Clinical trial NCT00159874: A Long Term Extension Study Evaluating Safety Of Sildenafil Citrate When Used To Treat Pulmonary Arterial Hypertension (PAH) In Children
Official title: A Multicenter, Long-Term Extension Study to Assess Safety of Oral Sildenafil Citrate In The Treatment Of Subjects Who Have Completed Study A1481131
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Arterial Hypertension
Keywords: children
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2005-09-12
Enrollment: 234
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Active treatment, dose-blinded extension study evaluating the safety and long term efficacy of sildenafil citrate in children with PAH.


Eligibility criteria: Inclusion Criteria:

* Patients must complete the 16 Week double-blind efficacy study A1481131.

Exclusion Criteria:

* Any patient who did not complete Study A1481131.

Primary outcomes:
measure: Number of Participants Reporting at Least One Adverse Event
timeFrame: Up to Follow-Up visit (30 to 40 days after study completion or treatment discontinuation)
measure: Number of Participants Reporting Treatment-related Adverse Events
timeFrame: Up to Follow-Up visit (30 to 40 days after study completion or treatment discontinuation)
measure: Number of Participants Reporting at Least One Serious Adverse Event
timeFrame: Up to Follow-Up visit (30 to 40 days after study completion or treatment discontinuation)
measure: Number of Participants Reporting Treatment-related Serious Adverse Events
timeFrame: Up to Follow-Up visit (30 to 40 days after study completion or treatment discontinuation)
measure: Number of Deaths Reported in the Study Prior to the Data Monitoring Committee (DMC) Recommendation of Dose Down Titration
timeFrame: Pre-DMC Recommendation dose down titration (04 August 2011)
measure: Number of Deaths Reported During This Study
timeFrame: Last follow-up visit or 30 days after the last administration of study drug
measure: Discontinuation Due to Intolerability
timeFrame: Throughout the treatment duration (median treatment duration 1689 to 1744 days)
measure: Downtitration in Dose Due to Intolerability.
timeFrame: Pre-DMC recomendation (04 August 2011)
measure: Number of Participants With Deterioration Post Baseline in Visual Acuity Safety Tests
timeFrame: Week 36
measure: Number of Participants With Deterioration Post Baseline in Color Vision Monitoring Safety Tests.
timeFrame: Week 36
measure: Pediatric Cognitive Development Status at Week 16.
timeFrame: Week 16
measure: Pediatric Cognitive Development Status at Week 52.
timeFrame: Week 52
measure: Pediatric Motor Development Status at Week 16.
timeFrame: Week 16
measure: Pediatric Motor Development Status at Week 52
timeFrame: Week 52
Secondary outcomes:
measure: Peak Volume of Oxygen (VO2) Consumed at Year 1 Using a Bicycle Ergometry Cardiopulmonary Exercise Test (CPX)
timeFrame: 1 year
measure: Percentage Change From Baseline in Percent Predicted Peak VO2 at Year 1.
timeFrame: Baseline, Year 1
measure: Percent Change From Baseline in Time to Maximum VO2 at Year 1
timeFrame: Baseline, Year 1
measure: Percent Change From Baseline in Respiratory Exchange Ratio at Year 1
timeFrame: Baseline, Year 1
measure: Percent Change From Start of Sildenafil in Total Ventilation (VE) to Year 1
timeFrame: Year 1
measure: Percentage Change From Baseline in End Tidal Oxygen (O2) at Year 1.
timeFrame: Baseline, Year 1
measure: Percentage Change From Baseline in End Tidal Carbon Dioxide (CO2) at Year 1.
timeFrame: Baseline, Year 1
measure: Percentage Change From Baseline in Anaerobic Threshold at Year 1.
timeFrame: Baseline, Year 1
measure: Summary of Shift in Changes From Start of Sildenafil in World Health Organization Pulmonary Hypertension (WHO PH) Functional Class by A1481156 Treatment Group at Year 1.
timeFrame: Baseline, Year 1
measure: Summary of Shift in Changes From Start of Sildenafil in WHO PH Functional Class by A1481156 Treatment Group at Year 2.
timeFrame: Baseline, Year 2
measure: Summary of Shift in Changes From Start of Sildenafil in WHO PH Functional Class by A1481156 Treatment Group at Year 3.
