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

A Phase 3b, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of Caffeine Intake on Single Photon Emission Computed Tomography (SPECT) Myocardial Perfusion Imaging (MPI) in Subjects Administered Regadenoson

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

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease (CAD)
• Intervention / Treatment: Drug: placebo; Drug: regadenoson; Radiation: technetium; Drug: overencapsulated caffeine

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.

• Study Type: Interventional
• Enrollment (Actual): 347
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
    • Huntsville, Alabama, United States, 35801
  • California
    • La Mesa, California, United States, 91942
    • Mission Viejo, California, United States, 92691
    • Roseville, California, United States, 95661
    • Sacramento, California, United States, 95819
    • Santa Rosa, California, United States, 95405
  • Connecticut
    • Hartford, Connecticut, United States, 06102-5037
  • Delaware
    • Newark, Delaware, United States, 19173
  • Florida
    • Jacksonville, Florida, United States, 32216
    • Miami, Florida, United States, 33173
    • Tamarac, Florida, United States, 33321
  • Illinois
    • Aurora, Illinois, United States, 60504
  • Kansas
    • Overland Park, Kansas, United States, 66209
  • Maine
    • Auburn, Maine, United States, 04210
  • Massachusetts
    • Pittsfield, Massachusetts, United States, 01201
  • Michigan
    • Detroit, Michigan, United States, 48202
    • Ypsilanti, Michigan, United States, 48197
  • Missouri
    • Kansas City, Missouri, United States, 64111
  • New York
    • Albany, New York, United States, 12205
    • Rochester, New York, United States, 14642-8679
  • Ohio
    • Columbus, Ohio, United States, 43214
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19102
    • Wyomissing, Pennsylvania, United States, 19610
  • Tennessee
    • Knoxville, Tennessee, United States, 37920

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo plus Regadenoson; Two placebo capsules plus 0.4 mg regadenoson per 5mL intravenous (IV) bolus injection	Drug: placebo; oral; Drug: regadenoson; IV; Other Names: Lexiscan; CVT 3146; Radiation: technetium; IV; Other Names: sestamibi; tetrafosmin
Experimental: Caffeine 200 mg plus Regadenoson; One 200 mg Caffeine capsule and one placebo capsule plus 0.4 mg regadenoson per 5mL intravenous bolus injection	Drug: regadenoson; IV; Other Names: Lexiscan; CVT 3146; Radiation: technetium; IV; Other Names: sestamibi; tetrafosmin; Drug: overencapsulated caffeine; oral
Experimental: Caffeine 400 mg plus Regadenoson; Two 200 mg Caffeine capsules plus 0.4 mg regadenoson per 5mL intravenous bolus injection	Drug: regadenoson; IV; Other Names: Lexiscan; CVT 3146; Radiation: technetium; IV; Other Names: sestamibi; tetrafosmin; Drug: overencapsulated caffeine; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Number of Reversible Defects	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).	Day 3 and Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Summed Difference Score (SDS) Across All 17 Segments	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).	Day 3 and Day 5
Change in Number of Reversible Defects Assessed by Computerized Quantitation	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).	Day 3 and Day 5
Change in Summed Difference Score Across All 17 Segments Assessed by Computerized Quantitation	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).	Day 3 and Day 5
Change From Baseline in Heart Rate	Baseline is the last non-missing measurement on or before first dose of regadenoson Change is calculated as the time point minus baseline.	Baseline, Day 5 (-3 min), Day 5 (+3 min), Day 5 (+15 min)
Change From Baseline in Systolic Blood Pressure	Baseline is the last non-missing measurement on or before first dose of regadenoson. Change is calculated as the time point minus baseline.	Baseline, Day 5 (-3 min), Day 5 (+3 min), Day 5 (+15 min)
Change From Baseline in Diastolic Blood Pressure	Baseline is the last non-missing measurement on or before first dose of regadenoson. Change is calculated as the time point minus baseline.	Baseline, Day 5 (-3 min), Day 5 (+3 min), Day 5 (+15 min)

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Director: Use Central Contact, Astellas Pharma Global Development

Publications and helpful links

General Publications

• Tejani FH, Thompson RC, Iskandrian AE, McNutt BE, Franks B. Effect of caffeine on SPECT myocardial perfusion imaging during regadenoson pharmacologic stress: rationale and design of a prospective, randomized, multicenter study. J Nucl Cardiol. 2011 Feb;18(1):73-81. doi: 10.1007/s12350-010-9311-6. Epub 2010 Nov 17.

Helpful Links

• Link to results on Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2009
• Primary Completion (Actual): July 15, 2010
• Study Completion (Actual): July 15, 2010

Study Registration Dates

• First Submitted: January 21, 2009
• First Submitted That Met QC Criteria: January 21, 2009
• First Posted (Estimated): January 22, 2009

Study Record Updates

• Last Update Posted (Actual): December 3, 2024
• Last Update Submitted That Met QC Criteria: November 12, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: ischemia; pharmacologic stress; coronary artery disease (CAD)
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Neurotransmitter Agents; Purinergic Antagonists; Purinergic Agents; Central Nervous System Stimulants; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Purinergic P1 Receptor Agonists; Purinergic Agonists; Adenosine A2 Receptor Agonists; Caffeine; Regadenoson
• Other Study ID Numbers: 3606-CL-3002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR