ACRIN 4701: Randomized Evaluation of Patients with Stable Angina Comparing Utilization of Diagnostic Examinations (RESCUE)
Study Chair Co-Chair Arthur Stillman, MD, PhD Pamela Woodard, MD Div of Cardiothoracic Imaging Cardiovascular Imaging Laboratory Emory University Mallinckrodt Institute of Radiology, Washington 1364 Clifton Road NE Univ. School of Medicine Atlanta, GA 30322 510 S. Kingshighway Blvd. Phone: 404-712-7964 St. Louis, MO 63110 Fax: 404-712-7777 Phone: 314-362-9989 Email: [email protected] Fax: 314-747-3882 Email: [email protected]
Core Lab PI Co-PI Udo Hoffmann, MD, MPH Joao Lima, MD Associate Prof. of Radiology, Professor of Medicine and Radiology Harvard Medical School Director of Cardiovascular Imaging Director, MGH Cardiac MR PET CT Program Johns Hopkins University Massachusetts General Hospital, Boston 600 N. Wolfe Street, Blalock 524 165 Cambridge Street, Suite 400 Baltimore, MD 21287 Boston, MA 02114 Phone: 410-614-1284 Phone: 617-726-5954 Fax: 410-614-8222 Fax: 617-724-4152 Email: [email protected] Email: [email protected]
Study Statistician Core Lab Co-PI Constantine Gatsonis, PhD James E. Udelson, MD, FACC Center For Statistical Sciences Director, Nuclear Cardiology Laboratory Brown University, Box G-S121-7 Tufts-New England Medical Center 121 South Main Street 750 Washington Street, Box 70 Providence, RI 02912 Boston, MA 0211 Phone: 401-863-9183 Phone: 617-636-8066 Fax: 401-863-9182 Fax: 617-636-2276 Email: [email protected] Email: [email protected]
Epidemiologist Statistician Ilana Gareen, Ph.D. Tao Liu, PhD Center for Statistical Sciences Center For Statistical Sciences Brown University, Box G-S121-7 Brown University, Box G-121-7 121 South Main Street 121 South Main Street Providence, RI 02912 Providence, RI 02912 Phone: (401) 863-1758 Phone: 401-863-6480 Fax: (401) 863-9182 Fax: 401-863-9182 Email: [email protected] Email: t [email protected]
Adapted from Amendment 1, Version May 4, 2011 SCHEMA
Abbreviations: LM Dz: left main disease (≥ 50% stenosis) CAD: coronary artery disease MACE: major adverse cardiac event CCS: Canadian Cardiac Society MPI: myocardial perfusion imaging CCTA: coronary computed tomography angiography OMT: optimal medical therapy ECG: electrocardiogram SPECT: single photon emission tomography ICA: invasive coronary angiography TID: transient ischemic dilation
Websites: www.acrin.org/RESCUE_protocol.aspx (for trial conduct materials) www.rescuetrial.org (for participant educational materials)
Adapted from Amendment 1, Version May 4, 2011 Study Objectives/Specific Aims This randomized, controlled, diagnostic, multicenter trial will follow participants at 6-month intervals for up to 24 months to determine the incidence of MACE, defined as myocardial infarction (MI) or cardiac- related death, and cross-over to revascularization. (Some participants will be followed only up to 12 months, dependent on when they join the trial and due to trial timeline completion limitations.)
The primary endpoint of the study is a combined endpoint of occurrence of a MACE and revascularization. We will calculate differences in the combined MACE/revascularization endpoint between the CCTA and SPECT MPI arms.
Hypothesis Use of CCTA as a diagnostic tool for angina symptoms will be associated with no increase in MACE or revascularization, decreased cost, reduced risks (e.g., less radiation exposure), additional insights into alternate explanations of chest pain, and increased cost-effectiveness in comparison with use of SPECT MPI.
Sample Size A total of 4300 patients will be randomized to CCTA or SPECT MPI/ICA for diagnostic assessment of angina at up to 80 institutions internationally.
NOTE: Physicians referring patients to be enrolled in RESCUE must be agreeable to an initial trial of OMT (non-revascularization) after imaging in patients with symptoms of stable angina and documented CAD by either CCTA or SPECT without left main disease. Patients with persistent or worsening symptoms while on OMT may proceed to revascularization at the referring physician’s discretion.
