A Study of the Effectiveness of Sitaxsentan Sodium in Patients With Diastolic Heart Failure

Diastolic Heart Failure Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00303498
• Other study ID #: B1321006
• Secondary ID: FDHF01
• Status: Completed
• Phase: Phase 2
• Start date: March 27, 2006
• Est. completion date: May 1, 2008

Study information

• Verified date: December 2022
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: May 1, 2008
• Est. primary completion date: May 1, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diastolic Heart Failure
• Heart Failure
• Heart Failure, Diastolic

Intervention

Drug:
• Sitexsentin sodium
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
• Placebo
placebo identical to the study drug in description, dose and duration

Locations

Country	Name	City	State
Canada	SMBD Jewish General Hospital	Montreal	Quebec
Canada	St Michael's Hospital	Toronto	Ontario
United States	Cardiovascular Consultants of Maine	Auburn	Maine
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital Pulmonary and Critical Care Unit	Boston	Massachusetts
United States	Buffalo Cardipul Assoc	Buffalo	New York
United States	Fletcher Allen Health Care	Burlington	Vermont
United States	RHJ VA Medical Center	Charleston	South Carolina
United States	Mid Carolina Cardiology	Charlotte	North Carolina
United States	The University of Chicago	Chicago	Illinois
United States	The Ohio State University	Columbus	Ohio
United States	Stern Cardiovascular Center	Germantown	Tennessee
United States	Baylor College of Medicine Pulmonary Section	Houston	Texas
United States	Kelsey Seybold Clinic	Houston	Texas
United States	Methodist DeBakey Heart Center	Houston	Texas
United States	Mid Carolina Cardiology	Huntersville	North Carolina
United States	Nebraska Heart Institute	Lincoln	Nebraska
United States	Central Arkansas Veterans HCS	Little Rock	Alaska
United States	University of Arkansas for Medical Services/Cardiology Department	Little Rock	Arkansas
United States	University of Southern California Medical Center	Los Angeles	California
United States	University of Wisconsin Hospital & Clinics	Madison	Wisconsin
United States	Catholic Medical Center d/b/a New England Heart Institute	Manchester	New Hampshire
United States	VA Med Ctr Minneapolis	Minneapolis	Minnesota
United States	Mobile Heart Specialists, PC	Mobile	Alabama
United States	Preventative and Research Cardiloogy Providence Hospital	Mobile	Alabama
United States	Intermountain Medical Center (a.k.a. LDS Hospital)	Murray	Utah
United States	Yale University School of Medicine, Cardiovascular Medicine	New Haven	Connecticut
United States	Columbia University Medical Center, New York Presbyterian Hospital	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Oklahoma Foundation for Cardiovascular Research	Oklahoma City	Oklahoma
United States	Orange County Heart Institute and Research Center	Orange	California
United States	Florida Heart Group Pa	Orlando	Florida
United States	Methodist Medical Center	Peoria	Illinois
United States	Advanced Heart Failure & Transplant Center	Philadelphia	Pennsylvania
United States	Albert Einstein Medical Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Arizona Pulmonary Specialists, LTD	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	The Oregon Clinic	Portland	Oregon
United States	Black Hills Clinical Research Center	Rapid City	South Dakota
United States	Medical College of Virginia	Richmond	Virginia
United States	Sacramento Heart & Vascular Medical Associates	Sacramento	California
United States	St. Louis University Hospital	Saint Louis	Missouri
United States	Washington Univ. School of Medicine	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	University of California	San Diego	California
United States	Capital Cardiology Associates	Troy	New York
United States	Parkview Research Center	Tucson	Arizona
United States	Southwest Heart	Tucson	Arizona
United States	Capital City Research, CCRW	Washington	District of Columbia
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, Week 24 (Maintenance Phase)
Secondary	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).	Baseline, Week 24 (Maintenance Phase)
Secondary	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.	Baseline, Week 24 (Maintenance Phase)
Secondary	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.	Baseline, Week 24 (Maintenance Phase)
Secondary	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.	Baseline, Week 24 (Maintenance Phase)
Secondary	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.	Baseline, Week M24 (Maintenance Phase)
Secondary	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).	Baseline, Week 24 (Maintenance Phase)

External Links

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