None listed
Conditions
Interventions
GROUP 1 Type of group
This group will be treated with Sildenafil in a low dose: 10 mg, PO, TID until reaching optimum serum concentrations of 47 ng / ml. The treatment will be administered for 16 weeks.
Group name:GROUP 4 Type of group
This group will be treated with Sildenafil Placebo, PO, TID. Fictitious dose adjustments will be made, if necessary to maintain the blind. Subjects with a weight> 20 kg during the first week will have a low dose of 10 mg, PO, TID and then start with their maximum dose. The treatment will be administered for 16 weeks.
Sponsors
PFIZER S.A.,
Eligibility
Inclusion criteria
Inclusion criteria: 1. Male or female subjects between 1 and 17 years of age. Women of potential age to conceive that they are sexually active should be using an adequate method of birth control. 2. Subjects with a body weight> 8 kilograms. 3. Subjects presenting symptomatic pulmonary arterial hypertension. 4. Subjects with an average pulmonary arterial pressure ≥ 25 mmHg at rest, PCWP ≤ 15 mmHg, and PVRI ≥ 3 units Wood x m2. 5. The subjects, who by their development are trained to perform effort, whose functional capacity in the CPX stress test is within the following parameters: VO2 peak ≥ 10 ml / kg / min and ≤ 28 ml / kg / min during the CPX test at the time of selection. 6. The investigator must obtain the written informed consent and the assent when appropriate, before the subject is reviewed for the study. 7. Subjects who undergo a great change of altitude to participate in the study should remain at the altitude of the place where the study is conducted for at least 90 days before the baseline and during the study period.
Exclusion criteria
Exclusion criteria: 1. Subjects with pulmonary hypertension secondary to sickle cell disease. 2. Left heart disease. 3. Pericardial constriction. 4. Subjects with significant valvular disease other than tricuspid or pulmonary regurgitation; 5. Acute decompensated heart failure in the 30 days prior to selection. 6. Subjects who have undergone an atrial septostomy in the 6 months prior to selection. 7. Subjects with hemodynamic instability or hypo- or hypertension at the time of selection. 8. Subjects with a history of vascular accident, myocardial infarction or arrhythmia that endangers the life of the subject in the 6 months prior to the selection. 9. Subjects with moderate to severe restrictive lung disease or a history of severe lung disease. 10. Subjects with bronchopulmonary dysplasia (BPD) and other chronic pulmonary diseases. 11. Subjects with a history of pulmonary embolism. 12. Subjects whose CPX test is limited by conditions other than dyspnea or fatigue associated with pulmonary hypertension. 13. Subjects with known hereditary degenerative retinal disorders. 14. Subjects that are HIV positive. 15. Subjects with renal insufficiency or hepatic insufficiency. 16. Subjects previously treated with bosentan and whose liver function tests evaluated at the time of selection are> 2 x ULN. 17. Subjects with any medical pathology that may interfere with treatment, assessment of safety, and / or effectiveness. 18. Change in the class of medication to treat congestive heart failure or pulmonary arterial hypertension within 10 days prior to qualifying for right cardiac catheterization. 19. Subjects with current prescription and / or taking nitrates or nitric oxide donors in any form. 20. Subjects who take arginine as a chronic complementary treatment. 21. Subjects who in the 3 months prior to the selection had a treatment consisting of a parenteral inotropic drug or parenteral vasodilators. 22 Subjects treated with alpha blockers or potent cytochrome P450 3A4 inhibitors. 23. Subjects who are receiving Ritonavir or Nicorandil. 24. Subjects who are receiving chronic treatment with generic sildenafil will be excluded. 25. Pregnant or breastfeeding women 26. Subjects that present some medical or psychological pathology or social circumstances that may alter their ability to participate in a reliable manner in the study or that by participating in the study may increase the risk to themselves or to others; 27. Illicit use of drugs or alcohol in the present or in the past. 28. Participation in another clinical study with any medication or device under investigation within 30 days prior to selection. 29. If, in the opinion of the investigator, a subject has no chance of ending the study for any reason.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Cardiopulmonary exercise test (CPX): This is an exercise ergometry test, where the peak volume of oxygen (VO2) consumed is evaluated. Measure:Percentage change in peak VO2 from baseline to the end of treatment. Timepoints:Week 16. | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Criterion 1: The mPAP will be measured by means of a triple lumen thermodilution catheter with balloon tip, using a pressure transducer placed on the axillary line. The patient will be placed in the supine position. The pressure strokes shall be recorded for ≥ 15 seconds. Criterion 2: The PVR will be calculated mathematically based on catheterization data, using average pulmonary arterial pressure, pulmonary capillary wedge pressure and cardiac output. Measure:1) Change in the average pulmonary arterial pressure (mPAP) from baseline until the end of treatment. 2) Change in Pulmonary Vascular Resistance (PVR) from baseline to the end of treatment. Timepoints:Before the treatment and in week 16. ; Outcome name:Criteria 1 and 2: Cardiopulmonary exercise test (CPX) or bicycle ergometry, from which the RER, VO2 data will be extracted Criterion 3, 5: PVRI and RAP is calculated based on the catheterization data with a triple lumen thermodilution catheter with balloon tip + pressure transducer placed in the axillary line. Criterion 4: The IC will be calculated based on parameters extracted from the catheterization (cardiac output and body surface area) Criterion 6: Child Health Questionnaire - Parent Report (CHQ-PF28), is a generic questionnaire validated on the quality of life for subjects 5 years of age or older. Criterion 7: Functional Classification of Pulmonary Hypertension in Accordance with the WHO, is an adaptation of the Criteria of the New York Cardiac Association for Functional and Therapeutic Class, which classifies HP based on its severity of class I to IV. Measure:Percentage change from baseline to the end of treatment: 1) Respiratory exchange rate (RER). 2) Time until reaching VO2 maximum. 3) Pulmonary vascular resistance index (PVRI). 4) Cardiac Index (IC). 5) Right arterial pressure (RAP). 6) Questionnaire on Child Health, Format for parents (CHQ-PF28). 7) HP functional classification. Timepoint | — |
Countries
Australia, Brazil, Canada, Chile, Colombia, Costa Rica, Guatemala, Hungary, India, Italy, Japan, Malasya, Mexico, Panama, Poland, Russian Federation, Singapore, Sweden, Taiwan, United States
Outcome results
None listed