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

This study has been terminated.

( This study was terminated at the recommendation of an independent Data Monitoring Committee. The decision was not based on any safety concerns. )

Study NCT00430716 Information provided by Pfizer

First Received on January 31, 2007. Last Updated on May 25, 2011 History of Changes

Results First Received: April 22, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, Investigator); Primary Purpose: Treatment
Condition:	Pulmonary Arterial Hypertension
Intervention:	Drug: Sildenafil citrate

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Sildenafil 1 mg	Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 5 and 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 5 mg	Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 1 and 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 20 mg	Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase).

Participant Flow for 2 periods

Period 1: Double Blind Phase

	Sildenafil 1 mg	Sildenafil 5 mg	Sildenafil 20 mg
STARTED	42	43	45
Treated	41	43	45
COMPLETED	36	38	39
NOT COMPLETED	6	5	6
Death	1	0	0
No longer willing to participate	2	1	1
Unspecified	0	2	0
Study terminated by sponsor	1	1	2
Adverse Event	1	1	3
Not met eligibility criteria	1	0	0

Period 2: Open Label Phase

	Sildenafil 1 mg	Sildenafil 5 mg	Sildenafil 20 mg
STARTED	36	38	39
COMPLETED	27	31	32
NOT COMPLETED	9	7	7
Lost to Follow-up	1	0	1
No longer willing to participate	0	1	1
Unspecified	3	1	1
Protocol Violation	1	0	0
Study terminated by sponsor	4	5	4

Baseline Characteristics

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Reporting Groups

	Description
Sildenafil 1 mg	Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 5 and 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 5 mg	Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 1 and 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
Sildenafil 20 mg	Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase).

Baseline Measures

	Sildenafil 1 mg	Sildenafil 5 mg	Sildenafil 20 mg	Total
Number of Participants [units: participants]	41	43	45	129
Age [units: Years] Mean ± Standard Deviation	42.5 ± 16.5	44.4 ± 17.4	46.4 ± 17.7	44.5 ± 17.2
Gender [units: Participants]
Female	28	33	26	87
Male	13	10	19	42
Six Minute Walk Test (6 MWT) ^[1] [units: Meters] Mean ± Standard Deviation	347.5 ± 67.3	347.7 ± 73.4	340.4 ± 76.3	345.1 ± 71.9
mean pulmonary artery pressure (mPAP) [units: millimeter(mm) of mercury(Hg)] Mean ± Standard Deviation	57.2 ± 21.9	55.4 ± 19.7	51.1 ± 21.4	54.5 ± 21.0
B-type natriuretic peptide (BNP) ^[2] [units: picogram(pg)/milliter(mL)] Mean ± Standard Deviation	272.4 ± 344.7	207.2 ± 220.3	248.9 ± 268.3	242.8 ± 280.4
Pro-BNP ^[3] [units: pg/mL] Mean ± Standard Deviation	1540.8 ± 1853.7	1225.6 ± 1279.3	1153.1 ± 1191.4	1300.8 ± 1458.6
Tricuspid annular plane systolic excursion (TAPSE) ^[4] [units: cm] Mean ± Standard Deviation	1.3 ± 0.6	1.2 ± 0.7	1.4 ± 0.8	1.3 ± 0.7
BORG dyspnoea score ^[5] [units: Units on a scale] Mean ± Standard Deviation	2.9 ± 2.5	3.1 ± 1.9	2.8 ± 2.1	2.9 ± 2.2
World Health Organization (WHO) Classification of PAH ^[6] [units: Participants]
Class I	0	1	3	4
Class II	25	22	27	74
Class III	16	16	13	45
Class IV	0	1	0	1

[1]	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.
[2]	BNP is a non-invasive biomarker and an indicator of progression of pulmonary hypertension (PAH) /right ventricular (RV) dysfunction in participants with PAH.
[3]	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.
[4]	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 / RV dysfunction.
[5]	BORG dyspnoea scale includes score from 0 -10 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.
[6]	PAH criteria for WHO Class: Class I (Participants with no limitation of physical activity); Class II (Participants with slight limitation of physical activity); Class III (Participants with marked limitation of physical activity); Class IV (Participants with inability to carry out any physical activity).

Outcome Measures

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1. Primary:

Change From Baseline in the Total Distance Walked During 6MWT at Week 12 [ Time Frame: Baseline and Week 12 ]

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2. Secondary:

Change From Baseline in mPAP at Week 12 [ Time Frame: Baseline and Week 12 ]

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3. Secondary:

Time to Clinical Worsening [ Time Frame: Baseline through Week 12 ]

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4. Secondary:

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 ]

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5. Secondary:

Change From Baseline in BNP at Week 12 [ Time Frame: Baseline and Week 12 ]

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6. Secondary:

Change From Baseline in Pro-BNP at Week 12 [ Time Frame: Baseline and Week 12 ]

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7. Secondary:

Change From Baseline in TAPSE Measurement at Week 12 [ Time Frame: Baseline and Week 12 ]

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8. Secondary:

Change From Baseline in BORG Dyspnoea Score at Week 12 [ Time Frame: Baseline and Week 12 ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The trial was not designed to demonstrate the equivalence of doses and due to premature study termination, the resulting sample size was not adequately powered to show superiority.

Results Point of Contact:

Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com

No publications provided

Responsible Party:	Director, Clinical Trial Disclosure Group, Pfizer Inc
ClinicalTrials.gov Identifier:	NCT00430716 History of Changes
Other Study ID Numbers:	A1481244
Study First Received:	January 31, 2007
Results First Received:	April 22, 2011
Last Updated:	May 25, 2011
Health Authority:	United States: Food and Drug Administration