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

NCT00159913 | Completed Phase 3 Results DMC

• 1 other identifier: A1481131
• Study Type: interventional
• Target: 235
• Locations: 17 countries
• Sites: 41

Brief 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.

Conditions

Pulmonary Arterial Hypertension, Children

Outcome Measures

Primary Outcomes (2)

• Percent Change From Baseline in Peak Volume of Oxygen (VO2) Consumed : Intent To Treat Population

  Peak VO2 (normalized for body weight) at trough plasma levels assessed by CPX testing (bicycle ergometry)at the end of treatment (Week 16 for those who completed the study). Mean Percent change = \[(week 16 value minus baseline mean)/mean at baseline\]\*100%.

  Baseline, Week 16

• Percent Change From Baseline in Peak Volume of Oxygen (VO2) Consumed : Per Protocol Population

  Peak VO2 (normalized for body weight) at trough plasma levels assessed by CPX testing (bicycle ergometry)at the end of treatment (Week 16 for those who completed the study). Mean Percent change = \[(week 16 value minus baseline mean)/mean at baseline\]\*100%.

  Baseline, Week 16

Secondary Outcomes (10)

• Change From Baseline to Week 16 in Mean Pulmonary Artery Pressure (mPAP)

  Baseline, Week 16

• Change From Baseline to Week 16 in Pulmonary Vascular Resistance Index (PVRI)

  Baseline, Week 16

• Percent Change From Baseline to Week 16 in: Respiratory Exchange Ratio (RER)

  Baseline, Week 16

• Percent Change From Baseline to Week 16 in Time to Maximum Volume of Oxygen Consumed (VO2)

  Baseline, Week 16

• Change From Baseline to Week 16 in Pulmonary Vascular Resistance (PVR)

  Baseline, Week 16

Study Arms (4)

Sildenafil Low dose

EXPERIMENTAL

Drug: Sildenafil citrate

Sildenafil Medium dose

EXPERIMENTAL

Drug: Sildenafil citrate

Sildenafil High dose

EXPERIMENTAL

Drug: Sildenafil citrate

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Sildenafil citrate DRUG

oral; 20mg, 40mg and 80 mg; 3 times a day(TID)

Sildenafil High dose

Placebo DRUG

oral; 3 times a day(TID)

Placebo

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Pfizer's Upjohn has merged with Mylan to form Viatris Inc.: lead

Study Sites (41)

