Multicenter Study to Rule Out Myocardial Infarction by Cardiac Computed Tomography (ROMICAT-II)

• ClinicalTrials.gov Identifier: NCT01084239
• Recruitment Status: Completed
• First Posted: March 10, 2010
• Results First Posted: May 7, 2014
• Last Update Posted: May 7, 2014
• Sponsor: Massachusetts General Hospital
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Kaiser Permanente; Beth Israel Deaconess Medical Center; Bay State Clinical Trials, Inc.; Washington University School of Medicine; Tufts Medical Center; The Cleveland Clinic; Northwestern University; University of Maryland
• Information provided by (Responsible Party): Udo Hoffmann, MD MPH, Massachusetts General Hospital

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
• Conditions: Acute Coronary Syndrome; Myocardial Infarction; Unstable Angina Pectoris
• Intervention: Radiation: Cardiac Computed Tomography
• Enrollment: 1000

Participant Flow

Recruitment Details	Patient enrollment began on April 23, 2010, and ended on January 30, 2012, at nine hospitals in the United States.
Pre-assignment Details

Arm/Group Title	Cardiac CT	Standard of Care
Arm/Group Description	Subjects in this arm (50% of the total cohort) were randomized to receive a cardiac computed tomography scan as part of the initial evaluation of acute chest pain symptoms, upon presentation to the emergency department. Cardiac Computed Tomography : A contrast enhanced cardiac CT was performed in addition to standard evaluation. Reconstructed data sets were evaluated for the presence of coronary artery calcium, coronary atherosclerotic plaque and stenosis, LV function and incidental findings.	Subjects in this arm (50% of the total cohort) continued to receive standard non-invasive evaluation of acute chest pain symptoms in the emergency department - mostly comprising of, but not limited to - exercise treadmill test, stress test with imaging and stress echocardiography.
Period Title: Randomization - Index Hospitalization
Started	501	499
Completed	501	499
Not Completed	0	0
Period Title: 28-Day Follow-up
Started	501 [1]	499
Completed	497	490
Not Completed	4	9
Reason Not Completed
Lost to Follow-up	4	9
[1] All 501 patients enrolled were evaluated for follow-up at 28 days.

Baseline Characteristics

Arm/Group Title		Cardiac CT	Standard of Care	Total
Arm/Group Description		Subjects in this arm (50% of the total cohort) were randomized to receive a cardiac computed tomography scan as part of the initial evaluation of acute chest pain symptoms, upon presentation to the emergency department. Cardiac Computed Tomography : A contrast enhanced cardiac CT was performed in addition to standard evaluation. Reconstructed data sets were evaluated for the presence of coronary artery calcium, coronary atherosclerotic plaque and stenosis, LV function and incidental findings.	Subjects in this arm (50% of the total cohort) continued to receive standard non-invasive evaluation of acute chest pain symptoms in the emergency department - mostly comprising of, but not limited to - exercise treadmill test, stress test with imaging and stress echocardiography.	Total of all reporting groups
Overall Number of Baseline Participants		501	499	1000
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	501 participants	499 participants	1000 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	433 86.4%	440 88.2%	873 87.3%
	>=65 years	68 13.6%	59 11.8%	127 12.7%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	501 participants	499 participants	1000 participants
		54 (8)	54 (8)	54 (8)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	501 participants	499 participants	1000 participants
	Female	239 47.7%	229 45.9%	468 46.8%
	Male	262 52.3%	270 54.1%	532 53.2%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	501 participants	499 participants	1000 participants
		501	499	1000

Outcome Measures

1. Primary Outcome

Title	Length of Hospital Stay
Description	[Not Specified]
Time Frame	Duration of stay in the hospital during the initial visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cardiac CT	Standard of Care
Arm/Group Description:	Subjects in this arm (50% of the total cohort) will be randomized to receive a cardiac computed tomography scan as part of the initial evaluation of acute chest pain symptoms, upon presentation to the emergency department. Cardiac Computed Tomography : A contrast enhanced cardiac CT will be performed in addition to standard evaluation. Reconstructed data sets will be evaluated for the presence of coronary artery calcium, coronary atherosclerotic plaque and stenosis, LV function and incidental findings.	Subjects in this arm (50% of the total cohort) will continue to receive standard non-invasive evaluation of acute chest pain symptoms in the emergency department - mostly comprising of, but not limited to - exercise treadmill test, stress test with imaging and stress echocardiography.
Overall Number of Participants Analyzed	501	499
Mean (Standard Deviation); Unit of Measure: hours
	23.2 (37.0)	30.8 (28.0)

