Study Stopped
Study was terminated by Sponsor at recommendation of Data Monitoring Committee after completion of first interim analysis as primary objective was met.
Effects of Oral Sildenafil on Mortality in Adults With PAH
AFFILIATE
A MULTINATIONAL, MULTICENTER STUDY TO ASSESS THE EFFECTS OF ORAL SILDENAFIL ON MORTALITY IN ADULTS WITH PULMONARY ARTERIAL HYPERTENSION (PAH)
3 other identifiers
interventional
385
23 countries
82
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Sep 2014
Longer than P75 for phase_4
82 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 29, 2014
CompletedFirst Posted
Study publicly available on registry
February 12, 2014
CompletedStudy Start
First participant enrolled
September 22, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 26, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
February 26, 2021
CompletedResults Posted
Study results publicly available
May 10, 2022
CompletedMay 13, 2022
May 1, 2022
6.4 years
January 29, 2014
February 25, 2022
May 11, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival
In this outcome measure number of deaths during the study were reported.
Day 1 of study treatment up to date of death (within a maximum duration of 2102 days)
Secondary Outcomes (3)
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)
Change From Baseline in 6-Minute Walk Distance (6MWD) at Month 6
Baseline, Month 6
Change From Baseline in 6-Minute Walk Distance (6MWD) at Month 12
Baseline, Month 12
Study Arms (3)
Low dose
EXPERIMENTALMedium dose
EXPERIMENTALHigh dose
EXPERIMENTALInterventions
sildenafil citrate (PDE-5 inhibitor) 5 mg tablet TID until study treatment discontinued or end of study
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (82)
Emory University Investigational Drug Services
Atlanta, Georgia, 30322, United States
The Emory Clinic
Atlanta, Georgia, 30322, United States
Frederik Meijer Heart & Vascular Institute Cardiovascular Research
Grand Rapids, Michigan, 49503, United States
Spectrum Health Butterworth Hospital IDS Pharmacy
Grand Rapids, Michigan, 49503, United States
Spectrum Health Heart & Lung Specialized Care Clinic
Grand Rapids, Michigan, 49503, United States
Spectrum Health Hospitals
Grand Rapids, Michigan, 49503, United States
Spectrum Health Medical Group - Pulmonary Division
Grand Rapids, Michigan, 49546, United States
Spectrum Health
Grand Rapids, Michigan, 49546, United States
Robert V. Sibilia MD, Inc.
Wooster, Ohio, 44691, United States
UT Southwestern Medical School
Dallas, Texas, 75390-8550, United States
Aurora St. Luke's Medical Center
Milwaukee, Wisconsin, 53215, United States
St. Vincent's Hospital
Darlinghurst, New South Wales, 2010, Australia
Westmead Hospital
Westmead, New South Wales, 2145, Australia
Royal Brisbane & Women's Hospital
Herston, Queensland, 4029, Australia
Australian Respiratory and Sleep Medicine Institute
Bedford Park, South Australia, 5042, Australia
University Hospital of Mont-Godinne
Yvoir, 5530, Belgium
University Clinical Center of the Republic of Srpska
Banja Luka, B&h/republic of Srpska, 78000, Bosnia and Herzegovina
Clinical Center University Sarajevo
Sarajevo, Bosnia and Herzegovina/canton Sarajevo, 71000, Bosnia and Herzegovina
Health Institution Special Hospital "Medical Institute Bayer"
Tuzla, Canton Tuzla, 75000, Bosnia and Herzegovina
University Clinical Hospital Mostar
Mostar, Herzegovina-neretva Canton, 88000, Bosnia and Herzegovina
University Hospital Center Zagreb
Zagreb, 10 000, Croatia
University Hospital Dubrava
Zagreb, 10000, Croatia
Vseobecna fakultni nemocnice v Praze
Prague, Czech Republic, 128 08, Czechia
Fakultni nemocnice Olomouc
Olomouc, 779 00, Czechia
Institut Klinicke a Experimentalni Mediciny
Prague, 140 21, Czechia
DRK Kliniken Berlin, Westend
Berlin, 14050, Germany
Universitaetsklinikum der TU Dresden
Dresden, 01307, Germany
Universitatsklinikum TU Dresden
Dresden, 01307, Germany
Universitaetsmedizin Greifswald
Greifswald, 17475, Germany
Universitaetsklinikum Hamburg-Eppendorf
Hamburg, 20246, Germany
Thoraxklinik am Universitaetsklinikum Heidelberg
Heidelberg, 69126, Germany
Universitaetsklinikum Schleswig-Holstein
Lübeck, 23538, Germany
University General Hospital of Athens "Attikon"
Athens, Attica, 12462, Greece
University General Hospital of Alexandroupolis
Alexandroupoli, Evros, 68100, Greece
University General Hospital of Patras
Pátrai, 26504, Greece
University General Hospital of Thessaloniki AHEPA
Thessaloniki, 54636, Greece
Queen Mary Hospital
Hong Kong, Hong Kong
Prince of Wales Hospital
Shatin, New Territories, Hong Kong
The Chaim Sheba Medical Center
Tel Litwinsky, 5262000, Israel
Pauls Stradins Clinical University Hospital
Riga, LV-1002, Latvia
Hospital Sultanah Aminah
Johor Bahru, Johor, 80100, Malaysia
Hospital Sultanah Bahiyah
Alor Star, Kedah, 05460, Malaysia
Hospital Serdang
Kajang, Selangor, 43000, Malaysia
University Malaya Medical Centre
Kuala Lumpur, 59100, Malaysia
Centro De Prevencion Y Rehabilitacion De Enfermedades Pulmonares Crónicas
Monterrey, Nuevo León, 64460, Mexico
Centro de Desarrollo Biomedico
Mérida, Yucatán, 97070, Mexico
Centro de Estudios Clinicos de Queretaro S.C.
