Effects of Oral Sildenafil on Mortality in Adults With PAH (AFFILIATE)

May 11, 2022 updated by: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

A MULTINATIONAL, MULTICENTER STUDY TO ASSESS THE EFFECTS OF ORAL SILDENAFIL ON MORTALITY IN ADULTS WITH PULMONARY ARTERIAL HYPERTENSION (PAH)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
385

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Darlinghurst, New South Wales, Australia, 2010
        • St. Vincent's Hospital
      • Westmead, New South Wales, Australia, 2145
        • Westmead Hospital
    • Queensland
      • Herston, Queensland, Australia, 4029
        • Royal Brisbane & Women's Hospital
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
        • Australian Respiratory and Sleep Medicine Institute
  • Belgium
      • Yvoir, Belgium, 5530
        • University Hospital of Mont-Godinne
  • Bosnia and Herzegovina
    • B&h/republic OF Srpska
      • Banja Luka, B&h/republic OF Srpska, Bosnia and Herzegovina, 78000
        • University Clinical Center of the Republic of Srpska
    • Bosnia AND Herzegovina/canton Sarajevo
      • Sarajevo, Bosnia AND Herzegovina/canton Sarajevo, Bosnia and Herzegovina, 71000
        • Clinical Center University Sarajevo
    • Canton Tuzla
      • Tuzla, Canton Tuzla, Bosnia and Herzegovina, 75000
        • Health Institution Special Hospital "Medical Institute Bayer"
    • Herzegovina-neretva Canton
      • Mostar, Herzegovina-neretva Canton, Bosnia and Herzegovina, 88000
        • University Clinical Hospital Mostar
  • Croatia
      • Zagreb, Croatia, 10000
        • University Hospital Dubrava
      • Zagreb, Croatia, 10 000
        • University Hospital Center Zagreb
  • Czechia
      • Olomouc, Czechia, 779 00
        • Fakultni nemocnice Olomouc
      • Praha 4, Czechia, 140 21
        • Institut Klinické a Experimentální Medicíny
    • Czech Republic
      • Praha 2, Czech Republic, Czechia, 128 08
        • Vseobecna Fakultni Nemocnice v Praze
  • Germany
      • Berlin, Germany, 14050
        • DRK Kliniken Berlin, Westend
      • Dresden, Germany, 01307
        • Universitaetsklinikum der TU Dresden
      • Dresden, Germany, 01307
        • Universitätsklinikum TU Dresden
      • Greifswald, Germany, 17475
        • Universitaetsmedizin Greifswald
      • Hamburg, Germany, 20246
        • Universitaetsklinikum Hamburg-Eppendorf
      • Heidelberg, Germany, 69126
        • Thoraxklinik am Universitaetsklinikum Heidelberg
      • Luebeck, Germany, 23538
        • Universitaetsklinikum Schleswig-Holstein
  • Greece
      • Patras, Greece, 26504
        • University General Hospital of Patras
      • Thessaloniki, Greece, 54636
        • University General Hospital of Thessaloniki AHEPA
    • Attiki
      • Athens, Attiki, Greece, 12462
        • University General Hospital of Athens "Attikon"
    • Evros
      • Alexandroupolis, Evros, Greece, 68100
        • University General Hospital of Alexandroupolis
  • Hong Kong
      • Hong Kong, Hong Kong
        • Queen Mary Hospital
      • Shatin, New Territories, Hong Kong
        • Prince of Wales Hospital
  • Israel
      • Tel-Hashomer, Israel, 5262000
        • The Chaim Sheba Medical Center
  • Latvia
      • Riga, Latvia, LV-1002
        • Pauls Stradins Clinical University Hospital
  • Malaysia
      • Kuala Lumpur, Malaysia, 59100
        • University Malaya Medical Centre
    • Johor
      • Johor Bahru, Johor, Malaysia, 80100
        • Hospital Sultanah Aminah
    • Kedah
      • Alor Setar, Kedah, Malaysia, 05460
        • Hospital Sultanah Bahiyah
    • Selangor
      • Kajang, Selangor, Malaysia, 43000
        • Hospital Serdang
  • Mexico
      • Queretaro, Mexico, 76000
        • Centro de Estudios Clinicos de Querétaro S.C.
