MedPath

Effects of Oral Sildenafil on Mortality in Adults With PAH

Phase 4
Terminated
Conditions
Pulmonary Arterial Hypertension
Interventions
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
GroupInterventionDescription
Low dosesildenafil citrate-
High dosesildenafil citrate-
Medium dosesildenafil citrate-
Primary Outcome Measures
NameTimeMethod
Overall SurvivalDay 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
NameTimeMethod
Number of Participants With Clinical Worsening EventsDay 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 6Baseline, 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 12Baseline, 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)

Westmead Hospital

🇦🇺

Westmead, New South Wales, Australia

University Hospital of Mont-Godinne

🇧🇪

Yvoir, Belgium

FSBI Scientific Research Institute of Pulmonology of FMBA

🇷🇺

Moscow, Russian Federation

Universitaetsmedizin Greifswald

🇩🇪

Greifswald, Germany

FSBI "E.Meshalkin National medical research center"

🇷🇺

Novosibirsk, Russian Federation

FSBI "V.A. Almazov National Medical Research Center"

🇷🇺

St. Petersburg, Russian Federation

Health Institution Special Hospital "Medical Institute Bayer"

🇧🇦

Tuzla, Canton Tuzla, Bosnia and Herzegovina

Spectrum Health Heart & Lung Specialized Care Clinic

🇺🇸

Grand Rapids, Michigan, United States

Robert V. Sibilia MD, Inc.

🇺🇸

Wooster, Ohio, United States

Dr PG Williams Practice

🇿🇦

Johannesburg, Gauteng, South Africa

UT Southwestern Medical School

🇺🇸

Dallas, Texas, United States

Clinical Center University Sarajevo

🇧🇦

Sarajevo, Bosnia AND Herzegovina/canton Sarajevo, Bosnia and Herzegovina

Centro de Desarrollo Biomedico

🇲🇽

Merida, Yucatan, Mexico

Institutul Inimii ,,Niculae Stancioiu" Cluj Napoca

🇷🇴

Cluj-Napoca, Romania

Universitaetsklinikum Schleswig-Holstein

🇩🇪

Luebeck, Germany

Institut Klinicke a Experimentalni Mediciny

🇨🇿

Praha 4, Czechia

Clinical Center Kragujevac

🇷🇸

Kragujevac, Serbia

Spectrum Health Butterworth Hospital IDS Pharmacy

🇺🇸

Grand Rapids, Michigan, United States

Aurora St. Luke's Medical Center

🇺🇸

Milwaukee, Wisconsin, United States

Universitaetsklinikum Hamburg-Eppendorf

🇩🇪

Hamburg, Germany

Universitatsklinikum TU Dresden

🇩🇪

Dresden, Germany

Fakultni nemocnice Olomouc

🇨🇿

Olomouc, Czechia

Universitaetsklinikum der TU Dresden

🇩🇪

Dresden, Germany

Dokuz Eylul Üniversitesi Tıp Fakültesi Kardiyoloji Bilim Dalı

🇹🇷

Izmir, Inciralti, Turkey

The Chaim Sheba Medical Center

🇮🇱

Tel-Hashomer, Israel

University Hospital Center Zagreb

🇭🇷

Zagreb, Croatia

University Hospital Dubrava

🇭🇷

Zagreb, Croatia

DRK Kliniken Berlin, Westend

🇩🇪

Berlin, Germany

Faculty of Medicine, Chulalongkorn University

🇹🇭

Pathumwan, Bangkok, Thailand

Hospital Sultanah Aminah

🇲🇾

Johor Bahru, Johor, Malaysia

King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University

🇹🇭

Pathumwan, Bangkok, Thailand

Queen Sirikit Heart Center of the Northeast, Khon Kaen University

🇹🇭

Muang District, Khon Kaen, Thailand

Division of Cardiology, Department of Medicine, Faculty of Medicine, Khon Kaen University

