To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.
- Registration Number
- NCT00430716
- Lead Sponsor
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
- Brief Summary
To demonstrate a dose response for 1 mg, 5 mg and 20 mg TID oral sildenafil for the treatment of subjects with PAH.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 130
- Subjects with PAH (i.e. IPAH or secondary to connective tissue disease or with surgical repair of ASD, VSD, PDA, aorto-pulmonary window) whose baseline six minute walk test distance is >/= 100 m and </= 450 m.
- Subjects with a mean pulmonary artery pressure of >/= 25 mmHg and a pulmonary artery wedge pressure of </= 15 mmHg at rest via right heart catheterization performed within 12 weeks prior to randomization.
- Subjects whose 6 Minute Walk Distance may be limited by conditions other than PAH related dyspnoea or fatigue, e.g. claudication from vascular insufficiency or significant arthritis.
- Subjects who are currently receiving any forms of chronic treatment for PAH such as prostacyclin, PDE-5 inhibitors, endothelin-receptor antagonists, nitrates or nitric oxide donors (e.g. arginine supplement, nicorandil) in any form, protease inhibitors such as ritonavir and saquinavir, ketoconazole, itraconazole, and alpha blockers. Subjects previously receiving any of these drugs must have stopped use for a period of at least 1 month prior to screening, except in the case of bosentan or prostacyclin (3 months).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sildenafil High dose Sildenafil citrate - Sildenafil Low dose Sildenafil citrate - Sildenafil medium dose Sildenafil citrate - Sildenafil - Open label Phase Sildenafil citrate Open label extension from week 12 to week 24.
- Primary Outcome Measures
Name Time Method Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 12 Baseline and Week 12 6 MWT 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. Continuous pulse oximetry was conducted during the test for safety.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 12 Baseline and Week 12 mPAP was measured using a pressure transducer positioned at the mid-axillary line.
Number of Participants With Clinical Worsening Baseline through Week 12 Clinical worsening was defined as death; or lung transplantation; or hospitalization due to pulmonary hypertension; or initiation of prostacyclin therapy; or initiation of endothelin receptor antagonist therapy. (PAH=pulmonary arterial hypertension) Due to very low number of events of clinical worsening reported, the median days to clinical worsening could not be estimated.
Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12 Baseline and Week 12 Pulmonary arterial hypertension (PAH) Criteria for WHO Class: Class I (Participants without resulting limitation of physical activity);Class II (Participants with slight limitation of physical activity though comfortable at rest);Class III (Participants with marked limitation of physical activity,though comfortable at rest);Class IV(Participants with inability to carry out any physical activity without symptoms,manifest signs of right heart failure; dyspnoea and/or fatigue may even be present at rest; and discomfort is increased by any physical activity).
Change From Baseline in B-Type Natriuretic Peptide (BNP) at Week 12 Baseline and Week 12 BNP is a non-invasive biomarker and an indicator of progression of PAH/ right ventricular dysfunction in participants with PAH.
Change From Baseline in Pro-BNP at Week 12 Baseline and Week 12 Pro- BNP which is a precursor of BNP, is a non-invasive biomarker and an indicator of progression of PAH / RV dysfunction in participants with PAH.
Change From Baseline in TAPSE Measurement at Week 12 Baseline and Week 12 Tricuspid annular plane systolic excursion (TAPSE) was measured as the total displacement of the tricuspid annulus in cm from end diastole to end systole.TAPSE is an indicator of progression of PAH /right ventricular dysfunction.
The baseline data for 33 participants were measured incorrectly and the results from the 33 participants (both baseline and post-baseline) were excluded from the analysis.Change From Baseline in BORG Dyspnoea Score at Week 12 Baseline and Week 12 BORG dyspnoea scale is a 10-point scale where following scores stands for severity of dyspnoea: 0 (no breathlessness at all); 0.5 (very very slight \[just noticeable\]); 1 (very slight); 2 (slight breathlessness); 3 (moderate); 4 (some what severe); 5 (severe breathlessness); 7 (very severe breathlessness); 9 (very very severe \[almost maximum\] and 10 (maximum).
