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

• ClinicalTrials.gov Identifier: NCT00430716
• Recruitment Status: Terminated
• First Posted: February 2, 2007
• Results First Posted: May 17, 2011
• Last Update Posted: December 22, 2020
• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• Information provided by (Responsible Party): Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )

Tracking Information

• First Submitted Date: January 31, 2007
• First Posted Date: February 2, 2007
• Results First Submitted Date: April 22, 2011
• Results First Posted Date: May 17, 2011
• Last Update Posted Date: December 22, 2020
• Actual Study Start Date: April 8, 2008
• Actual Primary Completion Date: May 25, 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 2, 2020)

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.

• Original Primary Outcome Measures (submitted: January 31, 2007): The change from baseline in the total distance walked during the 6MWT at Week 12 of the study.

Current Secondary Outcome Measures (submitted: October 2, 2020)

• Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 12 [ Time Frame: Baseline and Week 12 ]
  mPAP was measured using a pressure transducer positioned at the mid-axillary line.
• Number of Participants With Clinical Worsening [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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).

Original Secondary Outcome Measures (submitted: January 31, 2007)

• Change from baseline at Week 12 in mean pulmonary artery pressure (mPAP).
• Time from randomization to the first occurrence of clinical worsening defined as death or lung transplantation or hospitalisation due to pulmonary hypertension or initiation of prostacyclin therapy or initiation of bosentan therapy.
• Change from baseline at Week 12 in the pulmonary hypertension criteria for functional capacity and therapeutic class. Change from baseline at Week 12 in BNP and pro-BNP levels.
• Change from baseline at Week 12 in TAPSE measurement.Change from baseline at Week 12 in the BORG dyspnoea score.
• Change in chronic use of background therapy for PAH: The percentage of subjects with one or more additions (from baseline) in the class(es) of drugs used as background medication (i.e. oxygen, diuretics, calcium channel blockers and digoxin).
• AND The percentage of subjects with one or more discontinuations (from baseline) in the class(es) of drugs used as background medication (i.e. oxygen, diuretics, calcium channel blockers and digoxin).
• The change from baseline at Week 12 in the additional haemodynamic parameters such as: cardiac output (CO), PVR, PVRI and mixed venous oxygen saturation (MVO2).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.
• 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)
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Pulmonary Arterial Hypertension

Intervention

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

Study Arms

• Experimental: Sildenafil High dose
  Intervention: Drug: Sildenafil citrate
• Experimental: Sildenafil Low dose
  Intervention: Drug: Sildenafil citrate
• Experimental: Sildenafil medium dose
  Intervention: Drug: Sildenafil citrate
• Experimental: Sildenafil - Open label Phase
  Open label extension from week 12 to week 24.
  Intervention: Drug: Sildenafil citrate

• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 9, 2011): 130
• Original Enrollment (submitted: January 31, 2007): 174
• Actual Study Completion Date: May 25, 2010
• Actual Primary Completion Date: May 25, 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Brazil, Bulgaria, China, Greece, India, Italy, Latvia, Malaysia, Netherlands, Philippines, Poland, Romania, Russian Federation, Thailand, United Kingdom, United States
• Removed Location Countries: Denmark, Panama

Administrative Information

• NCT Number: NCT00430716
• Other Study ID Numbers: A1481244; 2006-006748-76 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )
• Original Responsible Party: Not Provided
• Current Study Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• Original Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: December 2020