    • Nuevo LEÓN
      • Monterrey, Nuevo LEÓN, Mexico, 64460
        • Centro De Prevencion Y Rehabilitacion De Enfermedades Pulmonares Crónicas
    • Yucatan
      • Merida, Yucatan, Mexico, 97070
        • Centro de Desarrollo Biomedico
  • Poland
      • Lublin, Poland, 20-954
        • Samodzielny Publiczny Szpital Kliniczny nr 4
  • Romania
      • Cluj-Napoca, Romania, 400001
        • Institutul Inimii ,,Niculae Stancioiu" Cluj Napoca
      • Targu-Mures, Romania, 540136
        • Institutul de Urgenta pentru Boli Cardiovasculare si Transplant Targu-Mures
  • Russian Federation
      • Kemerovo, Russian Federation, 650002
        • FSBI "Research Institute of complex problems of cardiovascular diseases"
      • Moscow, Russian Federation, 105077
        • FSBI Scientific Research Institute of Pulmonology of FMBA
      • Novosibirsk, Russian Federation, 630055
        • FSBI "E.Meshalkin National medical research center"
      • St. Petersburg, Russian Federation, 197341
        • FSBI "V.A. Almazov National Medical Research Center"
  • Serbia
      • Belgrade, Serbia, 11000
        • Clinical Center of Serbia
      • Belgrade, Serbia, 11000
        • University Medical Center Zvezdara
      • Kragujevac, Serbia, 34 000
        • Clinical center Kragujevac
    • Vojvodina
      • Sremska Kamenica, Vojvodina, Serbia, 21204
        • Institute for Cardiovascular Disease of Vojvodina
      • Sremska Kamenica, Vojvodina, Serbia, 21204
        • Institute for Pulmonary Diseases of Vojvodina
  • Singapore
      • Singapore, Singapore, 768828
        • Khoo Teck Puat Hospital
      • Singapore, Singapore, 119228
        • National University Heart Centre, National University Hospital Singapore (NUHS)
  • South Africa
    • Gauteng
      • Johannesburg, Gauteng, South Africa, 2193
        • Center of Chest Diseases
      • Johannesburg, Gauteng, South Africa, 2193
        • Dr PG Williams Practice
  • Spain
    • Cataluña
      • Barcelona, Cataluña, Spain, 08035
        • Hospital Universitario Vall d´Hebrón
  • Thailand
    • Bangkok
      • Pathumwan, Bangkok, Thailand, 10330
        • Faculty of Medicine, Chulalongkorn University
      • Pathumwan, Bangkok, Thailand, 10330
        • King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University
    • Chiang MAI
      • Muang, Chiang MAI, Thailand, 50200
        • Maharaj Nakorn Chiang Mai Hospital
      • Sripoom Sub-district, Muang, Chiang MAI, Thailand, 50200
        • Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University
    • Khon Kaen
      • Muang District, Khon Kaen, Thailand, 40002
        • Division of Cardiology, Department of Medicine, Faculty of Medicine, Khon Kaen University
      • Muang District, Khon Kaen, Thailand, 40002
        • Queen Sirikit Heart Center of the Northeast, Khon Kaen University
      • Muang District, Khon Kaen, Thailand, 40002
        • Srinagarind Hospital, Faculty of Medicine, Khon Kaen University
  • Turkey
    • Bakirkoy
      • Istanbul, Bakirkoy, Turkey, 34147
        • Bakirkoy Dr. Sadi Konuk Training and Research Hospital
    • Fatih
      • Istanbul, Fatih, Turkey, 34096
        • Istanbul University Cerrahpasa Medical Faculty
      • Istanbul, Fatih, Turkey, 34096
        • Istanbul University Haseki Cardiology Institute
    • Inciralti
      • Izmir, Inciralti, Turkey, 35340
        • Dokuz Eylul Üniversitesi Tıp Fakültesi Kardiyoloji Bilim Dalı
    • Pendik
      • Istanbul, Pendik, Turkey, 34899
        • Marmara University Pendik Training and Research Hospital
  • Ukraine
      • Kharkiv,, Ukraine, 61176
        • Komunalne nekomertsiine pidpryiemstvo
      • Kyiv, Ukraine, 01601
        • Komunalne nekomertsiine pidpryiemstvo Oleksandrivska klinichna likarnia m. Kyieva
      • Kyiv, Ukraine, 03115
        • Komunalne nekomertsiine pidpryiemstvo
      • Kyiv, Ukraine, 03680
        • Derzhavna ustanova Natsionalnyi naukovyi tsentr
      • M. Dnipro, Ukraine, 49044
