Early Dronedarone Versus Usual Care to Improve Outcomes in Persons With Newly Diagnosed Atrial Fibrillation
- Registration Number
- NCT05130268
- Lead Sponsor
- American Heart Association
- Brief Summary
While there are several completed clinical trials that address treatment strategy in patients with symptomatic and recurrent AF, there are no randomized clinical trials that address treatment for first-detected AF. In usual care, these patients are started on an atrioventricular nodal blocking agent (beta-blocker or non-dihydropyridine calcium channel blocker) along with stroke prevention therapy. The investigators hypothesize that earlier administration of a well-tolerated antiarrhythmic drug proven to reduce hospitalization may result in improved cardiovascular outcomes and quality of life in patients first-detected AF.
The purpose of this study is to determine if treatment with dronedarone on top of usual care is superior to usual care alone for the prevention of cardiovascular hospitalization or death from any cause in patients hospitalized with first-detected AF. All patients will be treated with guideline-recommended stroke prevention therapy according to the CHA2DS2-VASc score. The treatment follow-up period will be 12 months. There will be two follow-up visits. Consistent with the pragmatic nature of the trial, the first follow-up will occur between 3 -9 months and the 2nd will occur at 12 months (with a window of +/- 30 days). Approximately 3000 patients will be enrolled and randomly assigned (1:1) to study intervention. The study intervention will be dronedarone 400 mg twice daily in addition to usual care versus usual care alone.
- Detailed Description
Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice, accounting for one-third of arrhythmia-related hospitalizations.1 As many as 1 in 4 people develop AF over their lifetime after the age of 40 years. The prevalence and burden of AF in the United States is substantial; the age-adjusted incidence and prevalence has increased over the last 3 decades. Moreover, the number of Americans with AF is expected to increase 150% by 2050. The goals of care in the treatment of AF include (1) the management and reduction of risk factors, (2) prevention of tachycardia (rate control), (3) prevention of stroke, and (4) improvement of symptoms. Reduction or elimination of symptoms often requires rhythm control. Historically, randomized clinical trials have not demonstrated a mortality or stroke benefit with a rhythm control versus a rate control strategy.
Despite the failure of prior randomized clinical trials to demonstrate the superiority of rhythm control, the recent Early Treatment of Atrial Fibrillation for Stroke Prevention 4 (EAST-AFNET 4) trial demonstrated that early introduction of a comprehensive rhythm-control strategy (within one year of diagnosis) is superior to guideline-based usual care in improving cardiovascular (CV) outcomes at a mean follow-up of 5 years. The EAST-AFNET 4 trial found that early rhythm control reduced the primary outcome of CV death, stroke, hospitalization for heart failure (HF), or acute coronary syndrome (HR 0.79, 96% confidence interval (CI) 0.66-0.94, p = 0.005). EAST-AFNET 4 also demonstrated a reduction in the risk of stroke with early introduction of rhythm control (HR 0.65, 95% CI 0.44-0.98), a finding that was also observed with dronedarone in the ATHENA trial. In addition, maintenance of sinus rhythm has been associated with improved quality of life and increased exercise capacity in some patients. Outside of clinical trials, a quality-of-life study from the Registry on Cardiac Rhythm Disorders Assessing the Control of Atrial Fibrillation (RECORD-AF) found that rhythm control was associated with better quality of life.
There are several antiarrhythmic drugs (AADs) available for rhythm control of AF. Class I antiarrhythmic agents are predominantly limited to younger patients without coronary artery or structural heart disease. Patients with advanced chronic kidney disease, prolonged QT intervals, and/or severe left ventricular hypertrophy should not be treated with sotalol or dofetilide. Even when sotalol or dofetilide can be used, patients are often hesitant to start a medication that requires an inpatient hospitalization for drug loading and laboratory evaluation every 3 months. Amiodarone has been shown to be the most effective AAD for maintaining sinus rhythm in patients with AF; however, based on its side effect profile, amiodarone is only recommended as a first-line agent under specific clinical circumstances. Moreover, despite its efficacy, amiodarone has high rates of discontinuation due to frequent adverse events. In addition to its unfavorable side effects, several studies, including those of patients at risk for sudden cardiac death, have demonstrated an association between amiodarone use and higher mortality, as well as lower functional status. In contrast to amiodarone, dronedarone is a much better tolerated antiarrhythmic medication. In randomized controlled trials, dronedarone has been shown to prevent recurrent AF, improve rate control, and decrease cardiovascular hospitalization in patients with AF.
