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Trial record 15 of 30 for:    Guatemala | Dominican Republic

Sitaxsentan Efficacy And Safety Trial With A Randomized Prospective Assessment Of Adding Sildenafil (SR-PAAS)

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ClinicalTrials.gov Identifier: NCT00795639
Recruitment Status : Terminated (Safety Issue: The trial was prematurely terminated on Dec 9, 2010, due to safety concerns, specifically new emerging evidence of hepatic injury.)
First Posted : November 21, 2008
Results First Posted : March 1, 2012
Last Update Posted : March 24, 2015
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Pulmonary Arterial Hypertension
Pulmonary Hypertension
Interventions Drug: Sitaxsentan
Drug: Placebo
Enrollment 183

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Sitaxsentan Placebo
Hide Arm/Group Description Sitaxsentan 100 milligrams (mg) tablet orally once a day Matching placebo tablet once a day
Period Title: Overall Study
Started 91 92
Randomized and Not Treated 0 1
Completed 70 66
Not Completed 21 26
Reason Not Completed
Death             1             6
Withdrawal by Subject             1             3
Pregnancy             1             0
Adverse Event             5             2
Other             0             2
Terminated by sponsor             13             12
Randomized and not treated             0             1
Arm/Group Title Sitaxsentan Placebo Total
Hide Arm/Group Description Sitaxsentan 100 milligrams (mg) tablet orally once a day Matching placebo tablet once a day Total of all reporting groups
Overall Number of Baseline Participants 91 91 182
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 91 participants 91 participants 182 participants
less than 18 years 0 3 3
18 to 44 years 53 53 106
45 to 64 years 30 26 56
greater than or equal to 65 years 8 9 17
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 91 participants 91 participants 182 participants
Female
71
  78.0%
68
  74.7%
139
  76.4%
Male
20
  22.0%
23
  25.3%
43
  23.6%
World Health Organization (WHO) Functional Class   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 91 participants 91 participants 182 participants
Functional Class I 0 0 0
Functional Class II 2 0 2
Functional Class III 88 87 175
Functional Class IV 0 0 0
Functional Class Unknown 1 4 5
[1]
Measure Description: WHO Pulmonary Arterial Hypertension (PAH) Functional Classification: I (no limitation on physical activity), II (slight limitation on ordinary physical activity), III (marked limitations on physical activity comfortable at rest) and IV (unable to carry out any physical activity without symptoms, dyspnea and fatigue present at rest).
1.Primary Outcome
Title Change From Baseline in Total Distance Walked During 6 Minute Walk Distance (6MWD) at Week 12
Hide Description 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 is Week 12 results minus baseline results.
Time Frame Baseline/Day 1 and Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population (ITT): all participants who were randomized; missing value at Week 12 imputed with last non-missing value, including the non-missing value obtained at early termination based on last observation carried forward (LOCF)
Arm/Group Title Sitaxsentan Placebo
Hide Arm/Group Description:
Sitaxsentan 100 milligrams (mg) tablet orally once a day
Matching placebo tablet once a day
Overall Number of Participants Analyzed 91 92
Median (Full Range)
Unit of Measure: Meters (m)
Baseline
343.0
(160 to 442)
330.5
(169 to 456)
Change at Week 12
13.0
(-349 to 105)
3.0
(-338 to 104)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sitaxsentan, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0104
Comments Significance test performed using non-parametric analysis of covariance controlling for Baseline 6MWD and PAH etiology and PAH not secondary to a connective tissue disease (other).
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 14
Confidence Interval (2-Sided) 95%
3 to 26
Estimation Comments Missing value at Week 12 assigned as zero if the subject had a predefined clinical worsening event, otherwise, missing value at Week 12 imputed with the last non-missing 6MWD based on LOCF.
2.Secondary Outcome
Title Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Classification at Weeks 4, 8 and 12
Hide Description WHO functional classification for PAH ranges from Class I (no limitation in physical activity, no dyspnea with normal activity) to Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). Improvement = reduction in functional class, deterioration = increase in functional class, no change = no change in functional class.
Time Frame Baseline, Weeks 4, 8 and 12 or Early Termination (ET)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT; N=number of participants with analyzable data; n=number of participants with analyzable data at the specific time point
Arm/Group Title Sitaxsentan Placebo
Hide Arm/Group Description:
Sitaxsentan 100 milligrams (mg) tablet orally once a day
Matching placebo tablet once a day
Overall Number of Participants Analyzed 90 87
Measure Type: Number
Unit of Measure: participants
Week 4 - Improvement (n=90, 87) 6 2
Week 4 - No Change (n=90, 87) 83 84
Week 4 - Deterioration (n=90, 87) 1 1
Week 8 - Improvement (n=86, 81) 13 6
Week 8 - No Change (n=86, 81) 72 73
Week 8 - Deterioration (n=86, 81) 1 2
Week 12 - Improvement (n=80, 72) 17 7
Week 12 - No Change (n=80, 72) 63 64
Week 12 - Deterioration (n=80, 72) 0 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sitaxsentan, Placebo
