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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00644332
First received: March 24, 2008
Last updated: May 29, 2012
Last verified: May 2012
  Purpose

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 Intervention Phase
Chronic Angina
Drug: Ranolazine
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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).

  • Compare Changes From Baseline (BL) in Other Like Items of the WISQ With the SAQ Following Ranolazine Treatment [ Time Frame: Baseline to 4 Weeks ] [ Designated as safety issue: No ]
    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).

  • Determine the Effect of Ranolazine on Angina Frequency as Measured by Patient-reported Diaries [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
    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.

  • Determine the Effect of Ranolazine on Nitroglycerin Consumption as Measured by Patient-reported Diaries [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
    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.

  • Determine Changes From Baseline in the Duke Activity Status Index (DASI) Following Ranolazine Treatment [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 172
Study Start Date: November 2007
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Ranolazine
    Oral dosage form.
    Other Name: Ranexa
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00644332

  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

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00644332     History of Changes
Other Study ID Numbers: CVT 3041
Study First Received: March 24, 2008
Results First Received: May 29, 2012
Last Updated: May 29, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Angina Pectoris
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Ranolazine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014