timeFrame: Baseline, Year 3
measure: Summary of Shift in Changes From Start of Sildenafil in WHO PH Functional Class by A1481156 Treatment Group at Year 4.
timeFrame: Baseline, Year 4
measure: Additions From Baseline in Background Therapy up to the End of Study
timeFrame: Up to the end of study
measure: Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF28) as Assessed by the Psychosocial Scale at Year 1.
timeFrame: Baseline, Year 1
measure: Change From Baseline in Child Health Questionnaire-Parent Form (CHQ-PF28) as Assessed by the Physical Scale at Year 1.
timeFrame: Baseline, Year 1
measure: Participant (Parent) Global Assessment at Year 1
timeFrame: Year 1
measure: Physician Global Assessment at Year 1
timeFrame: Year 1
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Pfizer Investigational Site
state: California
city: Palo Alto
country: United States
facility: Pfizer Investigational Site
state: California
city: Stanford
country: United States
facility: Pfizer Investigational Site
state: California
city: Aurora
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Boston
country: United States
facility: Pfizer Investigational Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Pfizer Investigational Site
state: Michigan
city: Saint Louis
country: United States
facility: Pfizer Investigational Site
state: Missouri
city: New York
country: United States
facility: Pfizer Investigational Site
state: New York
city: Columbus
country: United States
facility: Pfizer Investigational Site
state: Ohio
city: Charleston
country: United States
facility: Pfizer Investigational Site
state: South Carolina
city: Seattle
country: United States
facility: Pfizer Investigational Site
state: Washington
city: Sao Paulo
country: Brazil
facility: Pfizer Investigational Site
state: SP
city: São Paulo
country: Brazil
facility: Pfizer Investigational Site
state: SP
city: Puente Alto
country: Chile
facility: Pfizer Investigational Site
state: Santiago
city: Medellin
country: Colombia
facility: Pfizer Investigational Site
state: Antioquia
city: Bogota
country: Colombia
facility: Pfizer Investigational Site
state: Cundinamarca
city: Guatemala
country: Guatemala
facility: Pfizer Investigational Site
city: Budapest
country: Hungary
facility: Pfizer Investigational Site
city: Budapest
country: Hungary
facility: Pfizer Investigational Site
city: Szeged
country: Hungary
facility: Pfizer Investigational Site
city: Hyderabad
country: India
facility: Pfizer Investigational Site
state: Andhra Pradesh
city: Hyderabad
country: India
facility: Pfizer Investigational Site
state: Andhra Pradesh
city: Kochi
country: India
facility: Pfizer Investigational Site
state: Kerala
city: Bologna
country: Italy
facility: Pfizer Investigational Site
city: Tokyo
country: Japan
facility: Pfizer Investigational Site
city: Penang
country: Malaysia
facility: Pfizer Investigational Site
city: Penang
country: Malaysia
facility: Pfizer Investigational Site
city: Penang
country: Malaysia
facility: Pfizer Investigational Site
city: Mexico
country: Mexico
facility: Pfizer Investigational Site
state: DF
city: Krakow
country: Poland
facility: Pfizer Investigational Site
city: Ruda Slaska
country: Poland
facility: Pfizer Investigational Site
city: Warszawa
country: Poland
facility: Pfizer Investigational Site
city: Zabrze
country: Poland
facility: Pfizer Investigational Site
city: Moscow
country: Russian Federation
facility: Pfizer Investigational Site
city: Moscow
country: Russian Federation
facility: Pfizer Investigational Site
city: Lund
country: Sweden
facility: Pfizer Investigational Site
city: Kaohsiung
country: Taiwan
facility: Pfizer Investigational Site
city: Taipei
country: Taiwan
facility: Pfizer Investigational Site
city: Taipei
country: Taiwan
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: Barst RJ, Beghetti M, Pulido T, Layton G, Konourina I, Zhang M, Ivy DD; STARTS-2 Investigators. STARTS-2: long-term survival with oral sildenafil monotherapy in treatment-naive pediatric pulmonary arterial hypertension. Circulation. 2014 May 13;129(19):1914-23. doi: 10.1161/CIRCULATIONAHA.113.005698. Epub 2014 Mar 17.