2. Secondary Outcome

Title	Time to Diagnosis
Description	[Not Specified]
Time Frame	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 ).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cardiac CT	Standard of Care
Arm/Group Description:	Subjects in this arm (50% of the total cohort) were randomized to receive a cardiac computed tomography scan as part of the initial evaluation of acute chest pain symptoms, upon presentation to the emergency department. Cardiac Computed Tomography : A contrast enhanced cardiac CT was performed in addition to standard evaluation. Reconstructed data sets were evaluated for the presence of coronary artery calcium, coronary atherosclerotic plaque and stenosis, LV function and incidental findings.	Subjects in this arm (50% of the total cohort) continued to receive standard non-invasive evaluation of acute chest pain symptoms in the emergency department - mostly comprising of, but not limited to - exercise treadmill test, stress test with imaging and stress echocardiography.
Overall Number of Participants Analyzed	501	499
Mean (Standard Deviation); Unit of Measure: hours
	10.4 (12.6)	18.7 (11.8)

3. Secondary Outcome

Title	Healthcare Utilization
Description	Number of patients with diagnostic testing (CCTA, ETT, SPECT, stress echocardiography, and invasive coronary angiography)
Time Frame	Duration of stay in the hospital during the initial visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cardiac CT	Standard of Care
Arm/Group Description:	Subjects in this arm (50% of the total cohort) were randomized to receive a cardiac computed tomography scan as part of the initial evaluation of acute chest pain symptoms, upon presentation to the emergency department. Cardiac Computed Tomography : A contrast enhanced cardiac CT was performed in addition to standard evaluation. Reconstructed data sets were evaluated for the presence of coronary artery calcium, coronary atherosclerotic plaque and stenosis, LV function and incidental findings.	Subjects in this arm (50% of the total cohort) continued to receive standard non-invasive evaluation of acute chest pain symptoms in the emergency department - mostly comprising of, but not limited to - exercise treadmill test, stress test with imaging and stress echocardiography.
Overall Number of Participants Analyzed	501	499
Measure Type: Number; Unit of Measure: participants
	492	390

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cardiac CT, Standard of Care
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	Result for index hospitalization

4. Secondary Outcome

Title	MACE
Description	Major Adverse Cardiovascular Events, All though these events are called MACE they do not qualify as adverse or serious adverse events. As these events are expected in some individuals in this population. Only MACE that occured within 72 hours after hospital discharge were considered serious adverse events in this trial. There were no such events.
Time Frame	72 hours after discharge up to 28 days after enrollment.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cardiac CT	Standard of Care
Arm/Group Description:	Subjects in this arm (50% of the total cohort) were randomized to receive a cardiac computed tomography scan as part of the initial evaluation of acute chest pain symptoms, upon presentation to the emergency department. Cardiac Computed Tomography : A contrast enhanced cardiac CT was performed in addition to standard evaluation. Reconstructed data sets were evaluated for the presence of coronary artery calcium, coronary atherosclerotic plaque and stenosis, LV function and incidental findings.	Subjects in this arm (50% of the total cohort) continued to receive standard non-invasive evaluation of acute chest pain symptoms in the emergency department - mostly comprising of, but not limited to - exercise treadmill test, stress test with imaging and stress echocardiography.
Overall Number of Participants Analyzed	501	499
Measure Type: Number; Unit of Measure: events
	6	2

5. Secondary Outcome

Title	Cost-effectiveness
Description	Total cost during index hospitalization
Time Frame	Duration of stay in the hospital during the initial visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cardiac CT	Standard of Care
Arm/Group Description:	Subjects in this arm (50% of the total cohort) were randomized to receive a cardiac computed tomography scan as part of the initial evaluation of acute chest pain symptoms, upon presentation to the emergency department. Cardiac Computed Tomography : A contrast enhanced cardiac CT was performed in addition to standard evaluation. Reconstructed data sets were evaluated for the presence of coronary artery calcium, coronary atherosclerotic plaque and stenosis, LV function and incidental findings.	Subjects in this arm (50% of the total cohort) continued to receive standard non-invasive evaluation of acute chest pain symptoms in the emergency department - mostly comprising of, but not limited to - exercise treadmill test, stress test with imaging and stress echocardiography.
Overall Number of Participants Analyzed	501	499
Mean (Standard Deviation); Unit of Measure: US Dollars
	4026 (6792)	3874 (5298)

6. Secondary Outcome

Title	Rate of ED Discharge
Description	Direct discharge from Emergency Department
Time Frame	Duration of stay in the hospital during the initial visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cardiac CT	Standard of Care
Arm/Group Description:	Subjects in this arm (50% of the total cohort) were randomized to receive a cardiac computed tomography scan as part of the initial evaluation of acute chest pain symptoms, upon presentation to the emergency department. Cardiac Computed Tomography : A contrast enhanced cardiac CT was performed in addition to standard evaluation. Reconstructed data sets were evaluated for the presence of coronary artery calcium, coronary atherosclerotic plaque and stenosis, LV function and incidental findings.	Subjects in this arm (50% of the total cohort) continued to receive standard non-invasive evaluation of acute chest pain symptoms in the emergency department - mostly comprising of, but not limited to - exercise treadmill test, stress test with imaging and stress echocardiography.
Overall Number of Participants Analyzed	501	499
Measure Type: Number; Unit of Measure: participants
	233	62

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Cardiac CT		Standard of Care
Arm/Group Description	Subjects in this arm (50% of the total cohort) were randomized to receive a cardiac computed tomography scan as part of the initial evaluation of acute chest pain symptoms, upon presentation to the emergency department. Cardiac Computed Tomography : A contrast enhanced cardiac CT was performed in addition to standard evaluation. Reconstructed data sets were evaluated for the presence of coronary artery calcium, coronary atherosclerotic plaque and stenosis, LV function and incidental findings.		Subjects in this arm (50% of the total cohort) continued to receive standard non-invasive evaluation of acute chest pain symptoms in the emergency department - mostly comprising of, but not limited to - exercise treadmill test, stress test with imaging and stress echocardiography.
All-Cause Mortality
	Cardiac CT		Standard of Care
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Cardiac CT		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/501 (0.00%)		0/499 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Cardiac CT		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/501 (1.00%)		1/499 (0.20%)
Eye disorders
RASH URTICARIAL * [1]	1/501 (0.20%)	1	0/499 (0.00%)	0
General disorders
Nausea and vomiting * [2]	1/501 (0.20%)	1	0/499 (0.00%)	0
Nausea * [3]	1/501 (0.20%)	1	0/499 (0.00%)	0
ALLERGIC REACTION *	2/501 (0.40%)	2	0/499 (0.00%)	0
THROMBOSIS ARTERIAL * [4]	0/501 (0.00%)	0	1/499 (0.20%)	1
* Indicates events were collected by non-systematic assessment; [1] The patient developed a mild urticarial rash (2 separate quarter sized patches, 1 superior-lateral to his right eye and 1 superior-medial to his left eye) and associated itchiness within minutes of the injection of IV contrast.; [2] one episode N/V after CTA contrast. Pt given 4mg zofran IV, symptoms resolved.; [3] Patient developed nausea immediately after administration of IV contrast, she has had IV contrast in the past without associated nausea.; [4] right groin pseudoaneurysm

Limitations and Caveats

Enrollment occurred only during weekday hours.

Lack of blinding to the intervention.

Results may not be applicable to populations we did not study (i.e. patients younger than 40 years of age and those older than 74 years of age).

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Pearl Zakroysky
• Organization: Massachusetts Genderal Hospital Biostatistics Center
• Phone: 617 724 0309
• EMail: pzakroysky@partners.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Karády 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.

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.

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.

Reinhardt SW, Lin CJ, Novak E, Brown DL. Noninvasive Cardiac Testing vs Clinical Evaluation Alone in Acute Chest Pain: A Secondary Analysis of the ROMICAT-II Randomized Clinical Trial. JAMA Intern Med. 2018 Feb 1;178(2):212-219. doi: 10.1001/jamainternmed.2017.7360.

Ferencik M, Mayrhofer T, Lu MT, Woodard PK, Truong QA, Peacock WF, Bamberg F, Sun BC, Fleg JL, Nagurney JT, Udelson JE, Koenig W, Januzzi JL, Hoffmann U. High-Sensitivity Cardiac Troponin I as a Gatekeeper for Coronary Computed Tomography Angiography and Stress Testing in Patients with Acute Chest Pain. Clin Chem. 2017 Nov;63(11):1724-1733. doi: 10.1373/clinchem.2017.275552. Epub 2017 Sep 18.

Bittner DO, Mayrhofer T, Bamberg F, Hallett TR, Janjua S, Addison D, Nagurney JT, Udelson JE, Lu MT, Truong QA, Woodard PK, Hollander JE, Miller C, Chang AM, Singh H, Litt H, Hoffmann U, Ferencik M. Impact of Coronary Calcification on Clinical Management in Patients With Acute Chest Pain. Circ Cardiovasc Imaging. 2017 May;10(5). pii: e005893. doi: 10.1161/CIRCIMAGING.116.005893.

Truong QA, Schulman-Marcus J, Zakroysky P, Chou ET, Nagurney JT, Fleg JL, Schoenfeld DA, Udelson JE, Hoffmann U, Woodard PK. Coronary CT Angiography Versus Standard Emergency Department Evaluation for Acute Chest Pain and Diabetic Patients: Is There Benefit With Early Coronary CT Angiography? Results of the Randomized Comparative Effectiveness ROMICAT II Trial. J Am Heart Assoc. 2016 Mar 22;5(3):e003137. doi: 10.1161/JAHA.115.003137.

