Arm Exercise Versus Pharmacologic Stress Testing for Clinical Outcome

NCT ID: NCT03449888

Last Updated: 2022-02-17

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 133 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-07-01
• Study Completion Date: 2021-02-05

Brief Summary

This is a 5-year clinical trial to evaluate whether arm exercise electrocardiographic (ECG) stress testing without or with coronary artery calcium scoring (-/+ CAC) is non-inferior to treadmill ECG stress testing -/+ CAC and pharmacologic myocardial perfusion imaging as an initial evaluation to detect obstructive coronary artery disease, determined by cardiac computed tomographic angiography (CTA) and to predict clinical outcome, defined by a primary clinical endpoint of the composite of cardiovascular (CV) mortality, myocardial infarction, and 90-day post-stress test coronary artery revascularization and secondary clinical endpoints of all-cause mortality and CV mortality.

Detailed Description

Note: Recruitment is temporarily suspended because of VA-ORD moratorium due to Covid-19 pandemic. 04/01/2020

Treadmill exercise capacity and other physiologic responses to leg exercise are powerful predictors of mortality and provide important clinical and diagnostic information. However, many Veterans cannot perform treadmill exercise because of lower extremity or other disabilities. For many years, pharmacologic myocardial perfusion imaging (MPI) has been the standard of care for their evaluation but fails to provide powerful prognostic and clinically relevant information of exercise testing, requires exposure to ionizing radiation, and is several times more expensive than exercise electrocardiography (ECG). With a recently completed Merit Review award, we obtained substantial retrospective observational evidence that arm exercise ECG stress testing scores are at least equivalent to pharmacologic MPI for robust prediction of mortality and other measures of clinical outcome in Veterans who cannot perform leg exercise. Major hypotheses for the current proposal are: 1) arm exercise ECG stress testing scores or best fit models without or with coronary artery calcium scoring (-/+ CACS) are non-inferior to the Duke Treadmill Score -/+ CACS, best fit model treadmill ECG and regadenoson (r) MPI stress testing, all performed in the same Veterans in randomized order, as an initial evaluation for obstructive coronary artery disease (oCAD), and 2) arm exercise ECG stress testing scores or best fit models -/+ CACS are non-inferior to the Duke Treadmill Score -/+ CACS, best fit model treadmill ECG and rMPI stress testing in the same Veterans for predicting the primary clinical endpoint (composite of cardiovascular (CV) mortality, myocardial infarction, or 90-day post-stress test coronary revascularization) and secondary clinical endpoints of all-cause mortality and CV mortality. Our specific aim for all Veterans referred to the St. Louis Veterans Administration (VA) stress testing laboratory and are without exclusions for exercise or regadenoson stress testing or cardiac computed tomographic angiography (CTA), is to perform a single site prospective clinical trial comparing arm exercise ECG stress test scores and best models -/+ CACS with the Duke Treadmill Score -/+ CACS if able to perform treadmill exercise, and best fit treadmill ECG and rMPI models, all performed in the same Veterans, for identification of the diagnostic endpoint of oCAD, defined as a severely ( 70%) occluded epicardial, graft, or 50% left main coronary artery lumen, determined by cardiac CTA or invasive coronary arteriography, and prediction of the primary and secondary clinical endpoints described above. The arm exercise scoring system to be evaluated incorporates the variables arm exercise capacity in resting metabolic equivalents, 1-minute heart rate recovery and arm exercise-induced ST depression of 1 mm or greater. Regadenoson MPI variables to be evaluated include an abnormal MPI study and best fit models of summed stress and difference scores, transient ischemic dilatation, gated left ventricular ejection fraction, and the heart rate response. We plan to enroll 75 Veterans per year for 4 years and follow the entire cohort for an additional year. Statistical analyses will be performed with SAS using univariate and multivariate logistic and Cox regression models. We will evaluate non-inferiority of arm exercise scores -/+ CACS for their association with oCAD and prediction of clinical endpoints with a non-inferiority margin of 0.05. A long term goal is to develop a multi-site prospective randomized VA Cooperative Study to assess generalizability of arm exercise ECG stress testing -/+ CACS for diagnostic and prognostic evaluation in the VA and United States healthcare systems.

