Pulmonary Arterial HypertensionPhase 4NCT00430716
To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.
A Phase 4 study testing Sildenafil citrate in people with Pulmonary Arterial Hypertension, run by Pfizer's Upjohn has merged with Mylan to form Viatris Inc. at 46 sites in 17 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Sildenafil citrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 46 sitesin 17 countries
- Study dates
- 8 Apr 2008to 25 May 2010
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
46 sites in 17 countries.
46 sites in 17 countries
United States15 sites
Medical College of Georgia
Augusta, Georgia, 30912
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Mid Carolina Cardiology
Charlotte, North Carolina, 28204
Presbyterian Hospital
Charlotte, North Carolina, 28204
Atlanta Institute for Medical Research, Inc.
Decatur, Georgia, 30030
Chicago Heart Institute
Elk Grove Village, Illinois, 60007
Baylor College of Medicine Pulmonary Section
Houston, Texas, 77030
St. Luke's Episcopal Hospital
Houston, Texas, 77030
The Care Group, LLC
Indianapolis, Indiana, 46260
Arizona Pulmonary Specialists, LTD
Phoenix, Arizona, 85013
CJW Chippenham Medical Center
Richmond, Virginia, 23225
Pulmonary Associates of Richmond, Inc.
Richmond, Virginia, 23225
Virginia Cardiovascular Specialists
Richmond, Virginia, 23225
Cardiovascular Associates of Virginia
Richmond, Virginia, 23230
University of Utah Sciences Center
Salt Lake City, Utah, 84132
India5 sites
Mehta Hospital & Cardiopulmonary Care Center
Ahmedabad, Gujarat, 380 054
St. John's Medical College Hospital
Bangalore, Karnataka, 560 034
Care Hospital, The Institute of Medical Sciences
Hyderabad, Andhra Pradesh, 500 001
Metro Multispeciality Hospital
Noida, Uttar Pradesh, 201301
Bankers Heart Institute
Vadodara, Gujarat, 390 015
Brazil2 sites
Hospital São Lucas da PUCRS
Porto Alegre, Rio Grande do Sul, 90610-000
Instituto Dante Pazzanese de Cardiologia
São Paulo, São Paulo, 04012-909
Bulgaria2 sites
Peta mnogoprofilna bolnitsa za aktivno lechenie, Klinika po kardiologia
Sofia, 1233
Mnogoprofilna bolnitsa za aktivno lechenie i speshna meditsina "N.I.Pirogov"
Sofia, 1606
China2 sites
Beijing Shijitan Hospital
Beijing, 100038
Shanghai Pulmonology Hospital
Shanghai, 200433
Italy2 sites
IRCCS Policlinico San Matteo
Pavia, 27100
Unita' di Ipertensione Polmonare, Dipartimento di Scienze Respiratorie e Cardiovascolari
Roma, 00161
Netherlands2 sites
VU Medisch Centrum / afdeling Longziekten
Amsterdam, 1081 HV
Erasmus MC
Rotterdam, 3015 GE
Philippines2 sites
Philippine General Hospital
Manila, 1000
Philippine Heart Center
Quezon City, 1100
Poland2 sites
Krakowski Szpital Specjalistyczny Im. Jana Pawla II w Krakowie
Krakow, 31-202
Samodzielny Publiczny Zaklad Opieki Zdrowotnej, Slaskie Centrum Chorob Serca
Zabrze, 41-800
Romania2 sites
Spitalul Clinic de Pneumoftiziologie
Iași, 700115
Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes
Timișoara, Timiș County
Russia2 sites
Scientific Center of Cardiovascular surgery n.a. A.N.Bakoulev RAMS
Moscow, 117931
Scientific Center of Cardiovascular surgery n.a. A.N.Bakoulev RAMS
Moscow, 121552
Thailand2 sites
Division of Rheumatology Allergy and Immunology, Department of Medicine, Faculty of Medicine
Amphoe Mueang, Changwat Khon Kaen, 40002
Department of Medicine,
Bangkok, 10330
United Kingdom2 sites
Room 224A Sir William Leech Centre
Newcastle upon Tyne, TYNE and WEAR, NE7 7DN
Norfolk and Norwich University Hospital
Norwich, Norfolk, NR4 7UY
Belgium1 site
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
Leuven, 3000
Latvia1 site
P. Stradins Clinical University Hospital / Latvian Centre of Cardilogy
Riga, LV - 1002
About this study
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)
To demonstrate a dose response for 1 mg, 5 mg and 20 mg TID oral sildenafil for the treatment of subjects with PAH.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Sildenafil citrate
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sildenafil citrateDrug
oral, 20 mg, tid
Sildenafil citrateDrug
oral 1 mg, tid
Sildenafil citrateDrug
oral 5 mg, tid
Sildenafil citrateDrug
oral 20 mg, tid
| Study group | Role | What they receive |
|---|---|---|
| Sildenafil High dose | Experimental | Not described Receives: Drug: Sildenafil citrate |
| Sildenafil Low dose | Experimental | Not described Receives: Drug: Sildenafil citrate |
| Sildenafil medium dose | Experimental | Not described Receives: Drug: Sildenafil citrate |
| Sildenafil - Open label Phase | Experimental | Open label extension from week 12 to week 24. Receives: Drug: Sildenafil citrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Week 12
Secondary outcomes (7)
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.