Inclusion Criteria Willing and able to provide a written informed consent; 40 years of age or older; Presentation with symptoms of stable angina (CCS Class I to III) or angina equivalent with or without known CAD; Planned non-invasive imaging for CAD diagnosis; Able to tolerate CCTA or SPECT MPI per randomization as required by protocol, to be performed at an ACRIN-qualified facility with a RESCUE-qualified scanner.
Exclusion Criteria Prior revascularization; Renal insufficiency or renal failure; History of allergy-like reaction to iodinated contrast; Atrial fibrillation or significant arrhythmia judged to potentially limit quality of CCTA; Acute ischemia; Acute myocardial infarction; Severe myocardial ischemia: known markedly positive exercise treadmill stress test (significant ST segment depressions or hypotensive response during stage I of the Bruce protocol); Unable to suspend respiration for 15 seconds or to follow instructions to do so; Unstable angina and symptoms refractory to maximal oral and intravenous medical therapy (persistent CCS class IV); History of known left ventricular ejection fraction < 45%;
Adapted from Amendment 1, Version May 4, 2011 Pulmonary edema or heart failure unresponsive to standard medical therapy; Pacemaker; Valvular heart disease likely to require surgery in the next 18 months; Congenital heart disease or cardiomyopathy likely to affect prognosis during follow up; Significant systemic hypertension (blood pressure > 200/100 mm Hg) unresponsive to medical therapy; Severe noncardiovascular comorbidity limiting survival (e.g., cancer or other life threatening illness for which the patient is expected to live less than 12 months); Prior imaging evaluation for this episode of symptoms (e.g., SPECT MPI or CCTA within the previous 72 hours); BMI > 40 kg/m2; Pregnancy.
Adapted from Amendment 1, Version May 4, 2011 Visit 1: Phase 1 – Baseline Visit 1: Phase 2 – Visit 1: Phase 3 A – Visit 1: Phase 3B – Visit 1: Phase 4 – Treatment Based Follow-up: Assessment Registration and Group A (CCTA) Group B (SPECT on CCTA or SPECT MPI Results 6-Month Intervals for Randomization MPI) Up to 24 Months After Enrollment Obtain a signed informed Register the eligible Pre-treatment SPECT MPI Depending on diagnostic study results, Follow-up at the site consent form participant with heart-rate lowering completed per participant is prescribed OMT or goes level will comprise drug and/or institutional to ICA for additional assessment telephone contact with Perform baseline assessment Receive randomization nitroglycerin depending standard practices the participant or proxy to determine eligibility, assignment to Group A Participants with CCTA findings of a on participant heart rate and Section 9.2 of for additional medical including kidney health (CCTA) or Group B stenosis ≥ 50% in diameter will be and imaging equipment the trial protocol information. assessment and pregnancy (SPECT MPI) treated with OMT unless it is in left test as appropriate Introduce intravenous main (leading to diagnostic ICA) For participants with Schedule CCTA or (IV) catheter for positive diagnostic Collect ECG and lab results SPECT MPI to be Participants with moderate – severe contrast administration findings: Contact at 2 completed within 2 weeks ischemia by SPECT MPI (≥ 10% Obtain contact information: weeks and 2 months. of consent Administer iodinated reversible perfusion defect) or two (2) phone numbers for contrast agent evidence of TID accompanied by ECG All participants, participant (if possible), changes of ischemia will go to ICA regardless of diagnostic phone number of proxy, Complete CCTA per and then be treated with OMT if findings, will be Social Security Number, and protocol specifications findings of a stenosis ≥ 50% in contacted every 6 self-addressed postcard Assess for AEs diameter months for up to 2 years: completed by participant 6, 12, 18, and/or 24 Participants with CCTA findings of U.S. Sites Only: Administer months after enrollment stenosis < 50% in diameter will be SAQ and SF-36 for to the trial; number of discharged or obtain treatment per participant to complete contacts will depend on institutional standard of care (assistance should be when the participant limited; research staff will Participants with SPECT MPI findings joins the trial and when be trained on appropriate of reversible ischemia < 10% of the funding for the trial responses to participant myocardium or reversible ischemia ends. Lifestyle questions queries) Foreign sites are ≥ 10% of the myocardium or evidence will be included in the exempt from the QoL of TID accompanied by ECG changes follow-up assessment component. of ischemia who go to ICA and Quality-of-life subsequent findings are a stenosis Administer lifestyle questionnaires at 1-yr < 50% in diameter will be discharged questions. will be administered for or obtain treatment per institutional a subset of participants standard of care by U.S. sites only
Adapted from Amendment 1, Version May 4, 2011