Conditions

Veterans Referred to the St. Louis VAMC Stress Tes

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

St. Louis VA Healthcare System stress testing referrals

St. Louis VA Healthcare System cardiac stress testing laboratory referrals who are eligible and willing to complete an arm exercise ECG stress test, a treadmill ECG stress test if able, a regadenoson myocardial perfusion imaging stress test, and a coronary artery calcium score and cardiac computed tomographic angiography evaluation within 60 days if not referred for invasive coronary arteriography.

Regadenoson myocardial perfusion imaging stress test

Intervention Type: PROCEDURE

Best fit model of pharmacologic myocardial perfusion imaging data, including summed stress and difference scores, gated left ventricular ejection fraction, transient ischemic dilatation, and heart rate response to regadenoson data.

Arm exercise electrocardiographic stress test

Intervention Type: PROCEDURE

Published arm exercise score and best fit model of arm exercise ECG stress testing data.

Treadmill electrocardiographic stress test

Intervention Type: PROCEDURE

Duke Treadmill Score and best fit model of treadmill exercise ECG stress testing data.

Coronary artery calcium score and cardiac computed tomographic angiography

Intervention Type: PROCEDURE

Coronary artery calcium score by Agatston criteria and severe obstructive coronary artery disease \> 70% by cardiac computed tomographic angiography or invasive coronary arteriography.

Interventions

Regadenoson myocardial perfusion imaging stress test

Best fit model of pharmacologic myocardial perfusion imaging data, including summed stress and difference scores, gated left ventricular ejection fraction, transient ischemic dilatation, and heart rate response to regadenoson data.

Intervention Type: PROCEDURE

Arm exercise electrocardiographic stress test

Published arm exercise score and best fit model of arm exercise ECG stress testing data.

Intervention Type: PROCEDURE

Treadmill electrocardiographic stress test

Duke Treadmill Score and best fit model of treadmill exercise ECG stress testing data.

Intervention Type: PROCEDURE

Coronary artery calcium score and cardiac computed tomographic angiography

Coronary artery calcium score by Agatston criteria and severe obstructive coronary artery disease \> 70% by cardiac computed tomographic angiography or invasive coronary arteriography.

Intervention Type: PROCEDURE

Other Intervention Names

Lexiscan; Arm exercise ECG; Treadmill ECG; Coronary calcium score and cardiac CTA

Eligibility Criteria

Inclusion Criteria

• Any veteran referred to the St. Louis VA Healthcare System stress testing laboratory for a cardiac stress test

Exclusion Criteria

• Contra-indications to stress testing such as acute coronary syndrome, uncompensated heart failure, or unstable cardiac dysrhythmias Inability to perform arm exercise stress testing
• Contra-indications to regadenoson stress testing such as significant reversible airway disease, heart block, or low blood pressure
• An abnormal baseline ECG (e.g. left bundle branch block, widespread ST segment depression of at least 1 mm, ventricular paced rhythm) that precludes interpretation of the stress ECG
• Contra-indications to cardiac computed tomographic angiography (CTA) such as contrast allergies and renal dysfunction (glomerular filtration rate < 30 ml/min)

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA St. Louis Health Care System

FED

Sponsor Role: collaborator

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wade H. Martin, MD

Role: PRINCIPAL_INVESTIGATOR

St. Louis VA Medical Center John Cochran Division, St. Louis, MO

Locations

St. Louis VA Medical Center John Cochran Division, St. Louis, MO

St Louis, Missouri, United States

Countries

United States

Other Identifiers

1 101 CX001345-01A3

Identifier Type: OTHER

Identifier Source: secondary_id

CARA-008-17F

Identifier Type: -

Identifier Source: org_study_id