Randomized Evaluation of Patients With Stable Angina Comparing Diagnostic Examinations

The Randomized Evaluation of Patients with Stable Angina Comparing Utilization of Diagnostic
Examinations (RESCUE) is a multi-center randomized, controlled trial responding to the need
for comparative analysis of these imaging technologies and the role of OMT in clinical care.
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. This study builds on the
results of the COURAGE trial by comparing CCTA and SPECT MPI/ICA integrated into a care
paradigm featuring initial treatment with OMT for patients diagnosed with CAD without
significant disease in the left main coronary artery. Participants will be followed for a
composite endpoint of MACE and cross-over to revascularization over a follow-up period up to
two years (two to six time points depending on diagnostic results and time of enrollment into
the trial). The primary endpoint of the study is a combined endpoint of occurrence of MACE
and revascularization. We will calculate differences in the combined MACE/revascularization
endpoint between the CCTA and SPECT MPI/ICA arms. Participant outcomes will be assessed by
age, gender, comorbidity, and angina classification class at presentation. Several
comparative-effectiveness analyses will be performed. We hypothesize that the CCTA arm will
be associated with no increase in MACE or revascularization, decreased cost, reduced risks
(e.g., less radiation exposure), additional insights into or alternate explanations of chest
pain, and increased cost-effectiveness in comparison with SPECT MPI/ICA. Findings are
expected to result in validation of an evolving new standard of care for patients with stable
angina that takes advantage of CCTA and OMT to more cost-effectively drive appropriate care
while reducing the need for invasive diagnosis and increased radiation exposure with SPECT
MPI/ICA.

Inclusion Criteria:

- Willing and able to provide a written informed consent;

- 40 years 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;

- Not suitable to undergo CT with an iodinated contrast agent:

- Known allergy-like reaction to contrast media as defined by the American College
of Radiology (ACR) (see
www.acr.org/SecondaryMainMenuCategories/quality_safety/contrast_manual.aspx for
reaction definition) or moderate to severe allergic reactions to more than one
allergen;

- Renal failure, as determined by glomerular filtration rate (GFR) < 30 mL/min/1.73
m2 based on a serum creatinine level obtained within 28 days prior to
registration;

- Renal insufficiency at the time of enrollment, as determined by GFR 30 to 60
mL/min/1.73 m2 based on a serum creatinine level obtained within 28 days prior to
registration, unless permitted by the institution's policy and/or ACR guidance for
risk reduction strategies (see
www.acr.org/SecondaryMainMenuCategories/quality_safety/contrast_manual.aspx for
guidance on contrast selection and pre-treatment strategies);

- 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%;

- 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 or intent to become pregnant (if a female is of childbearing
potential—defined as a premenopausal female capable of becoming pregnant—a pregnancy
test should be done prior to enrollment).