        • Komunalne pidpryiemstvo "Dnipropetrovskyi oblasnyi klinichnyi tsentr kardiolohii ta kardiokhirurhii"
      • Uzhhorod,, Ukraine, 88000
        • Komunalne nekomertsiine pidpryiemstvo
  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • The Emory Clinic
      • Atlanta, Georgia, United States, 30322
        • Emory University Investigational Drug Services
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • Spectrum Health Hospitals
      • Grand Rapids, Michigan, United States, 49546
        • Spectrum Health
      • Grand Rapids, Michigan, United States, 49503
        • Frederik Meijer Heart & Vascular Institute Cardiovascular Research
      • Grand Rapids, Michigan, United States, 49503
        • Spectrum Health Butterworth Hospital IDS Pharmacy
      • Grand Rapids, Michigan, United States, 49503
        • Spectrum Health Heart & Lung Specialized Care Clinic
      • Grand Rapids, Michigan, United States, 49546
        • Spectrum Health Medical Group - Pulmonary Division
    • Ohio
      • Wooster, Ohio, United States, 44691
        • Robert V. Sibilia MD, Inc.
    • Texas
      • Dallas, Texas, United States, 75390-8550
        • UT Southwestern Medical School
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53215
        • Aurora St. Luke's Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Low dose
Drug: sildenafil citrate
sildenafil citrate (PDE-5 inhibitor) 5 mg tablet TID until study treatment discontinued or end of study
Other Names:
  • Revatio
Drug: sildenafil citrate
sildenafil citrate (PDE-5 inhibitor) 20 mg tablet TID until study treatment discontinued or end of study
Other Names:
  • Revatio
Drug: sildenafil citrate
sildenafil citrate (PDE-5 inhibitor) 80 mg tablet TID until study treatment discontinued or end of study
Other Names:
  • Revatio
Experimental: High dose
Drug: sildenafil citrate
sildenafil citrate (PDE-5 inhibitor) 5 mg tablet TID until study treatment discontinued or end of study
Other Names:
  • Revatio
Drug: sildenafil citrate
sildenafil citrate (PDE-5 inhibitor) 20 mg tablet TID until study treatment discontinued or end of study
Other Names:
  • Revatio
Drug: sildenafil citrate
sildenafil citrate (PDE-5 inhibitor) 80 mg tablet TID until study treatment discontinued or end of study
Other Names:
  • Revatio
Experimental: Medium dose
Drug: sildenafil citrate
sildenafil citrate (PDE-5 inhibitor) 5 mg tablet TID until study treatment discontinued or end of study
Other Names:
  • Revatio
Drug: sildenafil citrate
sildenafil citrate (PDE-5 inhibitor) 20 mg tablet TID until study treatment discontinued or end of study
Other Names:
  • Revatio
Drug: sildenafil citrate
sildenafil citrate (PDE-5 inhibitor) 80 mg tablet TID until study treatment discontinued or end of study
Other Names:
  • Revatio

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 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.
Day 1 of study treatment up to date of death (within a maximum duration of 2102 days)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Clinical Worsening Events
Time Frame: 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.
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
Time Frame: 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.
Baseline, Month 6
Change From Baseline in 6-Minute Walk Distance (6MWD) at Month 12
Time Frame: 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.
Baseline, Month 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 22, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 26, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 26, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 29, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 10, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 12, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 13, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 11, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • A1481324
  • 2013-004362-34 (EudraCT Number)
  • AFFILIATE (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings