Effects of Oral Sildenafil on Mortality in Adults With PAH

Pulmonary Arterial Hypertension Clinical Trial

— AFFILIATE  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02060487
• Other study ID #: A1481324
• Secondary ID: 2013-004362-34AF
• Status: Terminated
• Phase: Phase 4
• Start date: September 22, 2014
• Est. completion date: February 26, 2021

Study information

• Verified date: May 2022
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 385
• Est. completion date: February 26, 2021
• Est. primary completion date: February 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• sildenafil citrate
sildenafil citrate (PDE-5 inhibitor) 5 mg tablet TID until study treatment discontinued or end of study
• sildenafil citrate
sildenafil citrate (PDE-5 inhibitor) 20 mg tablet TID until study treatment discontinued or end of study
• sildenafil citrate
sildenafil citrate (PDE-5 inhibitor) 80 mg tablet TID until study treatment discontinued or end of study

Locations

Country	Name	City	State
Australia	Australian Respiratory and Sleep Medicine Institute	Bedford Park	South Australia
Australia	St. Vincent's Hospital	Darlinghurst	New South Wales
Australia	Royal Brisbane & Women's Hospital	Herston	Queensland
Australia	Westmead Hospital	Westmead	New South Wales
Belgium	University Hospital of Mont-Godinne	Yvoir
Bosnia and Herzegovina	University Clinical Center of the Republic of Srpska	Banja Luka	B&h/republic OF Srpska
Bosnia and Herzegovina	University Clinical Hospital Mostar	Mostar	Herzegovina-neretva Canton
Bosnia and Herzegovina	Clinical Center University Sarajevo	Sarajevo	Bosnia AND Herzegovina/canton Sarajevo
Bosnia and Herzegovina	Health Institution Special Hospital "Medical Institute Bayer"	Tuzla	Canton Tuzla
Croatia	University Hospital Center Zagreb	Zagreb
Croatia	University Hospital Dubrava	Zagreb
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2	Czech Republic
Czechia	Institut Klinicke a Experimentalni Mediciny	Praha 4
Germany	DRK Kliniken Berlin, Westend	Berlin
Germany	Universitaetsklinikum der TU Dresden	Dresden
Germany	Universitatsklinikum TU Dresden	Dresden
Germany	Universitaetsmedizin Greifswald	Greifswald
Germany	Universitaetsklinikum Hamburg-Eppendorf	Hamburg
Germany	Thoraxklinik am Universitaetsklinikum Heidelberg	Heidelberg
Germany	Universitaetsklinikum Schleswig-Holstein	Luebeck
Greece	University General Hospital of Alexandroupolis	Alexandroupolis	Evros
Greece	University General Hospital of Athens "Attikon"	Athens	Attiki
Greece	University General Hospital of Patras	Patras
Greece	University General Hospital of Thessaloniki AHEPA	Thessaloniki
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Prince of Wales Hospital	Shatin, New Territories
Israel	The Chaim Sheba Medical Center	Tel-Hashomer
Latvia	Pauls Stradins Clinical University Hospital	Riga
Malaysia	Hospital Sultanah Bahiyah	Alor Setar	Kedah
Malaysia	Hospital Sultanah Aminah	Johor Bahru	Johor
Malaysia	Hospital Serdang	Kajang	Selangor
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Mexico	Centro de Desarrollo Biomedico	Merida	Yucatan
Mexico	Centro De Prevencion Y Rehabilitacion De Enfermedades Pulmonares Crónicas	Monterrey	Nuevo LEÓN
Mexico	Centro de Estudios Clinicos de Queretaro S.C.	Queretaro
Poland	Samodzielny Publiczny Szpital Kliniczny nr 4	Lublin
Romania	Institutul Inimii ,,Niculae Stancioiu" Cluj Napoca	Cluj-Napoca
Romania	Institutul de Urgenta pentru Boli Cardiovasculare si Transplant Targu-Mures	Targu-Mures
Russian Federation	FSBI "Research Institute of complex problems of cardiovascular diseases"	Kemerovo