While there are several completed clinical trials that address treatment strategy in patients with symptomatic and recurrent AF, there are no randomized clinical trials that address treatment for first-detected or new-onset AF. After appropriate evaluation for oral anticoagulation, these patients are often started on an atrioventricular nodal blocking agent (beta-blocker or non-dihydropyridine calcium channel blocker). The investigators hypothesize that earlier administration of a well-tolerated antiarrhythmic drug proven to reduce hospitalization may result in improved quality of life and cardiovascular outcomes in patients with first-detected AF.
Risk Assessment:
Dronedarone is approved by the Food and Drug Administration to reduce the risk of hospitalization for AF in patients with paroxysmal or persistent AF. The efficacy and safety of dronedarone 400 mg twice daily was evaluated in five controlled studies, ATHENA, ANDROMEDA, European Trial in Atrial Fibrillation or Flutter Patients Receiving Dronedarone for the Maintenance of Sinus Rhythm (EURIDIS), ADONIS, and Dronedarone Atrial FibrillatioN study after Electrical Cardioversion (DAFNE), involving more than 6,000 patients with including more than 3200 patients who received dronedarone. As with any therapeutic agent, there are known risks with dronedarone therapy. These risks include hepatic injury, heart failure exacerbation, increased exposure to digoxin, increased plasma concentration of tacrolimus, sirolimus, and other Cytochrome P450, family 3, subfamily A (CYP 3A) substrates, and very rare instances of pulmonary toxicity. The risks of dronedarone are felt to be outweighed by its benefits. The guideline recommendations provided by the European Society of Cardiology and American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Rhythm Society (HRS) are commensurate with this risk benefit assessment.
Benefit Assessment:
While there are no completed randomized clinical trials to guide selection or initiation of rhythm control therapies in patients with first-detected AF, there are recent trials that suggest benefit with both dronedarone antiarrhythmic therapy and early-initiation of rhythm control in persons with AF. the recent EAST-AFNET 4 trial demonstrated that early introduction of a comprehensive rhythm-control strategy (within one year of diagnosis) is superior to usual guideline-recommended care in improving cardiovascular (CV) outcomes at 5 years. The median time from new-onset AF to randomization in the EAST-AFNET4 trial was 36 days. The trial found that early rhythm control reduced the primary outcome of CV death, stroke, hospitalization for HF, or acute coronary syndrome (HR 0.79, 95% confidence interval 0.66-0.94, p = 0.005). EAST-AFNET 4 also demonstrated a reduction in the risk of stroke with early introduction of rhythm control (HR 0.65, 95% CI 0.44-0.98), a finding that was also observed with dronedarone in the ATHENA trial. Thus, the investigators hypothesize that early initiation of dronedarone in patients with new-onset AF will lead to a reduction in CV hospitalization or death.
Overall Design:
Dronedarone is approved by the Food and Drug Administration to reduce the risk of CV hospitalization in patients with AF or atrial flutter. However, it is unknown if dronedarone (or any antiarrhythmic medication) can reduce CV hospitalization or death in patients with first-detected AF. This trial has been designed to address this important question. In order to facilitate the trial enrollment, data collection, and a generalizability to clinical practice, the CHANGE AFIB study has been designed as an open-label pragmatic clinical trial nested within the Get With The Guidelines (GWTG) Atrial Fibrillation registry. At present the overall GWTG program is being implemented in over 2,300 hospitals across the U.S. and is comprised of over 9 million patient records, with an estimated 650,000 new patient records entered per year. The trial will utilize the existing GWTG registry network, data collection architecture, and experience to facilitate both enrollment and conduct of the trial.
