Randomized Evaluation of Patients With Stable Angina Comparing Diagnostic Examinations (RESCUE)

ACRIN-4701 RESCUE: Randomized Evaluation of Patients With Stable Angina Comparing Utilization of Diagnostic Examinations

This randomized, controlled, diagnostic, multicenter trial will compare two diagnostic imaging pathways--coronary computed tomography angiography (CCTA) and single photon emission tomography (SPECT) myocardial perfusion imaging (MPI)--to determine the incidence of major adverse coronary events (MACE), defined as myocardial infarction (MI) or cardiac-related death, and cross-over to revascularization. CCTA may be used to direct patients with symptoms of stable angina or angina equivalent to optimal medical therapy (OMT). The 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/invasive coronary angiography (ICA).

Study Overview

• Status: Terminated
• Conditions: Coronary Artery Disease; Chest Pain; Stable Angina Pectoris, CCS Class I to III; Angina Equivalent
• Intervention / Treatment: Device: CCTA; Device: SPECT MPI/ICA

Detailed Description

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 using computer-aided diagnosis (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.

• Study Type: Interventional
• Enrollment (Actual): 1050
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Atlantic VA Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Virginia
    • Salem, Virginia, United States, 24153
      • Salem VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 (ST) [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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: CCTA Diagnostic; Participants randomized to diagnostic evaluation using coronary computed tomographic angiography (CCTA) to determine therapeutic course of action.	Device: CCTA; Complete diagnostic CCTA per protocol specifications.; Other Names: coronary CT; cardiac CT; coronary computed tomographic angiography
Active Comparator: Group B: SPECT MPI/ICA Diagnostic; Standard-of-care diagnostic assessment using single photon emission computed tomography myocardial perfusion imaging (SPECT MPI), possibly followed by diagnostic invasive coronary angiography (ICA) dependent on SPECT MPI results.	Device: SPECT MPI/ICA; Perform SPECT MPI per institutional standard practice; diagnostic ICA will be performed only as indicated per protocol.; Other Names: nuclear medicine cardiac stress test; stress test; cardiac stress test; exercise cardiac stress test; pharmacologic cardiac stress test; nuclear medicine stress test; single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-dependent Rates of the Composite Primary Endpoint Major Adverse Cardiovascular Event (MACE: Comprising Cardiac-related Death or Acute Myocardial Infarction (AMI), and Revascularization)	To compare outcomes of participants with symptoms of stable angina or angina equivalent evaluated with an anatomic imaging strategy using CCTA as initial method of computer-aided diagnosis (CAD) (Group A) to a combined functional and anatomic imaging strategy of SPECT MPI/ICA (Group B) as a guide to Optimal Medical Therapy (OMT) alone. The analysis was conducted from an intent-to-treat perspective	up to 24 Months (depends on time of trial enrollment and funding duration)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prediction of Response (MACE/Revascularization) at 1 Year Using: Modified Duke Score or CCTA + AHA 16 Predictor/CCTA+AHA 16+Clinical Data Predictor or SPECT% Reversible Defect Size Reported as Receiver Operating Characteristic (ROC) Area Under Curve (AUC)	AUC is a unitless measure of performance ranging form 0.5 (guessing) to 1.0 (perfect predictor) that can be thought of a the proportion of correct classifications in a 2-alternative-forced-choice experiment - and for binary outcomes, it is equivalent to the C-statistic. It will be used to evaluate and compare the ability of available prognostic indices and SPECT-MPI % reversible defect size to predict revascularization or MACE using CCTA information: A CCTA Modified Duke index A CCTA index including the 16 individual American Heart Association (AHA) segments A CCTA including the 16 individual AHA segments and clinical data and compare them to the SPECT % reversible defect size results	1 year
Short Form-36 Survey (SF-36v2) and Seattle Angina Questionnaire (SAQ) Score	SF36+SAQ at baseline and to a subset of participants, stratified by diagnostic examination, at 12 months after enrollment to monitor angina symptoms and their impact on Quality of life. The Short Form-36 (SF36) is a 36 item overall health status/Quality of Life collected in 8 domains. Scales are standardized with scores ranging from 0-100. Higher scores= better health status. The Seattle Angina Questionnaire (SAQ) is a self-administered, 19-item, cardiac disease-related quality-of-life measure collected in 5 domains. scales are standardized with scores ranging from 0-100. Higher scores= better health status. Positive cardiac findings on diagnostic testing are defined as: 50% stenosis on CCTA or un-evaluable left main, or proximal and mid segments of all other epicardial arteries (right coronary artery, left anterior descending artery, or left circumflex artery); and; 10% reversible defect on SPECT MPI or evidence of Transient Ischemic Dilation (TID) accompanied by ECG	baseline and 12 months
The Effectiveness of Each Arm Will be Measured in Terms of Life Years and Quality of Life Years (QALY).	International medical records will be used to determine mortality which may not be feasible at all participating international sites. Utilities will be based on Quality of Well Being scores converted from the SF-36 assessments The analysis will be performed assuming a societal perspective and lifetime time horizon	Baseline and 1 year