Russian Federation	FSBI Scientific Research Institute of Pulmonology of FMBA	Moscow
Russian Federation	FSBI "E.Meshalkin National medical research center"	Novosibirsk
Russian Federation	FSBI "V.A. Almazov National Medical Research Center"	St. Petersburg
Serbia	Clinical Center of Serbia	Belgrade
Serbia	University Medical Center Zvezdara	Belgrade
Serbia	Clinical Center Kragujevac	Kragujevac
Serbia	Institute for Cardiovascular disease of Vojvodina	Sremska Kamenica	Vojvodina
Serbia	Institute for Pulmonary Diseases of Vojvodina	Sremska Kamenica	Vojvodina
Singapore	Khoo Teck Puat Hospital	Singapore
Singapore	National University Heart Centre, National University Hospital Singapore (NUHS)	Singapore
South Africa	Center of Chest Diseases	Johannesburg	Gauteng
South Africa	Dr PG Williams Practice	Johannesburg	Gauteng
Spain	Hospital Universitario Vall d´Hebrón	Barcelona	Cataluña
Thailand	Maharaj Nakorn Chiang Mai Hospital	Muang	Chiang MAI
Thailand	Division of Cardiology, Department of Medicine, Faculty of Medicine, Khon Kaen University	Muang District	Khon Kaen
Thailand	Queen Sirikit Heart Center of the Northeast, Khon Kaen University	Muang District	Khon Kaen
Thailand	Srinagarind Hospital, Faculty of Medicine, Khon Kaen University	Muang District	Khon Kaen
Thailand	Faculty of Medicine, Chulalongkorn University	Pathumwan	Bangkok
Thailand	King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University	Pathumwan	Bangkok
Thailand	Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University	Sripoom Sub-district, Muang	Chiang MAI
Turkey	Bakirkoy Dr. Sadi Konuk Training and Research Hospital	Istanbul	Bakirkoy
Turkey	Istanbul University Cerrahpasa Medical Faculty	Istanbul	Fatih
Turkey	Istanbul University Haseki Cardiology Institute	Istanbul	Fatih
Turkey	Marmara University Pendik Training and Research Hospital	Istanbul	Pendik
Turkey	Dokuz Eylul Üniversitesi Tip Fakültesi Kardiyoloji Bilim Dali	Izmir	Inciralti
Ukraine	Komunalne nekomertsiine pidpryiemstvo	Kharkiv,
Ukraine	Derzhavna ustanova Natsionalnyi naukovyi tsentr	Kyiv
Ukraine	Komunalne nekomertsiine pidpryiemstvo	Kyiv
Ukraine	Komunalne nekomertsiine pidpryiemstvo Oleksandrivska klinichna likarnia m. Kyieva	Kyiv
Ukraine	Komunalne pidpryiemstvo "Dnipropetrovskyi oblasnyi klinichnyi tsentr kardiolohii ta kardiokhirurhii"	M. Dnipro
Ukraine	Komunalne nekomertsiine pidpryiemstvo	Uzhhorod,
United States	Emory University Investigational Drug Services	Atlanta	Georgia
United States	The Emory Clinic	Atlanta	Georgia
United States	UT Southwestern Medical School	Dallas	Texas
United States	Frederik Meijer Heart & Vascular Institute Cardiovascular Research	Grand Rapids	Michigan
United States	Spectrum Health	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	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Robert V. Sibilia MD, Inc.	Wooster	Ohio

Sponsors (1)

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

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Bosnia and Herzegovina,  Croatia,  Czechia,  Germany,  Greece,  Hong Kong,  Israel,  Latvia,  Malaysia,  Mexico,  Poland,  Romania,  Russian Federation,  Serbia,  Singapore,  South Africa,  Spain,  Thailand,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of Participants With Clinical Worsening Events	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)
Secondary	Change From Baseline in 6-Minute Walk Distance (6MWD) at 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
Secondary	Change From Baseline in 6-Minute Walk Distance (6MWD) at 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

External Links

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