The comparator arm will be "usual care." Thus, this study will compare usual care plus dronedarone versus usual care alone. In most patients, the investigators anticipate usual care to include an atrioventricular nodal blocking agent (beta-blocker, non-dihydropyridine calcium channel blocker, or digoxin) without an antiarrhythmic. As dronedarone has anti-adrenergic rate controlling properties, a low dose of beta-blocker or calcium-channel blocker is recommended in the USPI when starting dronedarone. In the dronedarone arm concomitant digoxin use will be contraindicated due to P-gp interaction based upon data from the PALLAS trial. All patients will receive oral anticoagulation for stroke prevention according to current guideline recommendations.
CHANGE AFIB will leverage several critical advantages as a pragmatic clinical trial. Data collection will be integrated into the Get With The Guidelines AFIB registry. The use of the GWTG-AFIB registry will also enhance subject recruitment and ensure the enrollment of a diverse group of patients. The randomized intervention will be compared with usual care thus further enhancing generalizability. Follow-up visits will be minimized to reduce patient burden. Moreover, follow-up visits will have "windows" to accommodate variation in follow-up intervals at different centers.
Justification for Study Drug Intervention and Dose:
Dronedarone is a non-iodinated benzofuran similar to amiodarone but is not associated with thyroid or pulmonary toxicity in randomized clinical trials or post-marketing observational studies. Dronedarone has electrophysiological characteristics spanning all 4 Vaughan-Williams anti-arrhythmic classes, with primarily class III effects. Initial trials suggested that dronedarone prolonged the time to recurrence of AF and reduced cardiovascular death and hospitalization.
The landmark ATHENA trial evaluated the efficacy and safety of dronedarone in patients with atrial arrhythmias (atrial fibrillation or atrial flutter). This trial did not include patients with a recent history of New York Heart Association (NYHA) class IV heart failure or recent hospitalization for decompensated heart failure (\<4 weeks). Approximately, 30% of the ATHENA population had NYHA class I-III heart failure. ATHENA demonstrated that dronedarone 400 mg twice daily (in combination with background therapy) reduced the combined endpoint of CV hospitalization or death from any cause by 24% (p\<0.001) compared with placebo. Of course, the ATHENA trial was not conducted in the special population of patients with a new diagnosis of AF. There are no randomized trials or guideline recommendations for antiarrhythmic therapy at the time of first-detected AF. A subgroup analysis from the ATHENA trial suggests that optimal outcomes may be achieved in those patients with shorter duration of AF (time from diagnosis). Similar observations have also been made in patients undergoing other forms of rhythm control, including catheter ablation. In this trial, patients with first-detected AF will be randomized to dronedarone on top of usual care versus usual care alone. Patients randomized to the intervention arm will be prescribed and treated with Dronedarone 400 mg bid. This dose has been chosen as it is the Food and Drug Administration approved dose as well as the dose recommended in current international guidelines. Dronedarone has also been shown to be an effective rate control agent as well. In the ERATO study treatment with dronedarone 400 mg twice daily let to a mean reduction of 24.5 beat/min in patients with permanent AF when compared with placebo. In the EURIDIS/ADONIS studies the mean difference in patients with paroxysmal/persistent AF during AF recurrence was 14 beats/min. Moreover, the dronedarone treated patients experienced improved rate control without any reduction in exercise tolerance as measured by maximal exercise.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 339
- Age >=21 years.
- First-detected atrial fibrillation (defined as atrial fibrillation diagnosed in the previous 120 days).
- Electrocardiographic documentation of atrial fibrillation.
- Estimated life expectancy of at least 1 year.
- Patient or legal authorized representative capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
-
Patients with prior or planned treatment with rhythm control, either catheter ablation or chronic (>7 days) antiarrhythmic drug therapy.
-
Planned cardiothoracic surgery. 4. New York Heart Association class III or IV heart failure or a hospitalization for heart failure in the last 4 weeks.
-
Patients with reduced ejection fraction (LVEF ≤40%). 6. Permanent atrial fibrillation. 7. Ineligible for oral anticoagulation, unless CHA2DS2-VASc is less than 3 in women or 2 in men.
-
Bradycardia with a resting heart rate < 50 bpm 9. PR interval >280 msec or 2nd degree or 3rd degree atrioventricular block without a permanent pacemaker/cardiac implanted electronic device.