Collaborators and Investigators

• Sponsor: American College of Radiology
• Investigators: Principal Investigator: Arthur Stillman, MD, PhD, Division of Cardiothoracic Imaging, Emory University; Study Chair: Pamela K Woodard, MD, Mallinckrodt Institute of Radiology, Washington University of Medicine

Publications and helpful links

General Publications

• Boden WE, O'Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, Knudtson M, Dada M, Casperson P, Harris CL, Chaitman BR, Shaw L, Gosselin G, Nawaz S, Title LM, Gau G, Blaustein AS, Booth DC, Bates ER, Spertus JA, Berman DS, Mancini GB, Weintraub WS; COURAGE Trial Research Group. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007 Apr 12;356(15):1503-16. doi: 10.1056/NEJMoa070829. Epub 2007 Mar 26.
• Shaw LJ, Berman DS, Maron DJ, Mancini GB, Hayes SW, Hartigan PM, Weintraub WS, O'Rourke RA, Dada M, Spertus JA, Chaitman BR, Friedman J, Slomka P, Heller GV, Germano G, Gosselin G, Berger P, Kostuk WJ, Schwartz RG, Knudtson M, Veledar E, Bates ER, McCallister B, Teo KK, Boden WE; COURAGE Investigators. Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy. Circulation. 2008 Mar 11;117(10):1283-91. doi: 10.1161/CIRCULATIONAHA.107.743963. Epub 2008 Feb 11.
• Stillman AE, Gatsonis C, Lima JAC, Liu T, Snyder BS, Cormack J, Malholtra V, Schnall MD, Udelson JE, Hoffmann U, Woodard PK; RESCUE investigators *. Coronary Computed Tomography Angiography Compared With Single Photon Emission Computed Tomography Myocardial Perfusion Imaging as a Guide to Optimal Medical Therapy in Patients Presenting With Stable Angina: The RESCUE Trial. J Am Heart Assoc. 2020 Dec 15;9(24):e017993. doi: 10.1161/JAHA.120.017993. Epub 2020 Dec 5.

Helpful Links

• Visit ACR clinical research web site to view,trial protocols, contact information, recruitment materials, and other trial-related materials.

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2011
• Primary Completion (Actual): November 26, 2014
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: December 15, 2010
• First Submitted That Met QC Criteria: December 15, 2010
• First Posted (Estimated): December 17, 2010

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 22, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: chest pain; coronary artery disease; stable angina; diagnosis; recurrent chest pain; angina equivalent
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pain; Neurologic Manifestations; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Chest Pain; Angina Pectoris; Angina, Stable
• Other Study ID Numbers: ACRIN 4701 RESCUE; 1R01HS019403 (U.S. AHRQ Grant/Contract)