An Open-label, Multi-center Study Evaluating the Validity, Reliability, and Responsiveness of a New Female-specific Angina Questionnaire in Women With Chronic Angina Treated With Ranolazine Extended-release Tablets (CVT 3041)

Study Description

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Brief Summary:

According to the American Heart Association (AHA) 2011 update of heart disease and stroke statistics, more than 9 million adult patients in the United States (US) have angina. This update also notes that a study of 4 national cross-sectional health examination studies found that, among Americans 40 to 74 years of age, the age-adjusted prevalence of angina was higher among women than men. Per ACC/AHA guidelines, the goal of antianginal therapy is the complete or near complete elimination of anginal chest pain and a return to normal activities and functional capacity. However, evaluating angina and responses to antianginal therapy is often not straightforward. This is particularly true of female patients with angina. Because angina and response to antianginal therapy may differ in men and women, an instrument designed specifically to address symptomatology in women with angina could enhance our understanding and characterization of angina and responses to therapy in this population. The current study will evaluate the validity, reliability, and responsiveness of the newly developed Women's Ischemia Symptom Questionnaire (WISQ) based on changes in angina symptomatology in a female angina population treated with ranolazine, compared with the widely used Seattle Angina Questionnaire (SAQ).

Condition or disease	Intervention/treatment	Phase
Chronic Angina	Drug: Ranolazine	Phase 4

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	172 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Official Title:	An Open-label, Multi-center Study Evaluating the Validity, Reliability, and Responsiveness of a New Women's Ischemia Symptom Questionnaire in Women With Chronic Angina Treated With Ranolazine Extended-release Tablets (CVT 3041)
Study Start Date :	November 2007
Actual Primary Completion Date :	January 2011
Actual Study Completion Date :	January 2011

Arms and Interventions

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Intervention Details:

Drug: Ranolazine
Oral dosage form.
Other Name: Ranexa

Outcome Measures

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Primary Outcome Measures :

1. Evaluate the Validity of the WISQ in Women With Chronic Angina Based on Changes in Patient-reported Angina Frequency and Nitroglycerin (NTG) Consumption Before and Following Treatment With Ranolazine Assessed as Coefficient of Determination (R^2) [ Time Frame: Baseline to Week 4 ]
   Validity of the WISQ was assessed by regression analysis. Results of this analysis are reported as the estimated coefficient of determination (R^2) of the WISQ Total Score at 4 weeks regressed on 4-week angina frequency, 4-week NTG use, and DASI score at 4 weeks. For mean (SEM) Baseline and Week 4 values for angina frequency and NTG use, please refer to Secondary Outcome Measures 7 and 8. For mean (SEM) Baseline and Week 4 DASI values, please refer to Secondary Outcome Measure 9.
2. Evaluate the Reliability of the WISQ in Women With Chronic Angina Based on Changes in Patient-reported Angina Frequency and NTG Consumption Before and Following Treatment With Ranolazine Assessed as Cronbach's Alpha Value [ Time Frame: Baseline to Week 4 ]
   Reliability of the WISQ was assessed by estimating Cronbach's alpha (standardized); values of 0.7 or higher were to be considered adequate. (Standardized Cronbach's alpha is a coefficient of reliability or consistency, and is a function of the average inter-item correlation.) Cronbach's alpha was calculated for the WISQ instrument overall and for the Angina Frequency/Severity and Angina Stability subscales. Missing item responses were not imputed.
3. Evaluate the Responsiveness of the WISQ in Women With Chronic Angina Based on Changes in Patient-reported Angina Frequency and NTG Consumption Before and Following Treatment With Ranolazine Assessed by Regression Analysis [ Time Frame: Baseline to Week 4 ]
   Responsiveness of the WISQ was assessed as the estimated coefficient of determination (R^2) of the change from baseline WISQ Total Score at 4 weeks regressed on change from baseline angina frequency and change from baseline NTG use. For mean (SEM) Baseline and Week 4 values for angina frequency and NTG use, please refer to Secondary Outcome Measures 7 and 8.

Secondary Outcome Measures :

