Clinical trial NCT01084239: Multicenter Study to Rule Out Myocardial Infarction by Cardiac Computed Tomography
Official title: Rule Out Myocardial Ischemia/Infarction by Computer Assisted Tomography
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Coronary Syndrome
Myocardial Infarction
Unstable Angina Pectoris
Keywords: acute chest pain
emergency department
cardiac computed tomography
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Kaiser Permanente
name: Beth Israel Deaconess Medical Center
name: Bay State Clinical Trials, Inc.
name: Washington University School of Medicine
name: Tufts Medical Center
name: The Cleveland Clinic
name: Northwestern University
name: University of Maryland
First posted: 2010-03-10
Enrollment: 1000
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: The growing availability of cardiac computed tomography (CT)\* in emergency departments (EDs) across the U.S. expands the opportunities for its clinical application, but also heightens the need to define its appropriate use in the evaluation of patients with acute chest pain. To address this need, we performed a randomized diagnostic trial (RDT) to determine whether integrating cardiac CT, along with the information it provides on coronary artery disease (CAD) and left ventricular (LV) function, can improve the efficiency of the management of these patients (i.e. shorten length of hospital stay, increase direct discharge rates from the ED, decreasing healthcare costs and improving cost effectiveness while being safe).

Detailed description: Patients with acute chest pain and normal or non-diagnostic electrocardiograms (ECGs) represent a cohort whose management is notably inefficient and diagnostically challenging. Because in less than 30% of EDs diagnostic testing (e.g. nuclear imaging, echocardiography, and exercise treadmill ECG) that would allow physicians to rule out the occurrence of myocardial ischemia is performed as part of the initial evaluation, most of these patients are hospitalized for 24 to 36 hours to exclude the presence of acute coronary syndrome (ACS). Of the six million acute chest pain patients admitted each year in the U.S. under these conditions, less than 10% of them ultimately receive a diagnosis of ACS at discharge. Moreover, inpatient care for negative evaluations imparts an economic burden in excess of $8 billion annually.

Since acute myocardial ischemia and necrosis are rare in the absence of coronary artery disease, a technology that reliably identifies CAD may allow physicians to discharge chest pain patients directly from the ED. Cardiac CT is a safe, high-speed, noninvasive imaging technique that accurately detects coronary atherosclerotic plaque and stenosis, and also allows physicians to assess global and regional LV function.

Observational studies have demonstrated that approximately 40% of acute chest pain patients have no evidence of atherosclerosis on cardiac CT, and that an additional 30% have no evidence of hemodynamically significant (\>50%) coronary artery stenosis. Both of these criteria are powerful predictors of the absence of both ACS and major adverse cardiovascular events (negative predictive value \[NPV\] of 98%). The specificity of cardiac CT is further increased when global and regional LV function is normal. Several studies have demonstrated that cardiac CT, with its high NPV, can be effectively used to rule out ACS, but little is known about the willingness ability of ED physicians to use this information to augment patient management.

We therefore performed a trial at 9 clinical sites and randomized 1000 patients with acute chest pain and normal or non-diagnostic ECGs, to receive either standard ED evaluation (no intervention) or a cardiac CT (experimental) in the evaluation of acute chest pain in the emergency room. (Rule Out Myocardial Infarction using Computer Assisted Computed Tomography \[ROMICAT II\]).

Eligibility criteria: Inclusion Criteria:

1. Participant had at least five minutes of chest pain or equivalent (chest tightness; pain radiating to left, right, or both arms or shoulders, back, neck, epigastrium, jaw/throat; or unexplained shortness of breath, syncope/presyncope, generalized weakness, nausea, or vomiting thought to be of cardiac origin) at rest or during exercise within 24 hours of ED presentation, warranting further risk stratification, as determined by an ED attending.
2. 2 or more cardiac risk factors (diabetes, hypertension, hyperlipidemia, current smoker and family history of coronary artery disease).
3. Able to provide a written informed consent.
4. \<75 years of age, but \>40 years of age.
5. Able to hold breath for at least 10 seconds.
6. Sinus rhythm.

