/2009
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00159913