Measured: Baseline and Week 12
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.
Measured: Baseline through Week 12
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).
Measured: Baseline and Week 12
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.
Measured: Baseline and Week 12
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.
Measured: Baseline and Week 12
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.
Measured: Baseline and Week 12
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).
Measured: Baseline and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2007 (estimated)
- Study start8 Apr 2008
- Primary completion25 May 2010
- Study completion25 May 2010
Why it stopped: This study was terminated at the recommendation of an independent Data Monitoring Committee. The decision was not based on any safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00430716
- Sponsor's protocol ID
- A1481244
- Other IDs
- 2006-006748-76
- Status last verified
- Dec 2020
- First submitted
- 31 Jan 2007
- Last updated
- 22 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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.
Publications
Vizza CD, Sastry BK, Safdar Z, Harnisch L, Gao X, Zhang M, Lamba M, Jing ZC. Efficacy of 1, 5, and 20 mg oral sildenafil in the treatment of adults with pulmonary arterial hypertension: a randomized, double-blind study with open-label extension. BMC Pulm Med. 2017 Feb 23;17(1):44. doi: 10.1186/s12890-017-0374-x.
PubMed 28228114
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00430716
- Acronym / sponsor ID
- A1481244
- Conditions
- Pulmonary Arterial Hypertension
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was terminated at the recommendation of an independent Data Monitoring Committee. The decision was not based on any safety concerns.
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.Industry (pharma, biotech, devices)
- Study start
- 8 Apr 2008 (actual)
- Primary completion
- 25 May 2010 (actual)
- Study completion
- 25 May 2010 (actual)
- First posted
- 2 Feb 2007 (estimated)
- Results
- Posted 17 May 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To demonstrate a dose response for 1 mg, 5 mg and 20 mg TID oral sildenafil for the treatment of subjects with PAH.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Sildenafil High dose | Experimental | Drug: Sildenafil citrate |
| Sildenafil Low dose | Experimental | Drug: Sildenafil citrate |
| Sildenafil medium dose | Experimental | Drug: Sildenafil citrate |
| Sildenafil - Open label Phase | Experimental | Drug: Sildenafil citrateOpen label extension from week 12 to week 24. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (2 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sildenafil citrateoral, 20 mg, tid | Drug | Sildenafil High dose |
| Sildenafil citrateoral 1 mg, tid | Drug | Sildenafil Low dose |
| Sildenafil citrateoral 5 mg, tid | Drug | Sildenafil medium dose |
| Sildenafil citrateoral 20 mg, tid | Drug | Sildenafil - Open label Phase |
Primary outcome
Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 12
Time frame: 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.
7 secondary outcomes
Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 12
Time frame: Baseline and Week 12
Number of Participants With Clinical Worsening
Time frame: Baseline through Week 12
Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12
Time frame: Baseline and Week 12
Change From Baseline in B-Type Natriuretic Peptide (BNP) at Week 12
Time frame: Baseline and Week 12
Change From Baseline in Pro-BNP at Week 12
Time frame: Baseline and Week 12
Change From Baseline in TAPSE Measurement at Week 12
Time frame: Baseline and Week 12
Change From Baseline in BORG Dyspnoea Score at Week 12
Time frame: Baseline and Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28228114Vizza CD, Sastry BK, Safdar Z, Harnisch L, Gao X, Zhang M, Lamba M, Jing ZC. Efficacy of 1, 5, and 20 mg oral sildenafil in the treatment of adults with pulmonary arterial hypertension: a randomized, double-blind study with open-label extension. BMC Pulm Med. 2017 Feb 23;17(1):44. doi: 10.1186/s12890-017-0374-x.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
46 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sildenafil citrate in people with Pulmonary Arterial Hypertension, run by Pfizer's Upjohn has merged with Mylan to form Viatris Inc. at 46 sites in 17 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 46 sites in United States, India, Brazil, Bulgaria, China and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 May 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 12 (time frame: Baseline and Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00430716, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2020.