Pursnani A, Celeng C, Schlett CL, Mayrhofer T, Zakroysky P, Lee H, Ferencik M, Fleg JL, Bamberg F, Wiviott SD, Truong QA, Udelson JE, Nagurney JT, Hoffmann U. Use of Coronary Computed Tomographic Angiography Findings to Modify Statin and Aspirin Prescription in Patients With Acute Chest Pain. Am J Cardiol. 2016 Feb 1;117(3):319-24. doi: 10.1016/j.amjcard.2015.10.052. Epub 2015 Nov 18.

Ferencik M, Liu T, Mayrhofer T, Puchner SB, Lu MT, Maurovich-Horvat P, Pope JH, Truong QA, Udelson JE, Peacock WF, White CS, Woodard PK, Fleg JL, Nagurney JT, Januzzi JL, Hoffmann U. hs-Troponin I Followed by CT Angiography Improves Acute Coronary Syndrome Risk Stratification Accuracy and Work-Up in Acute Chest Pain Patients: Results From ROMICAT II Trial. JACC Cardiovasc Imaging. 2015 Nov;8(11):1272-1281. doi: 10.1016/j.jcmg.2015.06.016. Epub 2015 Oct 14.

Januzzi JL, Sharma U, Zakroysky P, Truong QA, Woodard PK, Pope JH, Hauser T, Mayrhofer T, Nagurney JT, Schoenfeld D, Peacock WF, Fleg JL, Wiviott S, Pang PS, Udelson J, Hoffmann U. Sensitive troponin assays in patients with suspected acute coronary syndrome: Results from the multicenter rule out myocardial infarction using computer assisted tomography II trial. Am Heart J. 2015 Apr;169(4):572-8.e1. doi: 10.1016/j.ahj.2014.12.023. Epub 2015 Jan 9.

Pursnani A, Chou ET, Zakroysky P, Deaño RC, Mamuya WS, Woodard PK, Nagurney JT, Fleg JL, Lee H, Schoenfeld D, Udelson JE, Hoffmann U, Truong QA. Use of coronary artery calcium scanning beyond coronary computed tomographic angiography in the emergency department evaluation for acute chest pain: the ROMICAT II trial. Circ Cardiovasc Imaging. 2015 Mar;8(3). pii: e002225. doi: 10.1161/CIRCIMAGING.114.002225. Epub 2015 Feb 20.

Puchner SB, Liu T, Mayrhofer T, Truong QA, Lee H, Fleg JL, Nagurney JT, Udelson JE, Hoffmann U, Ferencik M. High-risk plaque detected on coronary CT angiography predicts acute coronary syndromes independent of significant stenosis in acute chest pain: results from the ROMICAT-II trial. J Am Coll Cardiol. 2014 Aug 19;64(7):684-92. doi: 10.1016/j.jacc.2014.05.039.

Truong QA, Hayden D, Woodard PK, Kirby R, Chou ET, Nagurney JT, Wiviott SD, Fleg JL, Schoenfeld DA, Udelson JE, Hoffmann U. Sex differences in the effectiveness of early coronary computed tomographic angiography compared with standard emergency department evaluation for acute chest pain: the rule-out myocardial infarction with Computer-Assisted Tomography (ROMICAT)-II Trial. Circulation. 2013 Jun 25;127(25):2494-502. doi: 10.1161/CIRCULATIONAHA.113.001736. Epub 2013 May 17.

Hoffmann U, Truong QA, Schoenfeld DA, Chou ET, Woodard PK, Nagurney JT, Pope JH, Hauser TH, White CS, Weiner SG, Kalanjian S, Mullins ME, Mikati I, Peacock WF, Zakroysky P, Hayden D, Goehler A, Lee H, Gazelle GS, Wiviott SD, Fleg JL, Udelson JE; ROMICAT-II Investigators. Coronary CT angiography versus standard evaluation in acute chest pain. N Engl J Med. 2012 Jul 26;367(4):299-308. doi: 10.1056/NEJMoa1201161.

Hoffmann U, Truong QA, Fleg JL, Goehler A, Gazelle S, Wiviott S, Lee H, Udelson JE, Schoenfeld D; ROMICAT II. Design of the Rule Out Myocardial Ischemia/Infarction Using Computer Assisted Tomography: a multicenter randomized comparative effectiveness trial of cardiac computed tomography versus alternative triage strategies in patients with acute chest pain in the emergency department. Am Heart J. 2012 Mar;163(3):330-8, 338.e1. doi: 10.1016/j.ahj.2012.01.028. Epub 2012 Feb 22.

• Responsible Party: Udo Hoffmann, MD MPH, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01084239
• Other Study ID Numbers: 2009P002331
• First Submitted: January 7, 2010
• First Posted: March 10, 2010
• Results First Submitted: September 9, 2013
• Results First Posted: May 7, 2014
• Last Update Posted: May 7, 2014