1. Determine Whether the WISQ is Noninferior to the Seattle Angina Questionnaire (SAQ) With Regard to Angina Frequency Items Based on Changes From Baseline (BL) in the Angina Frequency Items of the WISQ With the SAQ Following Ranolazine Treatment [ Time Frame: Baseline to 4 Weeks ]
   Changes from BL in angina frequency items following ranolazine treatment were measured. Analysis: multiple linear regression; response variable: ΔWISQ - ΔSAQ; independent variables: age and BL WISQ and SAQ scores. WISQ items: 15 points (higher=more severe state); SAQ items: 12 points (lower=more severe state). WISQ scores were recalibrated by multiplying by .75. Noninferiority was to be considered demonstrated if the lower limit of a 2-sided 95% CI for WISQ mean - SAQ mean was above the prespecified margin (WISQ vs SAQ difference of -2).
2. Compare Changes From Baseline (BL) in the Physical Limitation Items of the WISQ With the SAQ Following Ranolazine Treatment [ Time Frame: Baseline to 4 Weeks ]
   Changes from BL in stress, excitement, temperature, satiety, anger, and other limitation items following ranolazine treatment were measured. Analysis: multiple linear regression; response variable: ΔWISQ - ΔSAQ; independent variables: age and BL WISQ and SAQ scores. WISQ items: 27 points (higher=more severe state); SAQ items: 45 points (lower=more severe state). WISQ scores were recalibrated by multiplying by 15/27. Noninferiority was to be considered demonstrated if the lower limit of a 2-sided 95% CI for WISQ mean - SAQ mean was above the prespecified margin (WISQ vs SAQ difference of -2).
3. Compare Changes From Baseline (BL) in Other Like Items of the WISQ With the SAQ Following Ranolazine Treatment [ Time Frame: Baseline to 4 Weeks ]
   Changes from BL in stress, excitement, temperature, satiety, anger, and other limitation items following ranolazine treatment were measured. Analysis: multiple linear regression; response variable: ΔWISQ - ΔSAQ; independent variables: age and BL WISQ and SAQ scores. WISQ items: 27 points (higher=more severe state); SAQ items: 45 points (lower=more severe state). WISQ scores were recalibrated by multiplying by 15/27. Noninferiority was to be considered demonstrated if the lower limit of a 2-sided 95% CI for WISQ mean - SAQ mean was above the prespecified margin (WISQ vs SAQ difference of -2).
4. Determine the Effect of Ranolazine on Angina Frequency as Measured by Patient-reported Diaries [ Time Frame: Baseline to Week 4 ]
   Angina episodes were recorded by subjects in their diaries. Weekly frequency of angina episodes was calculated for the two-week baseline period and the last two weeks of the study.
5. Determine the Effect of Ranolazine on Nitroglycerin Consumption as Measured by Patient-reported Diaries [ Time Frame: Baseline to Week 4 ]
   Nitroglycerin use was recorded by subjects in their diaries. Weekly frequency of NTG use was calculated for the two-week baseline period and the last two weeks of the study.
6. Determine Changes From Baseline in the Duke Activity Status Index (DASI) Following Ranolazine Treatment [ Time Frame: Baseline to Week 4 ]
   The DASI was analyzed as mean values at baseline and Week 4. The DASI is a self-administered questionnaire that measures a patient's functional capacity. It can be used to get a rough estimate of a patient's peak oxygen uptake. The maximum score for the DASI is 58.2 (better functional ability/capacity) and the minimum score is 0 (worse functional ability/capacity).
7. Evaluate the Degree of Correlation Between Changes From Baseline in Items of the WISQ and SAQ With Changes From Baseline in Angina Frequency and NTG Diary Data and the DASI [ Time Frame: Baseline to Week 4 ]
   The DASI is a self-administered questionnaire that measures a patient's functional capacity. It can be used to get a rough estimate of a patient's peak oxygen uptake. The maximum score for the DASI is 58.2 (better functional ability/capacity) and the minimum score is 0 (worse functional ability/capacity). The planned analysis was the amount of variation in WISQ and SAQ score changes from baseline explained by changes in angina frequency, NTG use, and DASI score assessed by multiple linear regression analysis.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• At least 3 months of documented history of stable angina or angina equivalents that is relieved by rest and/or sublingual NTG
• Taking antianginal therapy with beta-blockers, and/or dihydropyridine calcium antagonists, and/or long-acting nitrates for at least 4 weeks
• Mean angina frequency of ≥ 2 attacks per week
• Documented clinical evidence of ischemia

Exclusion Criteria:

• Clinically significant hepatic impairment
• Uncontrolled clinically significant cardiac arrhythmias or a history of ventricular fibrillation, torsades de points, or other life-threatening ventricular arrhythmias not associated with acute coronary syndrome
• Treatment with strong cytochrome P450 inhibitors including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, or saquinavir
• Prior treatment with ranolazine
• End-stage renal disease requiring dialysis
• Myocardial infarction or unstable angina

Contacts and Locations

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  Show 29 Study Locations

Sponsors and Collaborators

Gilead Sciences

Investigators

Principal Investigator:	Nanette K. Wenger, MD	Emory University
Principal Investigator:	Noel Bairey Merz, MD	Cedars-Sinai Medical Center

More Information

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Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00644332 History of Changes
Other Study ID Numbers:	CVT 3041
First Posted:	March 26, 2008
Results First Posted:	July 2, 2012
Last Update Posted:	July 2, 2012
Last Verified:	May 2012

Additional relevant MeSH terms:

Angina Pectoris; Chest Pain; Pain; Neurologic Manifestations; Nervous System Diseases; Myocardial Ischemia; Heart Diseases	Cardiovascular Diseases; Vascular Diseases; Signs and Symptoms; Ranolazine; Sodium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action