Querétaro, 76000, Mexico
Samodzielny Publiczny Szpital Kliniczny nr 4
Lublin, 20-954, Poland
Institutul Inimii ,,Niculae Stancioiu" Cluj Napoca
Cluj-Napoca, 400001, Romania
Institutul de Urgenta pentru Boli Cardiovasculare si Transplant Targu-Mures
Târgu Mureş, 540136, Romania
FSBI "V.A. Almazov National Medical Research Center"
Saint Petersburg, Russian Federation, 197341, Russia
FSBI "Research Institute of complex problems of cardiovascular diseases"
Kemerovo, 650002, Russia
FSBI Scientific Research Institute of Pulmonology of FMBA
Moscow, 105077, Russia
FSBI "E.Meshalkin National medical research center"
Novosibirsk, 630055, Russia
Institute for Cardiovascular disease of Vojvodina
Kamenitz, Vojvodina, 21204, Serbia
Institute for Pulmonary Diseases of Vojvodina
Kamenitz, Vojvodina, 21204, Serbia
Clinical Center of Serbia
Belgrade, 11000, Serbia
University Medical Center Zvezdara
Belgrade, 11000, Serbia
Clinical Center Kragujevac
Kragujevac, 34 000, Serbia
National University Heart Centre, National University Hospital Singapore (NUHS)
Singapore, 119228, Singapore
Khoo Teck Puat Hospital
Singapore, 768828, Singapore
Center of Chest Diseases
Johannesburg, Gauteng, 2193, South Africa
Dr PG Williams Practice
Johannesburg, Gauteng, 2193, South Africa
Hospital Universitario Vall d´Hebrón
Barcelona, Catalonia, 08035, Spain
Faculty of Medicine, Chulalongkorn University
Pathumwan, Bangkok, 10330, Thailand
King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University
Pathumwan, Bangkok, 10330, Thailand
Division of Cardiology, Department of Medicine, Faculty of Medicine, Khon Kaen University
Muang District, Changwat Khon Kaen, 40002, Thailand
Queen Sirikit Heart Center of the Northeast, Khon Kaen University
Muang District, Changwat Khon Kaen, 40002, Thailand
Srinagarind Hospital, Faculty of Medicine, Khon Kaen University
Muang District, Changwat Khon Kaen, 40002, Thailand
Maharaj Nakorn Chiang Mai Hospital
Muang, Chiang Mai, 50200, Thailand
Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University
Sripoom Sub-district, Muang, Chiang Mai, 50200, Thailand
Bakirkoy Dr. Sadi Konuk Training and Research Hospital
Istanbul, Bakirkoy, 34147, Turkey (Türkiye)
Istanbul University Cerrahpasa Medical Faculty
Istanbul, Fatih, 34096, Turkey (Türkiye)
Istanbul University Haseki Cardiology Institute
Istanbul, Fatih, 34096, Turkey (Türkiye)
Dokuz Eylul Üniversitesi Tıp Fakültesi Kardiyoloji Bilim Dalı
Izmir, Inciralti, 35340, Turkey (Türkiye)
Marmara University Pendik Training and Research Hospital
Istanbul, Pendik, 34899, Turkey (Türkiye)
Komunalne nekomertsiine pidpryiemstvo
Kharkiv, 61176, Ukraine
Komunalne nekomertsiine pidpryiemstvo Oleksandrivska klinichna likarnia m. Kyieva
Kyiv, 01601, Ukraine
Komunalne nekomertsiine pidpryiemstvo
Kyiv, 03115, Ukraine
Derzhavna ustanova Natsionalnyi naukovyi tsentr
Kyiv, 03680, Ukraine
Komunalne pidpryiemstvo "Dnipropetrovskyi oblasnyi klinichnyi tsentr kardiolohii ta kardiokhirurhii"
M. Dnipro, 49044, Ukraine
Komunalne nekomertsiine pidpryiemstvo
Uzhhorod, 88000, Ukraine
Related Publications (1)
Hoeper MM, Ewert R, Jansa P, Sirenko Y, Skride A, Balagtas C, Hackley S, Vogt S, Abreu P, Haughie S, Hassan T, Oudiz RJ. Randomized, Multicenter Study to Assess the Effects of Different Doses of Sildenafil on Mortality in Adults With Pulmonary Arterial Hypertension. Circulation. 2024 Jun 18;149(25):1949-1959. doi: 10.1161/CIRCULATIONAHA.123.068107. Epub 2024 May 16.
PMID: 38752352DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Study was terminated by Sponsor at recommendation of Data Monitoring Committee after completion of first interim analysis as primary objective was met. For OS and clinical worsening(CW) endpoints, significance level was adjusted to allow for interim analysis. Hence 99.7% CIs were presented instead of 95% CIs. 80mg vs 5mg comparison for OS was primary and it was key secondary for CW. CIs for other dose comparisons for these endpoints were nominal. P-values and CIs for other endpoints were nominal
Results Point of Contact
- Title
- Pfizer ClinicalTrials.gov Call Center
- Organization
- Pfizer Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 29, 2014
First Posted
February 12, 2014
Study Start
September 22, 2014
Primary Completion
February 26, 2021
Study Completion
February 26, 2021
Last Updated
May 13, 2022
Results First Posted
May 10, 2022
Record last verified: 2022-05
Data Sharing
- IPD Sharing
- Will share
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.