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Caffeine's Effect on Regadenoson Administration With Single Photon Emission Computed Tomography (SPECT) Myocardial Perfusion Imaging (MPI)

Phase 3
Completed
Conditions
Coronary Artery Disease (CAD)
Interventions
Radiation: technetium
Drug: placebo
Registration Number
NCT00826280
Lead Sponsor
Astellas Pharma Inc
Brief Summary

Observe whether the administration of caffeine prior to regadenoson will affect the interpretation of test results in subjects with coronary artery disease (CAD) undergoing SPECT MPI

Detailed Description

All subjects will undergo rest and stress scans. Those subjects who qualify by demonstrating at least 1 reversible defect, will undergo a third scan. All stress scans will involve the injection of regadenoson as the pharmacologic stress agent. Prior to the third scan, the subject will be administered blinded capsules of placebo or caffeine.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
347
Inclusion Criteria
  • Subject must have undergone a previous diagnostic study [e.g., SPECT, echocardiography, magnetic resonance imaging (MRI), etc.] for a clinical indication demonstrating evidence of reversible defects in ≥ 1 vascular segment, have had other stress testing within the past 3 months, or the subject's history suggests at least a 50% likelihood of CAD

    • If the previous diagnostic study shows only 1 reversible defect and it is in segment 17, another reversible defect will need to be present
  • Subject with CAD must have an intermediate/low-risk for immediate intervention

  • Subject must ingest caffeinated food or beverages regularly (at least the equivalent of one cup of caffeinated coffee daily)

  • Subject must agree to not ingest any caffeine or other foods containing methylxanthine at least 24 hours prior to each study visit

  • Subject must agree to abstain from eating solid food or drinking liquids other than water for at least 30 minutes prior to each study visit and 30 minutes following each study visit

Exclusion Criteria
  • Subject with documented myocardial infarction (MI) ≤ 30 days prior to enrollment
  • Subject with history of percutaneous coronary intervention (PCI) ≤ 4 weeks prior to enrollment
  • Subject with history of coronary artery bypass graft (CABG) ≤ 8 weeks prior to enrollment
  • Subject has prior history of heart transplantation
  • Subject has unstable angina, known severe left main coronary artery stenosis, severe heart failure, uncontrolled arrhythmias, symptomatic hypotension or severe hypertension (systolic blood pressure < 90 or > 180 mmHg, respectively), or > 1st degree atrioventricular block in the absence of a functioning pacemaker
  • Subject requires emergent cardiac medical intervention or catheterization
  • Subject has a history of smoking, regardless of frequency, tobacco type or method of intake, or using any smoking cessation products, including but not limited to the nicotine patch or nicotine gum, within 3 months prior to first dose of regadenoson
  • Subject is currently undergoing treatment with theophylline, or theophylline containing medications within 7 days prior to randomization (Day 3)
  • Subject has a history of known or suspected bronchoconstrictive or bronchospastic lung disease [e.g., asthma, wheezing, chronic obstructive pulmonary disease (COPD), etc.]
  • Subject has a history of diabetes associated with gastric disorders and/or emptying
  • Subject has end stage renal disease (ESRD) with a GFR< 15mL/min or currently undergoing dialysis for ESRD

