Effects of Oral Sildenafil on Mortality in Adults With PAH

Phase 4

Terminated

Conditions: Pulmonary Arterial Hypertension

Interventions: Drug: sildenafil citrate

Registration Number: NCT02060487

Lead Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Brief Summary: This is a blinded study in adult patients with PAH evaluating the relative effects of sildenafil on mortality when administered at the three doses (80 mg, 20 mg or 5 mg, all three times per day \[TID\]). In addition, the relative effects on clinical worsening and 6-minute walking distance (6MWD) will be assessed.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 385

Inclusion Criteria

Subjects ≥ 18 <75 years of age with any of the following conditions:

Idiopathic Primary Pulmonary Arterial Hypertension (IPAH)
PAH secondary to connective tissue disease
PAH with surgical repair (at least 5 years previously) of atrial septal defect (ASD),ventricular septal defect (VSD), patent ductus arteriosus (PDA) and aorto-pulmonary window
PAH diagnosis confirmed by right heart catheterization performed within 12 months prior to randomization
Functional Class II-IV; Baseline 6MWD ≥ 50 m.

Exclusion Criteria

Significant (ie, >2+) valvular disease other than tricuspid regurgitation or pulmonary regurgitation
History of cardiac arrest, respiratory arrest, hemodynamic collapse, CPR, ventricular tachycardia, ventricular fibrillation, or uncontrolled atrial fibrillation
History of pulmonary embolism; History of chronic lung disease / restrictive lung disease (eg, chronic obstructive pulmonary disease (COPD) or scleroderma) with impairment of lung function
No prior long term treatment with PDE-5 inhibitors
Treatment with bosentan OR riociguat within 3 months of randomization
Current treatment with nitrates or nitric oxide

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low dose	sildenafil citrate	-
High dose	sildenafil citrate	-
Medium dose	sildenafil citrate	-

Primary Outcome Measures

Name	Time	Method
Overall Survival	Day 1 of study treatment up to date of death (within a maximum duration of 2102 days)	In this outcome measure number of deaths during the study were reported.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Clinical Worsening Events	Day 1 of study treatment up to date of clinical worsening event (within a maximum duration of 2080 days)	Clinical worsening was defined as all-cause mortality, non-elective hospital stay for worsening pulmonary arterial hypertension (PAH) (including but not limited to right heart failure \[RHF\], initiation of intravenous (IV) prostanoids, lung transplantation, or septostomy) or disease progression. Disease progression was defined as a reduction from baseline in the 6-Minute Walk Distance (6MWD) test by 15% and worsening functional class from baseline, both confirmed by second test within 2 weeks of study treatment.
Change From Baseline in 6-Minute Walk Distance (6MWD) at Month 6	Baseline, Month 6	6MWD was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Analysis was performed using mixed model for repeated measures (MMRM), adjusted for baseline 6MWD and for randomization stratification factors: PAH treatment at study entry and etiology of PAH.
Change From Baseline in 6-Minute Walk Distance (6MWD) at Month 12	Baseline, Month 12	6MWD was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Analysis was performed using mixed model for repeated measures (MMRM), adjusted for baseline 6MWD and for randomization stratification factors: PAH treatment at study entry and etiology of PAH.

Trial Locations

Locations (80): Emory University Investigational Drug Services
🇺🇸
Atlanta, Georgia, United States
The Emory Clinic
🇺🇸
Atlanta, Georgia, United States
Frederik Meijer Heart & Vascular Institute Cardiovascular Research
🇺🇸
Grand Rapids, Michigan, United States
Spectrum Health Butterworth Hospital IDS Pharmacy
🇺🇸
Grand Rapids, Michigan, United States
Spectrum Health Heart & Lung Specialized Care Clinic
🇺🇸
Grand Rapids, Michigan, United States
Spectrum Health Hospitals
🇺🇸
Grand Rapids, Michigan, United States
Spectrum Health Medical Group - Pulmonary Division
🇺🇸
Grand Rapids, Michigan, United States
Spectrum Health
🇺🇸
Grand Rapids, Michigan, United States
Robert V. Sibilia MD, Inc.
🇺🇸
Wooster, Ohio, United States
UT Southwestern Medical School
🇺🇸
Dallas, Texas, United States
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Emory University Investigational Drug Services
🇺🇸Atlanta, Georgia, United States