The Efficacy and Safety of Sildenafil Citrate Used in Combination With Intravenous Epoprostenol in PAH

This study has been completed.

Sponsor:

Information provided by:

Pfizer

ClinicalTrials.gov Identifier:

NCT00159861

First received: September 8, 2005

Last updated: June 7, 2011

Last verified: June 2011

History of Changes

Results First Received: April 2, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver); Primary Purpose: Treatment
Condition:	Pulmonary 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
Subjects were entered into the open-label extension study portion upon completion of the preceding 16-week, placebo controlled core study portion or, for subjects who required a change in epoprostenol dose due to clinical deterioration, after at least 4 weeks in the core study portion.

Reporting Groups

	Description
Placebo: Core Study / Sildenafil: Extension Study	Core Study: Placebo (16 weeks, or at least 4 weeks for subjects who required a change in epoprostenol dose due to clinical deterioration); Extension Study: Sildenafil (until last enrolled subject completed 3 years of treatment) - initial dose 20 mg TID (3 times daily), may have been increased to 40 mg TID or 80 mg TID at discretion of Investigator
Sildenafil: Core Study / Sildenafil: Extension Study	Core Study (16 weeks, or at least 4 weeks for subjects who required a change in epoprostenol dose due to clinical deterioration): Sildenafil 20, 40, or 80 mg TID (3 times daily) based on toleration; Extension Study (until last enrolled subject completed 3 years of treatment): Sildenafil - initial dose 20 mg TID, may have been increased to 40 mg TID or 80 mg TID at discretion of Investigator

Participant Flow for 2 periods

Period 1: Core Study - 16 Weeks

	Placebo: Core Study / Sildenafil: Extension Study	Sildenafil: Core Study / Sildenafil: Extension Study
STARTED	133	134
Treated	131	134
COMPLETED	108 ^[1]	122 ^[2]
NOT COMPLETED	25	12
Death	3	0
Adverse Event	12	6
Lack of Efficacy	2	3
Reason Unspecified	5	3
Subject Defaulted	1	0
Randomized but not Treated	2	0

[1]	Entered A1481153: 115; Did not enter A1481153: 16
[2]	Entered A1481153: 127; Did not enter A1481153: 7

Period 2: Extension Study - up to 3 Years

	Placebo: Core Study / Sildenafil: Extension Study	Sildenafil: Core Study / Sildenafil: Extension Study
STARTED	115 ^[1]	127 ^[1]
Treated	115	127
COMPLETED	53	56
NOT COMPLETED	62	71
Death	24	28
Adverse Event	14	14
Lack of Efficacy	5	1
Reason Unspecified	12	19
Withdrawal by Subject	7	9

[1]	Subjects may have entered extension study after 4 weeks in core study (prior to completion).

Baseline Characteristics

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Reporting Groups

	Description
Placebo/Sildenafil	Core Study: Placebo; Extension Study: Sildenafil - initial dose 20 mg TID (3 times daily), may have been increased to 40 mg TID or 80 mg TID at discretion of Investigator
Sildenafil/Sildenafil	Study A1481141: Sildenafil 20, 40, or 80 mg TID (3 times daily) based on toleration; Extension Study A1481153: Sildenafil - initial dose 20 mg TID, may have been increased to 40 mg TID or 80 mg TID at discretion of Investigator
Total	Total of all reporting groups

Baseline Measures

	Placebo/Sildenafil	Sildenafil/Sildenafil	Total
Number of Participants [units: participants]	131	134	265
Age, Customized [units: participants]
18 to 44 years	47	54	101
45 to 64 years	73	64	137
>= 65 years	11	16	27
Gender [units: participants]
Female	102	110	212
Male	29	24	53

Outcome Measures

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1. Primary:

Categorized Change From Baseline in 6-Minute Walking Distance [ Time Frame: 1 Year, 2 Year, 3 Year ]

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2. Secondary:

Survival Status [ Time Frame: 1, 2, 3, 4, and 5 years ]

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3. Secondary:

Change in Pulmonary Hypertension Criteria for Functional Capacity and Therapeutic Class [ Time Frame: 1 Year, 2 Year, 3 Year ]