🇹🇭

Muang District, Khon Kaen, Thailand

Srinagarind Hospital, Faculty of Medicine, Khon Kaen University

🇹🇭

Muang District, Khon Kaen, Thailand

Emory University Investigational Drug Services

🇺🇸

Atlanta, Georgia, United States

Frederik Meijer Heart & Vascular Institute Cardiovascular Research

🇺🇸

Grand Rapids, Michigan, United States

The Emory Clinic

🇺🇸

Atlanta, Georgia, United States

Spectrum Health

🇺🇸

Grand Rapids, Michigan, United States

Spectrum Health Medical Group - Pulmonary Division

🇺🇸

Grand Rapids, Michigan, United States

St. Vincent's Hospital

🇦🇺

Darlinghurst, New South Wales, Australia

Australian Respiratory and Sleep Medicine Institute

🇦🇺

Bedford Park, South Australia, Australia

Royal Brisbane & Women's Hospital

🇦🇺

Herston, Queensland, Australia

Thoraxklinik am Universitaetsklinikum Heidelberg

🇩🇪

Heidelberg, Germany

Vseobecna fakultni nemocnice v Praze

🇨🇿

Praha 2, Czech Republic, Czechia

University General Hospital of Patras

🇬🇷

Patras, Greece

Hospital Sultanah Bahiyah

🇲🇾

Alor Setar, Kedah, Malaysia

FSBI "Research Institute of complex problems of cardiovascular diseases"

🇷🇺

Kemerovo, Russian Federation

Institute for Cardiovascular disease of Vojvodina

🇷🇸

Sremska Kamenica, Vojvodina, Serbia

University Medical Center Zvezdara

🇷🇸

Belgrade, Serbia

National University Heart Centre, National University Hospital Singapore (NUHS)

🇸🇬

Singapore, Singapore

Center of Chest Diseases

🇿🇦

Johannesburg, Gauteng, South Africa

Hospital Universitario Vall d´Hebrón

🇪🇸

Barcelona, Cataluña, Spain

Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University

🇹🇭

Sripoom Sub-district, Muang, Chiang MAI, Thailand

Bakirkoy Dr. Sadi Konuk Training and Research Hospital

🇹🇷

Istanbul, Bakirkoy, Turkey

Istanbul University Haseki Cardiology Institute

🇹🇷

Istanbul, Fatih, Turkey

Istanbul University Cerrahpasa Medical Faculty

🇹🇷

Istanbul, Fatih, Turkey

Komunalne nekomertsiine pidpryiemstvo

🇺🇦

Uzhhorod,, Ukraine

Marmara University Pendik Training and Research Hospital

🇹🇷

Istanbul, Pendik, Turkey

Komunalne nekomertsiine pidpryiemstvo Oleksandrivska klinichna likarnia m. Kyieva

🇺🇦

Kyiv, Ukraine

Derzhavna ustanova Natsionalnyi naukovyi tsentr

🇺🇦

Kyiv, Ukraine

Komunalne pidpryiemstvo "Dnipropetrovskyi oblasnyi klinichnyi tsentr kardiolohii ta kardiokhirurhii"

🇺🇦

M. Dnipro, Ukraine

Spectrum Health Hospitals

🇺🇸

Grand Rapids, Michigan, United States

Centro de Estudios Clinicos de Queretaro S.C.

🇲🇽

Queretaro, Mexico

Hospital Serdang

🇲🇾

Kajang, Selangor, Malaysia

University Malaya Medical Centre

🇲🇾

Kuala Lumpur, Malaysia

University Clinical Center of the Republic of Srpska

🇧🇦

Banja Luka, B&h/republic OF Srpska, Bosnia and Herzegovina

University General Hospital of Alexandroupolis

🇬🇷

Alexandroupolis, Evros, Greece

Queen Mary Hospital

🇭🇰

Hong Kong, Hong Kong

University General Hospital of Thessaloniki AHEPA

🇬🇷

Thessaloniki, Greece

Pauls Stradins Clinical University Hospital

🇱🇻

Riga, Latvia

Samodzielny Publiczny Szpital Kliniczny nr 4

🇵🇱

Lublin, Poland

Maharaj Nakorn Chiang Mai Hospital

🇹🇭

Muang, Chiang MAI, Thailand

University Clinical Hospital Mostar

🇧🇦

Mostar, Herzegovina-neretva Canton, Bosnia and Herzegovina

Institutul de Urgenta pentru Boli Cardiovasculare si Transplant Targu-Mures

🇷🇴

Targu-Mures, Romania

University General Hospital of Athens "Attikon"

🇬🇷

Athens, Attiki, Greece

Clinical Center of Serbia

🇷🇸

Belgrade, Serbia

Institute for Pulmonary Diseases of Vojvodina

🇷🇸

Sremska Kamenica, Vojvodina, Serbia

Khoo Teck Puat Hospital

🇸🇬

Singapore, Singapore

Centro De Prevencion Y Rehabilitacion De Enfermedades Pulmonares Crónicas

🇲🇽

Monterrey, Nuevo LEÓN, Mexico

Prince of Wales Hospital

🇭🇰

Shatin, New Territories, Hong Kong

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