Comments Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2908
Comments Significance tests of WHO Functional Class performed using the Cochran-Mantel-Haenszel (CMH) test, stratified by Baseline 6MWD (less than 310 meters and greater than or equal to 310 meters) and PAH Etiology (Connective Tissue Disease and others).
Method Cochran-Mantel-Haenszel
Comments The CMH test used modified ridit scores, and the p-value corresponding to ANCOVA (row mean scores) statistics were used.
3.Secondary Outcome
Title Time to Clinical Worsening (TTCW)
Hide Description TTCW defined as the number of days between first dose of study drug and the occurrence of a predefined clinical worsening event. Predefined clinical worsening events included: hospitalization for worsening PAH, on-study death, heart-lung or lung transplant, atrial septostomy or withdrawal due to the addition of any chronic medications for the treatment of worsening PAH.
Time Frame Baseline, Weeks 4, 8 and 12 or ET
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT; N=number of participants with analyzable data
Arm/Group Title Sitaxsentan Placebo
Hide Arm/Group Description:
Sitaxsentan 100 milligrams (mg) tablet orally once a day
Matching placebo tablet once a day
Overall Number of Participants Analyzed 91 91
Median (Full Range)
Unit of Measure: days
NA [1] 
(12 to 86)
NA [2] 
(3 to 73)
[1]
Not Applicable (NA). TTCW not calculated unless at least 50 percent of participants in each treatment group had a clinical worsening event.
[2]
TTCW not calculated unless at least 50 percent of participants in each treatment group had a clinical worsening event.
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Sitaxsentan Placebo
Hide Arm/Group Description Sitaxsentan 100 milligrams (mg) tablet orally once a day Matching placebo tablet once a day
All-Cause Mortality
Sitaxsentan Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Sitaxsentan Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   9/91 (9.89%)   12/91 (13.19%) 
Blood and lymphatic system disorders     
Anaemia * 1  1/91 (1.10%)  0/91 (0.00%) 
Cardiac disorders     
Acute myocardial infarction * 1  0/91 (0.00%)  1/91 (1.10%) 
Acute right ventricular failure * 1  0/91 (0.00%)  1/91 (1.10%) 
Arrhythmia * 1  0/91 (0.00%)  1/91 (1.10%) 
Cardiac failure * 1  1/91 (1.10%)  2/91 (2.20%) 
Cardiac failure congestive * 1  1/91 (1.10%)  0/91 (0.00%) 
Right ventricular failure * 1  1/91 (1.10%)  1/91 (1.10%) 
Gastrointestinal disorders     
Upper gastrointestinal haemorrhage * 1  1/91 (1.10%)  0/91 (0.00%) 
General disorders     
Chest discomfort * 1  0/91 (0.00%)  1/91 (1.10%) 
Fatigue * 1  0/91 (0.00%)  1/91 (1.10%) 
Sudden cardiac death * 1  2/91 (2.20%)  0/91 (0.00%) 
Hepatobiliary disorders     
Hepatic failure * 1  0/91 (0.00%)  1/91 (1.10%) 
Hepatitis * 1  0/91 (0.00%)  1/91 (1.10%) 
Infections and infestations     
Respiratory tract infection * 1  0/91 (0.00%)  1/91 (1.10%) 
Sepsis * 1  0/91 (0.00%)  1/91 (1.10%) 
Injury, poisoning and procedural complications     
Ankle fracture * 1  0/91 (0.00%)  1/91 (1.10%) 
Investigations     
Alanine aminotransferase increased * 1  2/91 (2.20%)  0/91 (0.00%) 
Aspartate aminotransferase increased * 1  2/91 (2.20%)  0/91 (0.00%) 
Blood bilirubin increased * 1  1/91 (1.10%)  0/91 (0.00%) 
International normalised ratio increased * 1  1/91 (1.10%)  0/91 (0.00%) 
Liver function test abnormal * 1  1/91 (1.10%)  0/91 (0.00%) 
Psychiatric disorders     
Decreased activity * 1  1/91 (1.10%)  0/91 (0.00%) 
Renal and urinary disorders     
Nephritis * 1  0/91 (0.00%)  1/91 (1.10%) 
Renal failure * 1  0/91 (0.00%)  1/91 (1.10%) 
Reproductive system and breast disorders     
Cervix haemorrhage uterine * 1  0/91 (0.00%)  1/91 (1.10%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  1/91 (1.10%)  1/91 (1.10%) 
Pulmonary embolism * 1  0/91 (0.00%)  1/91 (1.10%) 
Vascular disorders     
Deep vein thrombosis * 1  0/91 (0.00%)  1/91 (1.10%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA v14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Sitaxsentan Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   23/91 (25.27%)   24/91 (26.37%) 
Gastrointestinal disorders     
Vomiting * 1  2/91 (2.20%)  5/91 (5.49%) 
General disorders     
Chest pain * 1  2/91 (2.20%)  3/91 (3.30%) 
Fatigue * 1  1/91 (1.10%)  4/91 (4.40%) 
Oedema * 1  3/91 (3.30%)  2/91 (2.20%) 
Oedema peripheral * 1  5/91 (5.49%)  8/91 (8.79%) 
Investigations     
Alanine aminotransferase increased * 1  4/91 (4.40%)  1/91 (1.10%) 
Aspartate aminotransferase increased * 1  5/91 (5.49%)  2/91 (2.20%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  1/91 (1.10%)  4/91 (4.40%) 
Hypokalaemia * 1  3/91 (3.30%)  0/91 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  4/91 (4.40%)  1/91 (1.10%) 
Pain in extremity * 1  1/91 (1.10%)  4/91 (4.40%) 
Nervous system disorders     
Dizziness * 1  5/91 (5.49%)  2/91 (2.20%) 
Headache * 1  3/91 (3.30%)  2/91 (2.20%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  1/91 (1.10%)  3/91 (3.30%) 
Dyspnoea * 1  3/91 (3.30%)  7/91 (7.69%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA v14.0
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.
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.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00795639     History of Changes
Other Study ID Numbers: B1321001
First Submitted: November 20, 2008
First Posted: November 21, 2008
Results First Submitted: January 30, 2012
Results First Posted: March 1, 2012
Last Update Posted: March 24, 2015