Evaluation of a Flushing ASsessment Tool (FAST) in Subjects Receiving Niacin Extended-release Plus Aspirin

Phase 3

Completed

• Conditions: Dyslipidemia
• Interventions: Drug: Niacin extended-release (NER); Drug: Niacin extended-release (NER) placebo; Drug: Aspirin (ASA); Drug: Aspirin (ASA) placebo

• Registration Number: NCT00630877
• Lead Sponsor: Abbott

Brief Summary

The primary purpose of this study was to evaluate the psychometric characteristics (reliability, validity, and responsiveness) of a Flushing ASsessment Tool (FAST) in subjects receiving niacin extended-release (NER) plus aspirin (ASA) daily for 6 weeks.

The FAST is a questionnaire that was developed to provide a detailed assessment of flushing symptoms and their impact in patients receiving niacin therapy. The effect of aspirin on flushing symptoms, as measured by the FAST, was also evaluated.

Detailed Description

This study was designed to evaluate the psychometric characteristics of the FAST questionnaire.

The FAST is a self-administered questionnaire, completed using a hand-held electronic data capture device (LogPad e-diary). Subjects recorded the start and stop date and time of each flushing event, the presence and severity of individual flushing symptoms (redness, warmth, tingling and/or itching), and an overall assessment of their flushing experience.

Evaluation of the psychometric characteristics of the FAST was based on 3 primary data analyses: 1 ) test-retest reliability based on the intraclass correlation coefficient; 2) construct validity based on Spearman correlation coefficients; and 3) responsiveness based on changes in FAST scores. The mean and maximum severity of flushing events, as measured by the FAST, were the primary variables evaluated in each of the 3 data analyses mentioned above. Psychometric analyses were performed blinded to treatment group assignment.

Study Timeline

• Study Start: 2008-02
• Study First Submitted: 2008-02-29
• Study First Submitted QC: 2008-02-29
• Study First Posted: 2008-03-07
• Primary Completion: 2008-06
• Study Completion: 2008-06
• Results First Submitted: 2009-06-11
• Status Verified: 2009-09
• Results First Submitted QC: 2009-09-09
• Last Update Submitted: 2009-09-09
• Results First Posted: 2009-10-09
• Last Update Posted: 2009-10-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 276

Inclusion Criteria

• Subject must be 18 years of age or older.
• If female, subject is either not of childbearing potential, defined as postmenopausal for at least one year or surgically sterile, or is of childbearing potential and must agree to practice birth control for the duration of the study.
• Have dyslipidemia as demonstrated by laboratory results.

Exclusion Criteria

• Have glycosylated hemoglobin (HbA1c) >= 9.0%.
• Have nephrotic syndrome, dysproteinemias, or severe renal failure (glomerular filtration rate [GFR] < 30 mL/minute, as calculated from creatinine clearance).
• Have had unstable angina or an acute myocardial infarction (MI) within three months of the Screening Visit.
• Have had severe peripheral artery disease as evidenced by intermittent claudication within three months of the Screening Visit.
• Have had uncontrolled cardiac arrhythmias within three months of the Screening Visit.
• Have symptomatic heart failure defined as dyspnea at rest or with exertion (mild peripheral edema is not exclusionary).
• Have a systolic blood pressure measurement of > 180 mmHg or a diastolic blood pressure measurement of > 110 mmHg at the Screening or Baseline Visit
• Have active gout or uric acid >= 11 mg/dL.
• Have a history of hepatitis (acute or chronic), obstructive liver disease, or alanine aminotransferase (ALT; serum glutamic pyruvic transaminase [SGPT]) or aspartate aminotransferase (AST; serum glutamic oxaloacetic transaminase [SGOT]) values >= 1.3 times the upper limit of normal (ULN) at the Screening Visit.
• Have creatine phosphokinase (CPK) >= 3 x ULN at the Screening Visit.
• Have used an investigational study drug or participated in an investigational study within 30 days of the Screening Visit.
• Have a health condition or laboratory abnormality (inclusive of clinically significant laboratory results at Screening Visit), which, in the opinion of the Investigator, may be adversely affected by the procedures or study medications in this study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NER/ASA Placebo	Niacin extended-release (NER)	-
NER/ASA	Niacin extended-release (NER)	-
NER/ASA	Aspirin (ASA)	-
NER/ASA Placebo	Aspirin (ASA) placebo	-
NER Placebo/ASA Placebo	Niacin extended-release (NER) placebo	-
NER Placebo/ASA Placebo	Aspirin (ASA) placebo	-