Exclusion Criteria:

1. New diagnostic ischemic ECG changes (ST-segment elevation or depression \> 1 mm or T-wave inversion \> 4 mm) in more than two anatomically adjacent leads or left bundle branch block
2. Documented or self-reported history of CAD (MI, percutaneous coronary interventions \[PCIs\], coronary artery bypass graft \[CABG\], known significant coronary stenosis \[\>50%\])
3. Greater than 6 hours since presentation to ED.
4. BMI \>40 kg/m2
5. Impaired renal function as defined by serum creatinine \>1.5 mg/dL\*
6. Elevated troponin-T (\> 0.09 ng/ml)
7. Hemodynamically or clinically unstable condition (BP systolic \< 80 mm Hg, atrial or ventricular arrhythmias, persistent chest pain despite adequate therapy)
8. Known allergy to iodinated contrast agent
9. Currently symptomatic asthma
10. Documented or self-reported cocaine use within the past 48 hours (acute)
11. On Metformin therapy and unable or unwilling to discontinue for 48 hours after the CT scan
12. Contraindication to beta blockers (taking daily antiasthmatic medication): This exclusion only applies to patients with a heart rate \>65 bpm at sites using a non-dual source CT scanner
13. Participant with no telephone or cell phone numbers or no address (preventing follow-up)
14. Participant with positive pregnancy test. Women of childbearing potential, defined as \<2 years of menopause in the absence of hysterectomy or tube ligation, must have a pregnancy test performed within 24 hours before the CT scan.
15. Participant unwilling to provide a written informed consent.

Primary outcomes:
measure: Length of Hospital Stay
timeFrame: Duration of stay in the hospital during the initial visit
Secondary outcomes:
measure: Time to Diagnosis
timeFrame: Time from ED arrival to first positive test (all tests except Echocardiography Rest and including troponins ) if discharge diagnosis is ACS, otherwise time to performance of last test (all tests except Echocardiography Rest and including troponins ).
measure: Healthcare Utilization
timeFrame: Duration of stay in the hospital during the initial visit
measure: MACE
timeFrame: 72 hours after discharge up to 28 days after enrollment.
measure: Cost-effectiveness
timeFrame: Duration of stay in the hospital during the initial visit
measure: Rate of ED Discharge
timeFrame: Duration of stay in the hospital during the initial visit
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Udo Hoffmann, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Karady J, Mayrhofer T, Ferencik M, Nagurney JT, Udelson JE, Kammerlander AA, Fleg JL, Peacock WF, Januzzi JL Jr, Koenig W, Hoffmann U. Discordance of High-Sensitivity Troponin Assays in Patients With Suspected Acute Coronary Syndromes. J Am Coll Cardiol. 2021 Mar 30;77(12):1487-1499. doi: 10.1016/j.jacc.2021.01.046.
citation: Reinhardt SW, Babatunde A, Novak E, Brown DL. Effect of Race on Outcomes Following Early Coronary Computed Tomographic Angiography or Standard Emergency Department Evaluation for Acute Chest Pain. Ethn Dis. 2018 Oct 18;28(4):517-524. doi: 10.18865/ed.28.4.517. eCollection 2018 Fall.
citation: Bittner DO, Mayrhofer T, Puchner SB, Lu MT, Maurovich-Horvat P, Ghemigian K, Kitslaar PH, Broersen A, Bamberg F, Truong QA, Schlett CL, Hoffmann U, Ferencik M. Coronary Computed Tomography Angiography-Specific Definitions of High-Risk Plaque Features Improve Detection of Acute Coronary Syndrome. Circ Cardiovasc Imaging. 2018 Aug;11(8):e007657. doi: 10.1161/CIRCIMAGING.118.007657.
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