Clinical trial NCT01262625: Randomized Evaluation of Patients With Stable Angina Comparing Diagnostic Examinations
Official title: ACRIN-4701 RESCUE: Randomized Evaluation of Patients With Stable Angina Comparing Utilization of Diagnostic Examinations
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Chest Pain
Stable Angina Pectoris, CCS Class I to III
Angina Equivalent
Coronary Artery Disease
Keywords: stable angina
recurrent chest pain
chest pain
angina equivalent
diagnosis
coronary artery disease
Lead sponsor: American College of Radiology
Sponsor class: OTHER
First posted: 2010-12-17
Enrollment: 1050
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: DIAGNOSTIC

Brief summary: 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).

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Time-dependent Rates of the Composite Primary Endpoint Major Adverse Cardiovascular Event (MACE: Comprising Cardiac-related Death or Acute Myocardial Infarction (AMI), and Revascularization)
timeFrame: up to 24 Months (depends on time of trial enrollment and funding duration)
Secondary outcomes:
measure: 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)
timeFrame: 1 year
measure: Short Form-36 Survey (SF-36v2) and Seattle Angina Questionnaire (SAQ) Score
timeFrame: baseline and 12 months
measure: The Effectiveness of Each Arm Will be Measured in Terms of Life Years and Quality of Life Years (QALY).
timeFrame: Baseline and 1 year
Other outcomes:
Locations:
city: Decatur
country: United States
facility: Atlantic VA Medical Center
state: Georgia
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Salem
country: United States
facility: Salem VA Medical Center
state: Virginia
Study officials:
affiliation: Division of Cardiothoracic Imaging, Emory University
name: Arthur Stillman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mallinckrodt Institute of Radiology, Washington University of Medicine
name: Pamela K Woodard, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.