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Corrected QT interval >=500 msec. 11. Pregnancy or breast feeding. 12. Severe hepatic impairment in the opinion of the investigator.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dronedarone Dronedarone In most patients, the investigators anticipate usual care to include an atrioventricular nodal blocking agent (beta-blocker, non-dihydropyridine calcium channel blocker, or digoxin) without an antiarrhythmic. As dronedarone has anti-adrenergic rate controlling properties, a low dose of beta-blocker or calcium-channel blocker is recommended in the United States Prescribing Information (USPI) when starting dronedarone. In the dronedarone arm concomitant digoxin use will be contraindicated due to P-gp interaction based upon data from the PALLAS trial. All patients will receive oral anticoagulation for stroke prevention according to current guideline recommendations.
- Primary Outcome Measures
Name Time Method Cardiovascular Hospitalization or Death Evaluated through 12 months from randomization First occurrence of unplanned CV hospitalization or death from any cause within 12 months of randomization. All unplanned hospitalizations (i.e. admission with an overnight stay in an acute care healthcare facility/hospital) for cardiovascular causes will be considered a cardiovascular hospitalization.
- Secondary Outcome Measures
Name Time Method Hospitalization for acute coronary syndrome Evaluated through 12 months from randomization Any hospitalization (i.e. admission with an overnight stay in an acute care healthcare facility/hospital) due to acute coronary syndrome.
Ischemic stroke or systemic embolism Evaluated through 12 months from randomization The occurrence of ischemic stroke will be defined as an acute episode of focal or global neurological dysfunction caused by brain, spinal cord, or retinal vascular injury as a result of hemorrhage or infarction. Symptoms or signs must persist ≥24 hours, unless the stroke is documented by CT, MRI or autopsy, in which case the duration of symptoms/signs may be less than 24 hours. Stroke may be classified as ischemic (including hemorrhagic transformation of ischemic stroke), hemorrhagic, or undetermined. Systemic embolism will be defined as acute arterial insufficiency or occlusion of the extremities or any non-CNS organ associated with clinical, imaging, surgical/autopsy evidence of arterial occlusion in the absence of other likely mechanism (e.g., trauma, atherosclerosis, or instrumentation).
Hospitalization for new/worsening diagnosis of heart failure Evaluated through 12 months from randomization Hospitalization for new or worsening heart failure will be defined as any unplanned hospitalization (i.e. admission with an overnight stay in an acute care healthcare facility/hospital) due to a new diagnosis or worsening symptomatic heart failure
Time to first unplanned cardiovascular hospitalization Evaluated through 12 months from randomization Given the importance of CV hospitalization as an outcome from a clinical perspective, patient perspective, and economic perspective, there will be two analyses of CV hospitalization. The key secondary endpoint will be time to first unplanned CV hospitalization (similar to the component of the primary endpoint).
Unplanned cardiovascular hospitalizations--secondary analysis using Anderson-Gill extension Evaluated through 12 months from randomization Given the importance of CV hospitalization as an outcome from a clinical perspective, patient perspective, and economic perspective, there will be two analyses of CV hospitalization. The second exploratory analysis of unplanned cardiovascular hospitalization will use a method to account for repeated events (Anderson-Gill extension).
Win Ratio Evaluated through 12 months from randomization Among the randomized patients, every patient in the dronedarone arm will be compared with every patient in the usual care arm. Within each pair of patients, the component outcomes will be compared in descending order of importance until one of the patients in the pair demonstrates a better outcome compared with the other. For the purpose of this trial the hierarchy of component outcomes are shown below. The components in the WIN ratio hierarchy are similar to the endpoints considered in the recent EAST AFNET4 trial.
Hierarchy of Outcomes for the WIN Ratio:
1. All-cause mortality
2. Ischemic stroke or systemic embolism
3. Hospitalization for new/worsening diagnosis of heart failure
4. Hospitalization for acute coronary syndromeAll-cause mortality Evaluated through 12 months from randomization For descriptive purposes, deaths will be categorized by the site investigators according to the following categories: cardiovascular and non-cardiovascular. Cardiovascular deaths will be further classified into arrhythmic vs non-arrhythmic according the modified Hinkle-Thaler criteria, as used in several landmark cardiovascular trials. Patients who are well and (1) have a witnessed sudden collapse or (2) those found dead, but known to be alive and well in the previous 24 hours (e.g. no signs or symptoms of cardiorespiratory distress) will be defined as having arrhythmic death.
