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Study Looking at Combination Therapy (Sitaxsentan+Sildenafil) Vs. Monotherapy (Sitaxsentan Alone) SR-PAAS -Sitaxsentan Efficacy And Safety Trial With A Randomized Prospective Assessment Of Adding Sildenafil

This study has been terminated.
(Safety Issue: The trial was prematurely terminated on Dec 9, 2010, due to safety concerns, specifically new emerging evidence of hepatic injury.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00796666
First received: November 20, 2008
Last updated: March 6, 2012
Last verified: May 2011
History of Changes
  Purpose

As monotherapy for pulmonary arterial hypertension (PAH) begins to fail additional therapies are introduced. Although co-administration of sitaxsentan and sildenafil is well tolerated the controlled safety/efficacy database of the combination is limited.


Condition Intervention Phase
Pulmonary Arterial Hypertension
Pulmonary Hypertension
 Drug: Sitaxsentan
Drug: Sitaxsentan and Sildenafil
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Multi-Center, Randomized, Double-Blind, Efficacy And Safety Study Of Monotherapy Sitaxsentan Sodium Versus Combination Therapy With Sitaxsentan Sodium And Sildenafil Citrate In Subjects With Pulmonary Arterial Hypertension Who Have Completed Study B1321001 (NCT00795639)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Time to Clinical Worsening (TTCW) [ Time Frame: Baseline, Weeks 12, 24 or Early Termination (ET) ] [ Designated as safety issue: Yes ]
    Clinical worsening defined as time between first dose of study drug and occurrence of death; or heart-lung/lung transplant; or hospitalization for worsening pulmonary atrial hypertension (PAH); or atrial septostomy; or withdrawal due to addition of chronic medications for treatment of worsening PAH: prostacyclin/prostacyclin analogues/phosphodiesterase-5inhibitors/alternative endothelin receptor antagonists/intravenous inotropes; or increase of calcium channel blockers or oxygen. TTCW measured as duration between study's first dose date in and date when first clinical worsening event occurs.


Secondary Outcome Measures:
  • Change From Baseline in the Total Distance Walked During 6 Minute Walk Distance (6MWD) [ Time Frame: Baseline to Weeks 12 and 24 ] [ Designated as safety issue: Yes ]
    6 MWD 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. Change from baseline = score at Week x - score at baseline.

  • Change From Baseline in World Health Organization (WHO) Functional Class in Participants With PAH at Weeks 12, 24, 48 [ Time Frame: Baseline, Weeks 12, 24 or ET ] [ Designated as safety issue: Yes ]
    WHO PAH Functional Classification of physical activity limitations: I (no limitation), II (slight limitation), III (marked limitations, comfortable at rest) and IV (unable to carry out any physical activity without symptoms). The change from baseline in WHO class was classified as Improved (decrease in functional class), No Change (functional class stayed the same), and Worsened (functional class increased). The change from baseline in WHO functional class at Week X was summarized with frequency count and percentage in each category based on imputed data for missing values at Week X.

  • Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Physical Functioning Domain [ Time Frame: Baseline, Weeks 12, 24 and ET ] [ Designated as safety issue: Yes ]
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Physical Functioning score at Week x minus score at baseline.

  • Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Role Limitations Due to Physical Health Problems Domain [ Time Frame: Baseline, Weeks 12, 24 or ET ] [ Designated as safety issue: Yes ]
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Role Limitations Due to Physical Health Problems score at Week x minus score at baseline.

  • Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Bodily Pain Domain [ Time Frame: Baseline, Weeks 12, 24 or ET ] [ Designated as safety issue: Yes ]
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Bodily Pain score at Week x minus score at baseline.

  • Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - General Health Domain [ Time Frame: Baseline, Weeks 12, 24 or ET ] [ Designated as safety issue: Yes ]
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = General Health score at Week x minus score at baseline.

  • Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Vitality Domain [ Time Frame: Baseline, Weeks 12, 24 or ET ] [ Designated as safety issue: Yes ]
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Vitality score at Week x minus score at baseline.

  • Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Social Functioning Domain [ Time Frame: Baseline, Weeks 12, 24 or ET ] [ Designated as safety issue: Yes ]
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Social Functioning score at Week x minus score at baseline.

  • Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Role Limitation Due to Emotional Problems Domain [ Time Frame: Baseline, Weeks 12, 24 or ET ] [ Designated as safety issue: Yes ]
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Role Limitations Due to Emotional Problems score at Week x minus score at baseline.

  • Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Mental Health Domain [ Time Frame: Baseline, Weeks 12, 24 or ET ] [ Designated as safety issue: Yes ]
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Mental Health score at Week x minus score at baseline.

  • Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Composite Mental Health [ Time Frame: Baseline, Weeks 12, 24 or ET ] [ Designated as safety issue: Yes ]
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Composite Mental Health score at Week x minus score at baseline.

  • Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Composite Physical Health [ Time Frame: Baseline, Weeks 12, 24 or ET ] [ Designated as safety issue: Yes ]
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Composite Physical Health score at Week x minus score at baseline.


Enrollment: 131
Study Start Date: May 2009
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitaxsentan and Placebo
Monotherapy arm
 Drug: Sitaxsentan
Sitaxsentan = 100 mg tablet administered orally, once daily Sildenafil placebo = 1 tablet administered orally, three times a day
Experimental: Sitaxsentan and Sildenafil
Combination treatment
 Drug: Sitaxsentan and Sildenafil
Sitaxsentan = 100 mg tablet administered orally, once daily plus Sildenafil = 20 mg tablet administered orally, three times a day

  Eligibility

Ages Eligible for Study:   16 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Previously enrolled in B1321001 (NCT00795639) and completed the 12-week study as planned.

Exclusion Criteria:

  • Treated with an investigational drug, other than sitaxsentan sodium in B1321001 (NCT00795639), or device that has not received regulatory approval within the 30 days prior to Baseline/Day 1 or during the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00796666

  Show 48 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
To obtain contact information for a study center near you, click here.  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00796666     History of Changes
Other Study ID Numbers: B1321003
Study First Received: November 20, 2008
Results First Received: January 26, 2012
Last Updated: March 6, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
endothelin receptor antagonist (ETRA)
Sitaxsentan

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases
Sildenafil
Vasodilator Agents
 Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 18, 2013