Back to resultsA Study of the Effectiveness of Sitaxsentan Sodium in Patients With Diastolic Heart Failure
Primary Purpose
Diastolic Heart Failure
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Sitexsentin sodium
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Diastolic Heart Failure
Eligibility Criteria
Inclusion Criteria: 18 or older with chronic heart failure and evidence of diastolic dysfunction on echocardiogram, heart imaging, and a minimum exercise tolerance average time of 120 seconds on two treadmill tests within 2 weeks of enrollment Exclusion Criteria: unstable cardiovascular disease within 4 weeks of screening, history of heart attack, cardiac by-pass surgery or percutaneous intervention, stent placement, within 3 months of screening or amyloidosis, hypertrophic obstructive or restrictive cardiomyopathy, or constrictive pericarditis
Sites / Locations
- University of Alabama at Birmingham
- Mobile Heart Specialists, PC
- Preventative and Research Cardiloogy Providence Hospital
- Central Arkansas Veterans HCS
- Arizona Pulmonary Specialists, LTD
- Parkview Research Center
- Southwest Heart
- University of Arkansas for Medical Services/Cardiology Department
- University of Southern California Medical Center
- Orange County Heart Institute and Research Center
- Sacramento Heart & Vascular Medical Associates
- University of California
- Yale University School of Medicine, Cardiovascular Medicine
- Capital City Research, CCRW
- Florida Heart Group Pa
- The University of Chicago
- Methodist Medical Center
- Cardiovascular Consultants of Maine
- Massachusetts General Hospital Pulmonary and Critical Care Unit
- Brigham and Women's Hospital
- VA Med Ctr Minneapolis
- St. Louis University Hospital
- Washington Univ. School of Medicine
- Nebraska Heart Institute
- Catholic Medical Center d/b/a New England Heart Institute
- Newark Beth Israel Medical Center
- Buffalo Cardipul Assoc
- Columbia University Medical Center, New York Presbyterian Hospital
- Capital Cardiology Associates
- Mid Carolina Cardiology
- Mid Carolina Cardiology
- Wake Forest University Health Sciences
- The Ohio State University
- Oklahoma Foundation for Cardiovascular Research
- The Oregon Clinic
- University of Pennsylvania
- Advanced Heart Failure & Transplant Center
- Albert Einstein Medical Center
- Allegheny General Hospital
- RHJ VA Medical Center
- Black Hills Clinical Research Center
- Stern Cardiovascular Center
- Baylor College of Medicine Pulmonary Section
- Kelsey Seybold Clinic
- Methodist DeBakey Heart Center
- Intermountain Medical Center (a.k.a. LDS Hospital)
- University of Utah
- Fletcher Allen Health Care
- Medical College of Virginia
- University of Wisconsin Hospital & Clinics
- St Michael's Hospital
- SMBD Jewish General Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Sitaxsentan sodium
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Change From Baseline in Treadmill Exercise Time at Maintenance Phase Week 24
Treadmill exercise test is used to assess the functional capacity of participants with cardiac disease. Treadmill exercise test was conducted using the 2 minute incremental Naughton protocol. The Naughton protocol starts with a 2 minute warm-up. The speed of treadmill is set to 1 mile per hour (mph) and the incline is set to 0. After the warm-up, the speed is set at 2 mph for the remainder of the test. The test consists of six, 2 minute intervals. The grade starts at 0 for the first interval, and increases by 3.5 percent every 2 minutes. The change in total exercise time (in seconds) during the treadmill test was reported.
Secondary Outcome Measures
Change From Baseline in Ratio of Transmitral Inflow Velocity (E) to Early Diastolic Velocity of the Mitral Annulus (E') at Maintenance Phase Week 24
Ratio of E to E' is used as a predictor of first cardiac events. Ratio of E to E' was measured using imaging techniques based on Doppler principles. Transmitral inflow velocity was measured by Doppler echocardiography (ECHO) and the early diastolic velocity of the mitral annulus was measured by tissue Doppler imaging (TDI).
Change From Baseline in Left Ventricular Mass at Maintenance Phase Week 24
Left ventricular mass was used as a parameter for the assessment of cardiac function. An increase in left ventricular mass leads to ventricular hypertrophy which is a prognostic factor of cardiovascular morbidity and mortality. Left ventricular mass was measured by ECHO, which was calculated as (1.04 * [{left ventricular end diastolic diameter (LVEDD) + septal diastolic thickness + post wall diastolic thickness}^3 - LVEDD^3]) * 0.8 + 0.6. Left ventricular mass was assessed for the two ECHO modes: parasternal long-axis two dimensional (PLAX 2D) mode and parasternal short-axis view motion (PSAX M) mode.
Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Total Score at Maintenance Phase Week 24
The MLHF is a 21-item questionnaire which used to evaluate QoL in participants suffering from heart failure. The participants were asked to evaluate how their heart condition affected their life during the past month. Each of the 21 items were assessed on a 6-point scale, where 0 = no affect and 5 = very much affected. The MLHF QoL total score was calculated as the sum of the 21 individual QoL questions. The MLHF QoL total score ranged from 0 to 105, where higher scores indicated worse health condition.
Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Physical Score at Maintenance Phase Week 24
The MLHF is a 21-item questionnaire which is used to evaluate QoL in participants suffering from heart failure. The participants were asked to evaluate how their heart condition affected their life during the past month. Each of the 21 items were assessed on a 6-point scale, where 0 = no affect and 5 = very much affected. The MLHF QoL physical score was calculated as the sum of the 8 physical domain QoL questions. The MLHF QoL physical score ranged from 0 to 40, where higher scores indicated worse health condition.
Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Emotional Score at Maintenance Phase Week 24
The MLHF is a 21-item questionnaire which is used to evaluate QoL in participants suffering from heart failure. The participants were asked to evaluate how their heart condition affected their life during the past month. Each of the 21 items were assessed on a 6-point scale, where 0 = no affect and 5 = very much affected. The MLHF QoL emotional score was calculated as the sum of the 5 emotional domain QoL questions. The MLHF QoL emotional score ranged from 0 to 25, where higher scores indicated worse health condition.
Number of Participants With Change From Baseline in New York Heart Association (NYHA) Functional Class at Maintenance Phase Week 24
Participants were classified by NYHA functional class. NYHA class I: participants with cardiac disease but without resulting limitations of physical activity, NYHA class II: participants with cardiac disease resulting in slight limitation of physical activity, NYHA class III: participants with cardiac disease resulting in marked limitation of physical activity, NYHA class IV: participants with cardiac disease resulting in inability to carry on any physical activity without discomfort. Baseline was reported by NYHA functional class and the change from baseline in the functional class was reported as improvement (positive change from baseline), no change and deterioration (negative change from baseline).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00303498
Brief Title
A Study of the Effectiveness of Sitaxsentan Sodium in Patients With Diastolic Heart Failure
Official Title
A PHASE 2 RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED EXPLORATORY EFFICACY STUDY OF SITAXSENTAN SODIUM TO IMPROVE IMPAIRED EXERCISE TOLERANCE IN SUBJECTS WITH DIASTOLIC HEART FAILURE
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
March 27, 2006 (Actual)
Primary Completion Date
May 1, 2008 (Actual)
Study Completion Date
May 1, 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The aim of this study was to determine whether long-term (≥ 6 months at the target dose) blockade of ETA receptors using sitaxsentan showed functional benefit in subjects with chronic Heart Failure and an Left Ventricular Ejection Fraction ≥50%.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diastolic Heart Failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
200 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sitaxsentan sodium
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Sitexsentin sodium
Intervention Description
sitaxsentan 100 mg (target dose) 0rally once daily. A 10-week Run-In Phase was conducted where dosing commenced at 25 mg daily for 2 weeks, and then was stepped up to 50 mg daily for 2 weeks, to 75 mg daily for 2 weeks and then to 100 mg daily for 2 weeks, with an additional 2-week stabilization period (10 weeks total) to a target study dose of 100 mg daily. During the Run-In Phase, if a subject was not able to tolerate upward dose titration to the target dose of 100 mg, the investigator may have elected to continue at the current dosage or reduce the dosage of sitaxsentan or placebo to the subject's immediate prior dose. During the Maintenance Phase, subjects received the highest titrated dose reached of study drug and continued it through the last day of Week M24 of the Maintenance Phase (14 weeks)- total study drug treatment duration= 6 months
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo identical to the study drug in description, dose and duration
Primary Outcome Measure Information:
Title
Change From Baseline in Treadmill Exercise Time at Maintenance Phase Week 24
Description
Treadmill exercise test is used to assess the functional capacity of participants with cardiac disease. Treadmill exercise test was conducted using the 2 minute incremental Naughton protocol. The Naughton protocol starts with a 2 minute warm-up. The speed of treadmill is set to 1 mile per hour (mph) and the incline is set to 0. After the warm-up, the speed is set at 2 mph for the remainder of the test. The test consists of six, 2 minute intervals. The grade starts at 0 for the first interval, and increases by 3.5 percent every 2 minutes. The change in total exercise time (in seconds) during the treadmill test was reported.