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Measure Type	Secondary
Measure Title	Change in Pulmonary Hypertension Criteria for Functional Capacity and Therapeutic Class
Measure Description	Pulmonary hypertension (PH) criteria: Class I: PH without limitation of physical activity (PA) (no undue dyspnea, fatigue, chest pain, near syncope); Class II: PH with slight limitation in PA, comfortable at rest, ordinary PA causes undue dyspnea, fatigue, chest pain, near syncope; Class III: PH with marked limitation in PA, comfortable at rest, less than ordinary activity causes undue dyspnea, fatigue, chest pain or syncope; Class IV: PH with inability to carry out PA without symptoms, signs of right heart failure, dyspnea or fatigue may be present at rest, discomfort increased by any PA.
Time Frame	1 Year, 2 Year, 3 Year
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS; N=number of subjects with evaluable data at core study Baseline. Treatment groups shown by core study randomization; includes subjects in core study and in extension study. Scores for categorized changes for missing visits imputed as worse score of its non-missing neighbors; missing visits with no subsequent score: score coded to missing.

Reporting Groups

	Description
Placebo/Sildenafil	Core Study: Placebo; Extension Study: Sildenafil - initial dose 20 mg TID (3 times daily), may have been increased to 40 mg TID or 80 mg TID at discretion of Investigator
Sildenafil/Sildenafil	Core Study: Sildenafil 20, 40, or 80 mg TID (3 times daily) based on toleration; Extension Study: Sildenafil - initial dose 20 mg TID, may have been increased to 40 mg TID or 80 mg TID at discretion of Investigator

Measured Values

	Placebo/Sildenafil	Sildenafil/Sildenafil
Number of Participants Analyzed [units: participants]	131	134
Change in Pulmonary Hypertension Criteria for Functional Capacity and Therapeutic Class [units: participants]
1 Year: Improved 2 Classes	2	3
1 Year: Improved 1 Class	27	46
1 Year: No Change	59	57
1 Year: Worsened 1 Class	7	3
1 Year: Worsened 2 Classes	0	1
1 Year: Discontinued	22	14
1 Year: Died	14	10
2 Year: Improved 2 Classes	1	4
2 Year: Improved 1 Class	24	31
2 Year: No Change	50	47
2 Year: Worsened 1 Class	7	5
2 Year: Worsened 2 Classes	0	0
2 Year: Discontinued	25	23
2 Year: Died	24	24
3 Year: Improved 2 Classes	1	4
3 Year: Improved 1 Class	21	21
3 Year: No Change	39	37
3 Year: Worsened 1 Class	3	6
3 Year: Worsened 2 Classes	1	0
3 Year: Discontinued	35	33
3 Year: Died	31	33

No statistical analysis provided for Change in Pulmonary Hypertension Criteria for Functional Capacity and Therapeutic Class

4. Secondary:

Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36) [ Time Frame: Baseline, Month 15, Month 27, Month 39 ]

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5. Secondary:

Change From Baseline in European Quality of Life Scale (EuroQol) 5-Dimensions (EQ-5D): Utility Index Score [ Time Frame: Baseline, Month 15, Month 27, Month 39 ]

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6. Secondary:

Change From Baseline in European Quality of Life (EuroQol) Visual Analogue Scale (EQ-5D VAS): Current Health State Score [ Time Frame: Baseline, Month 15, Month 27, Month 39 ]

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7. Secondary:

Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36): Reported Health Transition Score [ Time Frame: Baseline, Month 15, Month 27, Month 39 ]

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8. Secondary:

Change From Baseline in BORG Dyspnea Score [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Month 9, Month 12, Month 15, Month 18, Month 21, Month 24, Month 27, Month 30, Month 33, Month 36 ]

Show Outcome Measure 8

9. Other Pre-specified:

Change in Epoprostenol Dose From Baseline Maintained for 6 Months [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Month 9, and at 3-month intervals through Month 69 ]

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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: No text entered.

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
No text entered.

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, Pfizer, Inc.
ClinicalTrials.gov Identifier:	NCT00159861 History of Changes
Obsolete Identifiers:	NCT00147641
Other Study ID Numbers:	A1481141
Study First Received:	September 8, 2005
Results First Received:	April 2, 2010
Last Updated:	June 7, 2011
Health Authority:	United States: Food and Drug Administration

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