To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.

Pulmonary Arterial Hypertension Clinical Trial

Official title:

A MULTINATIONAL, MULTICENTRE, RANDOMIZED, PARALLEL GROUP, DOUBLE-BLIND STUDY TO ASSESS THE EFFICACY AND SAFETY OF 1MG, 5MG AND 20 MG TID OF ORAL SILDENAFIL IN THE TREATMENT OF SUBJECTS AGED 18 YEARS AND OVER WITH PULMONARY ARTERIAL HYPERTENSION (PAH)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00430716
• Other study ID #: A1481244
• Secondary ID: 2006-006748-76
• Status: Terminated
• Phase: Phase 4
• Start date: April 8, 2008
• Est. completion date: May 25, 2010

Study information

• Verified date: December 2020
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To demonstrate a dose response for 1 mg, 5 mg and 20 mg TID oral sildenafil for the treatment of subjects with PAH.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 130
• Est. completion date: May 25, 2010
• Est. primary completion date: May 25, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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).

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Sildenafil citrate
oral, 20 mg, tid
• Sildenafil citrate
oral 1 mg, tid
• Sildenafil citrate
oral 5 mg, tid
• Sildenafil citrate
oral 20 mg, tid

Locations

Country	Name	City	State
Belgium	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven
Brazil	Hospital São Lucas da PUCRS	Porto Alegre	RS
Brazil	Instituto Dante Pazzanese de Cardiologia	Sao Paulo	SP
Bulgaria	Mnogoprofilna bolnitsa za aktivno lechenie i speshna meditsina "N.I.Pirogov"	Sofia
Bulgaria	Peta mnogoprofilna bolnitsa za aktivno lechenie, Klinika po kardiologia	Sofia
China	Beijing Shijitan Hospital	Beijing
China	Shanghai Pulmonology Hospital	Shanghai
Greece	Attikon Hospital	Haidari	Athens
India	Mehta Hospital & Cardiopulmonary Care Center	Ahmedabad	Gujarat
India	St. John's Medical College Hospital	Bangalore	Karnataka
India	Care Hospital, The Institute of Medical Sciences	Hyderabad	Andhra Pradesh
India	Metro Multispeciality Hospital	Noida	Uttar Pradesh
India	Bankers Heart Institute	Vadodara	Gujarat
Italy	IRCCS Policlinico San Matteo	Pavia
Italy	Unita' di Ipertensione Polmonare, Dipartimento di Scienze Respiratorie e Cardiovascolari	Roma
Latvia	P. Stradins Clinical University Hospital / Latvian Centre of Cardilogy	Riga
Malaysia	National Heart Institute	Kuala Lumpur
Netherlands	VU Medisch Centrum / afdeling Longziekten	Amsterdam
Netherlands	Erasmus MC	Rotterdam
Philippines	Philippine General Hospital	Manila City
Philippines	Philippine Heart Center	Quezon City
Poland	Krakowski Szpital Specjalistyczny Im. Jana Pawla II w Krakowie	Krakow
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej, Slaskie Centrum Chorob Serca	Zabrze
Romania	Spitalul Clinic de Pneumoftiziologie	Iasi
Romania	Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes	Timisoara	Timis
Russian Federation	Scientific Center of Cardiovascular surgery n.a. A.N.Bakoulev RAMS	Moscow
Russian Federation	Scientific Center of Cardiovascular surgery n.a. A.N.Bakoulev RAMS	Moscow
Thailand	Division of Rheumatology Allergy and Immunology, Department of Medicine, Faculty of Medicine	Amphoe Mueang	Khon Kaen
Thailand	Department of Medicine,	Bangkok
United Kingdom	Room 224A Sir William Leech Centre	Newcastle Upon Tyne	Tyne and Wear
United Kingdom	Norfolk and Norwich University Hospital	Norwich	Norfolk
United States	Medical College of Georgia	Augusta	Georgia
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Mid Carolina Cardiology	Charlotte	North Carolina
United States	Presbyterian Hospital	Charlotte	North Carolina
United States	Atlanta Institute for Medical Research, Inc.	Decatur	Georgia
United States	Chicago Heart Institute	Elk Grove Village	Illinois
United States	Baylor College of Medicine Pulmonary Section	Houston	Texas
United States	St. Luke's Episcopal Hospital	Houston	Texas
United States	The Care Group, LLC	Indianapolis	Indiana
United States	Arizona Pulmonary Specialists, LTD	Phoenix	Arizona
United States	Cardiovascular Associates of Virginia	Richmond	Virginia
United States	CJW Chippenham Medical Center	Richmond	Virginia
United States	Pulmonary Associates of Richmond, Inc.	Richmond	Virginia
United States	Virginia Cardiovascular Specialists	Richmond	Virginia
United States	University of Utah Sciences Center	Salt Lake City	Utah

Sponsors (1)

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

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Bulgaria,  China,  Greece,  India,  Italy,  Latvia,  Malaysia,  Netherlands,  Philippines,  Poland,  Romania,  Russian Federation,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at 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.	Baseline and Week 12
Secondary	Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 12	mPAP was measured using a pressure transducer positioned at the mid-axillary line.	Baseline and Week 12
Secondary	Number of Participants With Clinical Worsening	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.	Baseline through Week 12
Secondary	Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at 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).	Baseline and Week 12
Secondary	Change From Baseline in B-Type Natriuretic Peptide (BNP) at Week 12	BNP is a non-invasive biomarker and an indicator of progression of PAH/ right ventricular dysfunction in participants with PAH.	Baseline and Week 12
Secondary	Change From Baseline in Pro-BNP at 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.	Baseline and Week 12
Secondary	Change From Baseline in TAPSE Measurement at 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.	Baseline and Week 12
Secondary	Change From Baseline in BORG Dyspnoea Score at 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).	Baseline and Week 12

External Links

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