Trial Locations
- Locations (102)
The MetroHealth System
🇺🇸Cleveland, Ohio, United States
Golden Touch Clinical Research
🇺🇸Miami, Florida, United States
The Miami Research Group
🇺🇸Miami, Florida, United States
Los Angeles Medical Center (Kaiser Permenente)
🇺🇸Los Angeles, California, United States
UC Irvine Medical Center (AKA UCI Health)
🇺🇸Orange, California, United States
Los Robles Health System - Los Robles Regional Medical Center
🇺🇸Thousand Oaks, California, United States
UCLA Medical Center - Harbor
🇺🇸Torrance, California, United States
University of Illinois Hospital
🇺🇸Chicago, Illinois, United States
First Coast Cardiovascular Institute
🇺🇸Jacksonville, Florida, United States
Life Spring Research Foundation, LLC
🇺🇸Miami, Florida, United States
Enmanuel Advanced Research Center, LLC
🇺🇸Miami, Florida, United States
Excellence Medical And Research, LLC
🇺🇸Miami, Florida, United States
Parkview Hospital, Inc.
🇺🇸Fort Wayne, Indiana, United States
Nouvelle Clinical Research LLC
🇺🇸Miami, Florida, United States
Wellstar Kennestone Hospital
🇺🇸Marietta, Georgia, United States
Northside Hospital
🇺🇸Saint Petersburg, Florida, United States
Georgia Arrhythmia Consultants and Research Institute
🇺🇸Macon, Georgia, United States
Marshfield Medical Center
🇺🇸Weston, Wisconsin, United States
Mayo Clinic Hospital - Franciscan Healthcare La Crosse
🇺🇸La Crosse, Wisconsin, United States
Duke University Hospital
🇺🇸Durham, North Carolina, United States
Ascension Saint Thomas Midtown
🇺🇸Nashville, Tennessee, United States
Kansas City Heart and Vascular Specialists at Providence Medical Center
🇺🇸Kansas City, Kansas, United States
Overland Park Regional Medical Center
🇺🇸Overland Park, Kansas, United States
Christiana Hospital
🇺🇸Newark, Delaware, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Mercy Gilbert Medical Center
🇺🇸Gilbert, Arizona, United States
HonorHealth Scottsdale Shea Medical Center
🇺🇸Scottsdale, Arizona, United States
Thomas Hospital
🇺🇸Fairhope, Alabama, United States
West Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Colorado Heart & Vascular Group - St. Anthony's Hospital
🇺🇸Lakewood, Colorado, United States
The Angel Medical Research
🇺🇸Miami Lakes, Florida, United States
Northeast Georgia Medical Center
🇺🇸Gainesville, Georgia, United States
Mt Sinai Hospital Medical Center
🇺🇸Chicago, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Riverside Medical Center
🇺🇸Kankakee, Illinois, United States
Proctor Community Hospital
🇺🇸Peoria, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Captain James A Lovell Federal Health Care Center
🇺🇸North Chicago, Illinois, United States
Trinity Rock Island
🇺🇸Rock Island, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
St. Elizabeth's Hospital of the Hospital Sisters of the Third Order of St. Francis
🇺🇸Springfield, Illinois, United States
St. John's Hospital of the Hospital Sisters of the Third Order of St. Francis
🇺🇸Springfield, Illinois, United States
Carle Foundation Hospital
🇺🇸Urbana, Illinois, United States
Ascension St Vincent Hospital - Indianapolis
🇺🇸Indianapolis, Indiana, United States
Heart Clinic of Hammond
🇺🇸Hammond, Louisiana, United States
Saint Agnes Hospital
🇺🇸Baltimore, Maryland, United States
Luminis Health Anne Arundel Medical Center
🇺🇸Annapolis, Maryland, United States
Adventist Healthcare Shady Grove Medical Center
🇺🇸Rockville, Maryland, United States
McLaren Bay Region
🇺🇸Bay City, Michigan, United States
Brigham and Womens Hospital
🇺🇸Boston, Massachusetts, United States
DMC Harper University Hospital (AKA Wayne State University Hospital)
🇺🇸Detroit, Michigan, United States
Sparrow Hospital
🇺🇸Lansing, Michigan, United States