Pfizer Investigational Site

Palo Alto, California, 94304, United States

Location

Pfizer Investigational Site

Stanford, California, 94305, United States

Location

Pfizer Investigational Site

Aurora, Colorado, 80045, United States

Location

Pfizer Investigational Site

Boston, Massachusetts, 02115, United States

Location

Pfizer Investigational Site

Ann Arbor, Michigan, 48109, United States

Location

Pfizer Investigational Site

St Louis, Missouri, 63110, United States

Location

Pfizer Investigational Site

New York, New York, 10032, United States

Location

Pfizer Investigational Site

Columbus, Ohio, 43205, United States

Location

Pfizer Investigational Site

Charleston, South Carolina, 29425, United States

Location

Pfizer Investigational Site

Seattle, Washington, 98105, United States

Location

Pfizer Investigational Site

São Paulo, São Paulo, 04012-909, Brazil

Location

Pfizer Investigational Site

Edmonton, Alberta, T6G 2B7, Canada

Location

Pfizer Investigational Site

Santiago, RM, Chile

Location

Pfizer Investigational Site

Medellín, Antioquia, 0, Colombia

Location

Pfizer Investigational Site

Bogota, Cundinamarca, 0, Colombia

Location

Pfizer Investigational Site

Guatemala City, Guatemala

Location

Pfizer Investigational Site

Budapest, 1083, Hungary

Location

Pfizer Investigational Site

Budapest, 1096, Hungary

Location

Pfizer Investigational Site

Deszk, 6722, Hungary

Location

Pfizer Investigational Site

Szeged, 6720, Hungary

Location

Pfizer Investigational Site

Szeged, 6726, Hungary

Location

Pfizer Investigational Site

Hyderabad, Andhra Pradesh, 500 001, India

Location

Pfizer Investigational Site

Kerala, Kochi,, 682 026, India

Location

Pfizer Investigational Site

Bologna, 40138, Italy

Location

Pfizer Investigational Site

Tokyo, Japan

Location

Pfizer Investigational Site

George Town, Pulau Pinang, 10050, Malaysia

Location

Pfizer Investigational Site

George Town, Pulau Pinang, 10900, Malaysia

Location

Pfizer Investigational Site

Del. Tlalpan, Mexico City, 14080, Mexico

Location

Pfizer Investigational Site

Tlalpan, Mexico DF, 14080, Mexico

Location

Pfizer Investigational Site

Lima, L13, Peru

Location

Pfizer Investigational Site

Krakow, 30-663, Poland

Location

Pfizer Investigational Site

Krakow, 31-202, Poland

Location

Pfizer Investigational Site

Warsaw, 04-628, Poland

Location

Pfizer Investigational Site

Warsaw, 04-730, Poland

Location

Pfizer Investigational Site

Zabrze, 41-800, Poland

Location

Pfizer Investigational Site

Moscow, 121552, Russia

Location

Pfizer Investigational Site

Moscow, 127412, Russia

Location

Pfizer Investigational Site

Lund, 221 85, Sweden

Location

Pfizer Investigational Site

Kaohsiung City, 81346, Taiwan

Location

Pfizer Investigational Site

Taipei, 100, Taiwan

Location

Pfizer Investigational Site

Taipei, 11217, Taiwan

Location

Related Publications (5)

• Russell S, Beghetti M, Oudiz R, Balagtas C, Zhang M, Ivy D. Effects of oral sildenafil on exercise capacity in children with pulmonary arterial hypertension: a randomised trial. Open Heart. 2019 Dec 3;6(2):e001149. doi: 10.1136/openhrt-2019-001149. eCollection 2019.

  PMID: 31908813 DERIVED

• Chanu P, Gao X, Bruno R, Claret L, Harnisch L. A modeling and simulation-based assessment of the impact of confounding factors on the readout of a sildenafil survival trial in pulmonary arterial hypertension. J Pharmacokinet Pharmacodyn. 2019 Oct;46(5):499-509. doi: 10.1007/s10928-019-09654-3. Epub 2019 Sep 20.

  PMID: 31538282 DERIVED

• Beghetti M, Rudzinski A, Zhang M. Efficacy and safety of oral sildenafil in children with Down syndrome and pulmonary hypertension. BMC Cardiovasc Disord. 2017 Jul 4;17(1):177. doi: 10.1186/s12872-017-0569-3.

  PMID: 28676038 DERIVED

• Cappelleri JC, Hwang LJ, Mardekian J, Mychaskiw MA. Assessment of measurement properties of peak VO(2) in children with pulmonary arterial hypertension. BMC Pulm Med. 2012 Sep 10;12:54. doi: 10.1186/1471-2466-12-54.

  PMID: 22963001 DERIVED

• Barst RJ, Ivy DD, Gaitan G, Szatmari A, Rudzinski A, Garcia AE, Sastry BK, Pulido T, Layton GR, Serdarevic-Pehar M, Wessel DL. A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial hypertension. Circulation. 2012 Jan 17;125(2):324-34. doi: 10.1161/CIRCULATIONAHA.110.016667. Epub 2011 Nov 29.

  PMID: 22128226 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.govCallCenter@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: September 12, 2005
• Study Start: August 1, 2003
• Primary Completion: June 1, 2008
• Study Completion: June 1, 2008
• Last Updated: February 18, 2021
• Results First Posted: July 21, 2009

Record last verified: 2021-01

Locations

HU (5); US (10); MY (2); PE (1); CO (2); BR (1); TW (3); CA (1); IN (2); SE (1); CL (1); RU (2); GU (1); ME (2); IT (1); JP (1); PL (5)