Primary Outcome Measures

Name	Time	Method
Flushing ASsessment Tool (FAST) Test-retest Reliability--mean Flushing Severity Score	Week 1 to Week 2	Test-retest reliability of the mean flushing severity score was evaluated. The intraclass correlation coefficient comparing flushing severity scores for Week 1 and Week 2 was examined to determine test-retest reliability. Flushing severity was assessed using the FAST on a scale of 1 to 10, with 10 being the most severe.
FAST Test-retest Reliability--maximum Flushing Severity Score	Week 1 to Week 2	Test-retest reliability of the maximum flushing severity score was evaluated. The intraclass correlation coefficient comparing flushing severity scores for Week 1 and Week 2 was examined to determine test-retest reliability. Flushing severity was assessed using the FAST on a scale of 1 to 10, with 10 being the most severe.
FAST Cross-sectional Construct Validity--mean Flushing Severity Score	Week 1	The relationship between mean flushing severity and overall flushing troublesomeness was evaluated by examining the Spearman rank-order correlation. Flushing severity was assessed using the FAST on a scale of 1 to 10, with 10 being the most severe. Overall flushing troublesomeness was assessed using the FAST on a scale of 1 to 10, with 10 being the most troublesome.
FAST Cross-sectional Construct Validity--maximum Flushing Severity Score	Week 1	The relationship between maximum flushing severity and overall flushing troublesomeness was evaluated by examining the Spearman rank-order correlation. Flushing severity was assessed using the FAST on a scale of 1 to 10, with 10 being the most severe. Overall flushing troublesomeness was assessed using the FAST on a scale of 1 to 10, with 10 being the most troublesome.
FAST Longitudinal Construct Validity--mean Flushing Severity Score	Week 1 to Week 2	The relationship between the change in mean flushing severity scores from Week 1 to Week 2, and the subject-rated overall treatment effect scale administered at Week 2, was assessed by examining the Spearman rank-order correlation. Flushing severity was assessed using the FAST on a scale of 1 to 10, with 10 being the most severe. The overall treatment effect was assessed on a scale of 1 (symptoms are worse since study start), 2 (symptoms are about the same since study start), or 3 (symptoms are better since study start).
FAST Longitudinal Construct Validity--maximum Flushing Severity Score	Week 1 to Week 2	The relationship between the change in maximum flushing severity scores from Week 1 to Week 2, and the subject-rated overall treatment effect scale administered at Week 2, was assessed by examining the Spearman rank-order correlation. Flushing severity was assessed using the FAST on a scale of 1 to 10, with 10 being the most severe. The overall treatment effect was assessed on a scale of 1 (symptoms are worse since study start), 2 (symptoms are about the same since study start), or 3 (symptoms are better since study start).
FAST Responsiveness--mean Flushing Severity Score	Study start to Day 43	The change in mean flushing severity scores from study start to Day 43 was compared in subjects classified as responders vs. nonresponders. Flushing severity was assessed using the FAST on a scale of 1 to 10, with 10 being the most severe. Changes in mean flushing severity scores were negative if flushing symptoms improved and positive if flushing symptoms worsened.
FAST Responsiveness--maximum Flushing Severity Score	Study start to Day 43	The change in maximum flushing severity scores from study start to Day 43 was compared in subjects classified as responders vs. nonresponders. Flushing severity was assessed using the FAST on a scale of 1 to 10, with 10 being the most severe. Changes in maximum flushing severity scores were negative if flushing symptoms improved and positive if flushing symptoms worsened.

Secondary Outcome Measures

Name	Time	Method
Maximum Severity of Flushing Events Overall During the Study	Week 1 to Week 6	The severity of flushing events was assessed as none, mild, moderate, severe, or very severe using the FAST. The maximum severity of flushing events overall during the study was compared among treatment groups.