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo plus RegadenosonplaceboTwo placebo capsules plus 0.4 mg regadenoson per 5mL intravenous (IV) bolus injection
Placebo plus RegadenosontechnetiumTwo placebo capsules plus 0.4 mg regadenoson per 5mL intravenous (IV) bolus injection
Caffeine 200 mg plus RegadenosontechnetiumOne 200 mg Caffeine capsule and one placebo capsule plus 0.4 mg regadenoson per 5mL intravenous bolus injection
Caffeine 400 mg plus RegadenosontechnetiumTwo 200 mg Caffeine capsules plus 0.4 mg regadenoson per 5mL intravenous bolus injection
Caffeine 200 mg plus Regadenosonoverencapsulated caffeineOne 200 mg Caffeine capsule and one placebo capsule plus 0.4 mg regadenoson per 5mL intravenous bolus injection
Caffeine 400 mg plus Regadenosonoverencapsulated caffeineTwo 200 mg Caffeine capsules plus 0.4 mg regadenoson per 5mL intravenous bolus injection
Placebo plus RegadenosonregadenosonTwo placebo capsules plus 0.4 mg regadenoson per 5mL intravenous (IV) bolus injection
Caffeine 200 mg plus RegadenosonregadenosonOne 200 mg Caffeine capsule and one placebo capsule plus 0.4 mg regadenoson per 5mL intravenous bolus injection
Caffeine 400 mg plus RegadenosonregadenosonTwo 200 mg Caffeine capsules plus 0.4 mg regadenoson per 5mL intravenous bolus injection
Primary Outcome Measures
NameTimeMethod
Change in Number of Reversible DefectsDay 3 and Day 5

Each segment of the 17-Segment Model was assessed for radiotracer uptake on a scale of 0 (normal uptake) to 4 (absent uptake). Segments were counted as having a reversible defect if the stress score was greater than the rest score and the stress score was ≥ 2. Change was calculated as the number of reversible defects using regadenoson with caffeine/placebo (Day 5) minus the number of reversible defects using regadenoson alone (Day 3).

Secondary Outcome Measures
NameTimeMethod
Change in Summed Difference Score (SDS) Across All 17 SegmentsDay 3 and Day 5

The Summed Difference Score was calculated as the difference in the Summed Stress Score across the 17 segments (scan run under stress condition) minus the Summed Rest Score across the 17 segments (scan run under rest conditions). Change in SDS was calculated as the SDS for regadenoson with caffeine/placebo stress scan (Day 5) minus the SDS for regadenoson only stress scan (Day 3). The full range of the SDS is -68 to 68, where 0 represents no change between Summed Stress Score and Summed Rest Score. A higher positive score indicates more severe coronary artery disease (CAD).

Change in Number of Reversible Defects Assessed by Computerized QuantitationDay 3 and Day 5

Each segment of the 17-Segment Model was assessed for radiotracer uptake on a scale of 0 (normal uptake) to 4 (absent uptake). Segments were counted as having a reversible defect if the stress score was greater than the rest score and the stress score was ≥ 2. Change was calculated as the number of reversible defects using regadenoson with caffeine/placebo (Day 5) minus the number of reversible defects using regadenoson alone (Day 3).

Change in Summed Difference Score Across All 17 Segments Assessed by Computerized QuantitationDay 3 and Day 5

The Summed Difference Score was calculated as the difference in the Summed Stress Score across the 17 segments (scan run under stress condition) minus the Summed Rest Score across the 17 segments (scan run under rest conditions). Change in SDS was calculated as the SDS for regadenoson with caffeine/placebo stress scan (Day 5) minus the SDS for regadenoson only stress scan (Day 3). The full range of the SDS is -68 to 68, where 0 represents no change between Summed Stress Score and Summed Rest Score. A higher positive score indicates more severe coronary artery disease (CAD).

Change From Baseline in Heart RateBaseline, Day 5 (-3 min), Day 5 (+3 min), Day 5 (+15 min)

Baseline is the last non-missing measurement on or before first dose of regadenoson Change is calculated as the time point minus baseline.

Change From Baseline in Systolic Blood PressureBaseline, Day 5 (-3 min), Day 5 (+3 min), Day 5 (+15 min)

Baseline is the last non-missing measurement on or before first dose of regadenoson. Change is calculated as the time point minus baseline.

Change From Baseline in Diastolic Blood PressureBaseline, Day 5 (-3 min), Day 5 (+3 min), Day 5 (+15 min)

Baseline is the last non-missing measurement on or before first dose of regadenoson. Change is calculated as the time point minus baseline.

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