Trial Locations
- Locations (45)
Erasmus MC
🇳🇱Rotterdam, Netherlands
Hospital São Lucas da PUCRS
🇧🇷Porto Alegre, RS, Brazil
Care Hospital, The Institute of Medical Sciences
🇮🇳Hyderabad, Andhra Pradesh, India
Instituto Dante Pazzanese de Cardiologia
🇧🇷Sao Paulo, SP, Brazil
Norfolk and Norwich University Hospital
🇬🇧Norwich, Norfolk, United Kingdom
Peta mnogoprofilna bolnitsa za aktivno lechenie, Klinika po kardiologia
🇧🇬Sofia, Bulgaria
Metro Multispeciality Hospital
🇮🇳Noida, Uttar Pradesh, India
IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
VU Medisch Centrum / afdeling Longziekten
🇳🇱Amsterdam, Netherlands
Unita' di Ipertensione Polmonare, Dipartimento di Scienze Respiratorie e Cardiovascolari
🇮🇹Roma, Italy
National Heart Institute
🇲🇾Kuala Lumpur, Malaysia
Philippine General Hospital
🇵ðŸ‡Manila City, Philippines
Krakowski Szpital Specjalistyczny Im. Jana Pawla II w Krakowie
🇵🇱Krakow, Poland
Samodzielny Publiczny Zaklad Opieki Zdrowotnej, Slaskie Centrum Chorob Serca
🇵🇱Zabrze, Poland
Department of Medicine,
🇹ðŸ‡Bangkok, Thailand
Philippine Heart Center
🇵ðŸ‡Quezon City, Philippines
Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes
🇷🇴Timisoara, Timis, Romania
Spitalul Clinic de Pneumoftiziologie
🇷🇴Iasi, Romania
Scientific Center of Cardiovascular surgery n.a. A.N.Bakoulev RAMS
🇷🇺Moscow, Russian Federation
Atlanta Institute for Medical Research, Inc.
🇺🇸Decatur, Georgia, United States
The University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Pulmonary Associates of Richmond, Inc.
🇺🇸Richmond, Virginia, United States
Mnogoprofilna bolnitsa za aktivno lechenie i speshna meditsina "N.I.Pirogov"
🇧🇬Sofia, Bulgaria
St. John's Medical College Hospital
🇮🇳Bangalore, Karnataka, India
P. Stradins Clinical University Hospital / Latvian Centre of Cardilogy
🇱🇻Riga, Latvia
The Care Group, LLC
🇺🇸Indianapolis, Indiana, United States
Baylor College of Medicine Pulmonary Section
🇺🇸Houston, Texas, United States
St. Luke's Episcopal Hospital
🇺🇸Houston, Texas, United States
Medical College of Georgia
🇺🇸Augusta, Georgia, United States
University of Utah Sciences Center
🇺🇸Salt Lake City, Utah, United States
Arizona Pulmonary Specialists, LTD
🇺🇸Phoenix, Arizona, United States
Mehta Hospital & Cardiopulmonary Care Center
🇮🇳Ahmedabad, Gujarat, India
Bankers Heart Institute
🇮🇳Vadodara, Gujarat, India
Attikon Hospital
🇬🇷Haidari, Athens, Greece
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
Shanghai Pulmonology Hospital
🇨🇳Shanghai, China
Beijing Shijitan Hospital
🇨🇳Beijing, China
Room 224A Sir William Leech Centre
🇬🇧Newcastle Upon Tyne, Tyne and Wear, United Kingdom
CJW Chippenham Medical Center
🇺🇸Richmond, Virginia, United States
Division of Rheumatology Allergy and Immunology, Department of Medicine, Faculty of Medicine
🇹ðŸ‡Amphoe Mueang, Khon Kaen, Thailand
Presbyterian Hospital
🇺🇸Charlotte, North Carolina, United States
Mid Carolina Cardiology
🇺🇸Charlotte, North Carolina, United States
Chicago Heart Institute
🇺🇸Elk Grove Village, Illinois, United States
Virginia Cardiovascular Specialists
🇺🇸Richmond, Virginia, United States
Cardiovascular Associates of Virginia
🇺🇸Richmond, Virginia, United States