McLaren Macomb
🇺🇸Mount Clemens, Michigan, United States
Trinity Health Ann Arbor Hospital - Michigan Heart
🇺🇸Ypsilanti, Michigan, United States
Minneapolis VA Health Care System
🇺🇸Minneapolis, Minnesota, United States
University Hospital - University of Missouri
🇺🇸Columbia, Missouri, United States
SSM Health Saint Louis University Hospital
🇺🇸Saint Louis, Missouri, United States
Barnes-Jewish Hospital (AKA Washington Univ)
🇺🇸Saint Louis, Missouri, United States
The Valley Hospital
🇺🇸Ridgewood, New Jersey, United States
Albany Medical Center
🇺🇸Albany, New York, United States
NewYork-Presbyterian/Columbia University Irving Medical Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering
🇺🇸New York, New York, United States
DiGiovanna Institute for Medical Education & Research
🇺🇸North Massapequa, New York, United States
Durham VA Health Care System
🇺🇸Durham, North Carolina, United States
WakeMed Raleigh Campus
🇺🇸Raleigh, North Carolina, United States
Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
Kettering Medical Center
🇺🇸Kettering, Ohio, United States
Kettering Health Dayton
🇺🇸Dayton, Ohio, United States
McLaren - St Lukes Hospital
🇺🇸Maumee, Ohio, United States
Wooster Community Hospital Health System
🇺🇸Wooster, Ohio, United States
Oklahoma City VA Health Care System
🇺🇸Oklahoma City, Oklahoma, United States
Penn State Health Holy Spirit Medical Center
🇺🇸Camp Hill, Pennsylvania, United States
Penn State Health Milton S Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Penn State Health St Joseph Medical Center - Main Campus
🇺🇸Reading, Pennsylvania, United States
Texas Health Fort Worth (FKA Texas Health Harris Methodist Hospital Fort Worth)
🇺🇸Fort Worth, Texas, United States
Synapse Clinical Research
🇺🇸Missouri City, Texas, United States
University of Utah Hospital
🇺🇸Salt Lake City, Utah, United States
JW Ruby Memorial Hospital
🇺🇸Morgantown, West Virginia, United States
University Hospital at University of Texas San Antonio
🇺🇸San Antonio, Texas, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
Pharma Medical Innovations
🇺🇸Miami Lakes, Florida, United States
Memorial Hermann - Texas Medical Center
🇺🇸Houston, Texas, United States
Trinity Hospital
🇺🇸Minot, North Dakota, United States
Texas Institute of Cardiology
🇺🇸McKinney, Texas, United States
Ocean Wellness Center, LLC
🇺🇸Miami Gardens, Florida, United States
Cooper University Hospital
🇺🇸Camden, New Jersey, United States
Colorado Heart & Vascular Group - St. Anthony's North Health Campus
🇺🇸Westminster, Colorado, United States
New Hanover Regional Medical Center
🇺🇸Wilmington, North Carolina, United States
Guardian Angel Research Center
🇺🇸Tampa, Florida, United States
CHI Health Creighton University Medical Center - Bergan Mercy
🇺🇸Omaha, Nebraska, United States
NYC Health and Hospitals - Lincoln
🇺🇸Bronx, New York, United States
NYC Health and Hospitals - Jacobi
🇺🇸Bronx, New York, United States
NYC Health and Hospitals - North Central Bronx
🇺🇸Bronx, New York, United States
Chippenham and Johnston Willis Medical Center
🇺🇸Richmond, Virginia, United States
Hunter Holmes McGuire VA Medical Center (AKA Richmond VA Medical Center)
🇺🇸Richmond, Virginia, United States
Tulane Medical Center
🇺🇸New Orleans, Louisiana, United States
Ascension Seton Medical Center Austin
🇺🇸Austin, Texas, United States
Baptist Health Lexington
🇺🇸Lexington, Kentucky, United States
Saint Joseph Hospital
🇺🇸Lexington, Kentucky, United States
University Hospital - University of Wisconsin-Madison
🇺🇸Madison, Wisconsin, United States
UW Health at the American Center (AKA UW Health East Madison Hospital)
🇺🇸Madison, Wisconsin, United States