Time Frame
Baseline, Week 24 (Maintenance Phase)
Secondary Outcome Measure Information:
Title
Change From Baseline in Ratio of Transmitral Inflow Velocity (E) to Early Diastolic Velocity of the Mitral Annulus (E') at Maintenance Phase Week 24
Description
Ratio of E to E' is used as a predictor of first cardiac events. Ratio of E to E' was measured using imaging techniques based on Doppler principles. Transmitral inflow velocity was measured by Doppler echocardiography (ECHO) and the early diastolic velocity of the mitral annulus was measured by tissue Doppler imaging (TDI).
Time Frame
Baseline, Week 24 (Maintenance Phase)
Title
Change From Baseline in Left Ventricular Mass at Maintenance Phase Week 24
Description
Left ventricular mass was used as a parameter for the assessment of cardiac function. An increase in left ventricular mass leads to ventricular hypertrophy which is a prognostic factor of cardiovascular morbidity and mortality. Left ventricular mass was measured by ECHO, which was calculated as (1.04 * [{left ventricular end diastolic diameter (LVEDD) + septal diastolic thickness + post wall diastolic thickness}^3 - LVEDD^3]) * 0.8 + 0.6. Left ventricular mass was assessed for the two ECHO modes: parasternal long-axis two dimensional (PLAX 2D) mode and parasternal short-axis view motion (PSAX M) mode.
Time Frame
Baseline, Week 24 (Maintenance Phase)
Title
Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Total Score at Maintenance Phase Week 24
Description
The MLHF is a 21-item questionnaire which used to evaluate QoL in participants suffering from heart failure. The participants were asked to evaluate how their heart condition affected their life during the past month. Each of the 21 items were assessed on a 6-point scale, where 0 = no affect and 5 = very much affected. The MLHF QoL total score was calculated as the sum of the 21 individual QoL questions. The MLHF QoL total score ranged from 0 to 105, where higher scores indicated worse health condition.
Time Frame
Baseline, Week 24 (Maintenance Phase)
Title
Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Physical Score at Maintenance Phase Week 24
Description
The MLHF is a 21-item questionnaire which is used to evaluate QoL in participants suffering from heart failure. The participants were asked to evaluate how their heart condition affected their life during the past month. Each of the 21 items were assessed on a 6-point scale, where 0 = no affect and 5 = very much affected. The MLHF QoL physical score was calculated as the sum of the 8 physical domain QoL questions. The MLHF QoL physical score ranged from 0 to 40, where higher scores indicated worse health condition.
Time Frame
Baseline, Week 24 (Maintenance Phase)
Title
Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Emotional Score at Maintenance Phase Week 24
Description
The MLHF is a 21-item questionnaire which is used to evaluate QoL in participants suffering from heart failure. The participants were asked to evaluate how their heart condition affected their life during the past month. Each of the 21 items were assessed on a 6-point scale, where 0 = no affect and 5 = very much affected. The MLHF QoL emotional score was calculated as the sum of the 5 emotional domain QoL questions. The MLHF QoL emotional score ranged from 0 to 25, where higher scores indicated worse health condition.
Time Frame
Baseline, Week M24 (Maintenance Phase)
Title
Number of Participants With Change From Baseline in New York Heart Association (NYHA) Functional Class at Maintenance Phase Week 24
Description
Participants were classified by NYHA functional class. NYHA class I: participants with cardiac disease but without resulting limitations of physical activity, NYHA class II: participants with cardiac disease resulting in slight limitation of physical activity, NYHA class III: participants with cardiac disease resulting in marked limitation of physical activity, NYHA class IV: participants with cardiac disease resulting in inability to carry on any physical activity without discomfort. Baseline was reported by NYHA functional class and the change from baseline in the functional class was reported as improvement (positive change from baseline), no change and deterioration (negative change from baseline).
