A Randomized, Double-Blind, Placebo-Controlled Study of Sildenafil in Children With Pulmonary Arterial Hypertension.

This study has been completed.

Sponsor:

Information provided by:

Pfizer

ClinicalTrials.gov Identifier:

NCT00159913

First received: September 8, 2005

Last updated: September 15, 2009

Last verified: September 2009

History of Changes

Results First Received: June 2, 2009

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

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
The study was conducted at 32 centers in North, Latin and South America, Europe and Asia.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of the 324 subjects screened, 235 subjects were randomized. 234 received treatment. One subject(sildenafil medium dose group) withdrew prior to taking any study treatment as the hemodynamic entrance criteria were not met.

Reporting Groups

	Description
Sildenafil Low Dose	Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights > 20-45 kg and > 45 kg, through Day 112. Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the >= 8-20 kg weight group.
Sildenafil Medium Dose	Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112
Sildenafil High Dose	Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112
Placebo	Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.

Participant Flow: Overall Study

	Sildenafil Low Dose	Sildenafil Medium Dose	Sildenafil High Dose	Placebo
STARTED	42	55	77	60
COMPLETED	40	55	75	58
NOT COMPLETED	2	0	2	2
Adverse Event	1	0	1	0
Withdrawal by Subject	0	0	0	1
Lost to Follow-up	0	0	0	1
Protocol Violation	1	0	1	0

Baseline Characteristics

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Reporting Groups

	Description
Sildenafil Low Dose	Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights > 20-45 kg and > 45 kg, through Day 112. Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the >= 8-20 kg weight group.
Sildenafil Medium Dose	Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112
Sildenafil High Dose	Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112
Placebo	Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.
Total	Total of all reporting groups

Baseline Measures

	Sildenafil Low Dose	Sildenafil Medium Dose	Sildenafil High Dose	Placebo	Total
Number of Participants [units: participants]	42	55	77	60	234
Age, Customized [units: participants]
1-4 Years	0	9	19	7	35
5-12 Years	25	28	36	37	126
13-17 Years	17	18	22	16	73
>= 18 Years	0	0	0	0	0
Gender [units: participants]
Female	25	31	51	38	145
Male	17	24	26	22	89

Outcome Measures

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1. Primary:

Percent Change From Baseline in Peak Volume of Oxygen (VO2) Consumed : Intent To Treat Population [ Time Frame: Baseline, Week 16 ]

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2. Primary:

Percent Change From Baseline in Peak Volume of Oxygen (VO2) Consumed : Per Protocol Population [ Time Frame: Baseline, Week 16 ]

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3. Secondary:

Change From Baseline to Week 16 in Mean Pulmonary Artery Pressure (mPAP) [ Time Frame: Baseline, Week 16 ]

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4. Secondary:

Change From Baseline to Week 16 in Pulmonary Vascular Resistance Index (PVRI) [ Time Frame: Baseline, Week 16 ]

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5. Secondary:

Percent Change From Baseline to Week 16 in: Respiratory Exchange Ratio (RER) [ Time Frame: Baseline, Week 16 ]

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6. Secondary:

Percent Change From Baseline to Week 16 in Time to Maximum Volume of Oxygen Consumed (VO2) [ Time Frame: Baseline, Week 16 ]

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7. Secondary:

Change From Baseline to Week 16 in Pulmonary Vascular Resistance (PVR) [ Time Frame: Baseline, Week 16 ]

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8. Secondary:

Change From Baseline to Week 16 in Cardiac Index (CI) [ Time Frame: Baseline, Week 16 ]

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9. Secondary:

Change From Baseline to Week 16 in Right Atrial Pressure (RAP) [ Time Frame: Baseline, Week 16 ]

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10. Secondary:

Change From Baseline to Week 16 in Child Health Questionnaire Parent Form (CHQ-PF28), Physical Scale [ Time Frame: Baseline, Week 16 ]

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11. Secondary:

Change From Baseline to Week 16 in Child Health Questionnaire Parent Form (CHQ-PF28), Psychosocial Scales [ Time Frame: Baseline, Week 16 ]

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12. Secondary:

Change From Baseline to Week 16 in World Health Organization (WHO) Pulmonary Hypertension (PH) Functional Class [ Time Frame: Baseline, Week 16 ]

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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 < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 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
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.govCallCenter@pfizer.com

No publications provided by Pfizer

Publications automatically indexed to this study:

Cappelleri JC, Hwang LJ, Mardekian J, Mychaskiw MA. Assessment of measurement properties of peak VO(2) in children with pulmonary arterial hypertension. BMC Pulm Med. 2012 Sep 10;12:54. doi: 10.1186/1471-2466-12-54.

Barst RJ, Ivy DD, Gaitan G, Szatmari A, Rudzinski A, Garcia AE, Sastry BK, Pulido T, Layton GR, Serdarevic-Pehar M, Wessel DL. A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial hypertension. Circulation. 2012 Jan 17;125(2):324-34. Epub 2011 Nov 29.

Responsible Party:	Director, Clinical Trial Disclosure Group, Pfizer Inc
ClinicalTrials.gov Identifier:	NCT00159913 History of Changes
Other Study ID Numbers:	A1481131
Study First Received:	September 8, 2005
Results First Received:	June 2, 2009
Last Updated:	September 15, 2009
Health Authority:	United States: Food and Drug Administration

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