Time Frame
Baseline, Week 24 (Maintenance Phase)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
18 or older with chronic heart failure and evidence of diastolic dysfunction on echocardiogram, heart imaging, and a minimum exercise tolerance average time of 120 seconds on two treadmill tests within 2 weeks of enrollment
Exclusion Criteria:
unstable cardiovascular disease within 4 weeks of screening, history of heart attack, cardiac by-pass surgery or percutaneous intervention, stent placement, within 3 months of screening or amyloidosis, hypertrophic obstructive or restrictive cardiomyopathy, or constrictive pericarditis
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Mobile Heart Specialists, PC
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36608
Country
United States
Facility Name
Preventative and Research Cardiloogy Providence Hospital
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36608
Country
United States
Facility Name
Central Arkansas Veterans HCS
City
Little Rock
State/Province
Alaska
ZIP/Postal Code
72205
Country
United States
Facility Name
Arizona Pulmonary Specialists, LTD
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
Parkview Research Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85715
Country
United States
Facility Name
Southwest Heart
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85715
Country
United States
Facility Name
University of Arkansas for Medical Services/Cardiology Department
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
University of Southern California Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Orange County Heart Institute and Research Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Sacramento Heart & Vascular Medical Associates
City
Sacramento
State/Province
California
ZIP/Postal Code
95825
Country
United States
Facility Name
University of California
City
San Diego
State/Province
California
ZIP/Postal Code
92103-8411
Country
United States
Facility Name
Yale University School of Medicine, Cardiovascular Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Capital City Research, CCRW
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20011
Country
United States
Facility Name
Florida Heart Group Pa
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
The University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Methodist Medical Center
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61606
Country
United States
Facility Name
Cardiovascular Consultants of Maine
City
Auburn
State/Province
Maine
ZIP/Postal Code
04210
Country
United States
Facility Name
Massachusetts General Hospital Pulmonary and Critical Care Unit
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
VA Med Ctr Minneapolis
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55417-2309
Country
United States
Facility Name
St. Louis University Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Washington Univ. School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Nebraska Heart Institute
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68526
Country
United States
Facility Name
Catholic Medical Center d/b/a New England Heart Institute
City
Manchester
State/Province
New Hampshire
ZIP/Postal Code
03102
Country
United States
Facility Name
Newark Beth Israel Medical Center
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07112
Country
United States
Facility Name
Buffalo Cardipul Assoc
City
Buffalo
State/Province
New York
ZIP/Postal Code
14221-5838
Country
United States
Facility Name
Columbia University Medical Center, New York Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Capital Cardiology Associates
City
Troy
State/Province
New York
ZIP/Postal Code
112180
Country
United States
Facility Name
Mid Carolina Cardiology
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204-3288
Country
United States
Facility Name
Mid Carolina Cardiology
City
Huntersville
State/Province
North Carolina
ZIP/Postal Code
28078
Country
United States
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157-1045
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210-1252
Country
United States
Facility Name
Oklahoma Foundation for Cardiovascular Research
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73120
Country
United States
Facility Name
The Oregon Clinic
City
Portland
State/Province
Oregon
ZIP/Postal Code
97220
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Advanced Heart Failure & Transplant Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
Albert Einstein Medical Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19141
Country
United States
Facility Name
Allegheny General Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15212
Country
United States
Facility Name
RHJ VA Medical Center
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29401
Country
United States
Facility Name
Black Hills Clinical Research Center
City
Rapid City
State/Province
South Dakota
ZIP/Postal Code
57701
Country
United States
Facility Name
Stern Cardiovascular Center
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Baylor College of Medicine Pulmonary Section
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Kelsey Seybold Clinic
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Methodist DeBakey Heart Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Intermountain Medical Center (a.k.a. LDS Hospital)
City
Murray
State/Province
Utah
ZIP/Postal Code
84157
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Fletcher Allen Health Care
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
Facility Name
Medical College of Virginia
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
University of Wisconsin Hospital & Clinics
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
St Michael's Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B1W8
Country
Canada
Facility Name
SMBD Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Citations:
PubMed Identifier
24720918
Citation
Zile MR, Bourge RC, Redfield MM, Zhou D, Baicu CF, Little WC. Randomized, double-blind, placebo-controlled study of sitaxsentan to improve impaired exercise tolerance in patients with heart failure and a preserved ejection fraction. JACC Heart Fail. 2014 Apr;2(2):123-30. doi: 10.1016/j.jchf.2013.12.002. Epub 2014 Feb 26.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1321006&StudyName=A%20study%20of%20the%20effectiveness%20of%20Sitaxsentan%20Sodium%20in%20patients%20with%20Diastolic%20Heart%20Failure
Description
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Learn more about this trial
A Study of the Effectiveness of Sitaxsentan Sodium in Patients With Diastolic Heart Failure
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