Randomized Placebo-controlled Trial of FCM as Treatment for Heart Failure With Iron Deficiency

Heart Failure Clinical Trial

— HEART-FID  

Official title:

A Randomized, Double-Blind, Placebo- Controlled Study to Investigate the Efficacy and Safety of Injectafer® (Ferric Carboxymaltose) as Treatment for Heart Failure With Iron Deficiency

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03037931
• Other study ID #: 1VIT15043
• Status: Completed
• Phase: Phase 3
• Start date: March 15, 2017
• Est. completion date: February 2, 2023

Study information

• Verified date: April 2023
• Source: American Regent, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to determine the efficacy and safety of iron therapy using intravenous (IV) ferric carboxymaltose (FCM), relative to placebo in the treatment of participants in heart failure with a reduced ejection fraction and with iron deficiency

Description:

This is a double-blind, multicenter, prospective, randomized, placebo-controlled study to assess the effects of IV FCM compared to placebo on the 12-month rate of death, hospitalization for worsening heart failure, and the 6-month change in 6 minute walk test (6MWT) distance for patients in heart failure with iron deficiency.

After an initial screening period of up to 28 days, eligible participants will be stratified by region and randomized in a 1:1 ratio to FCM or placebo for treatment.

Study drug administration will occur on Day 0 and Day 7 (±2) as an undiluted slow IV push, with additional study visits planned at 3 month intervals, and additional dosing administered every 6 months as applicable. In a subset of sites, a sub-study will be conducted to characterize serum phosphate levels over time in participants with heart failure and iron deficiency after dosing with FCM. For all participants, hematology, ferritin, and transferrin saturation (TSAT), with appropriate safety evaluations, to determine additional treatment, will occur at 6 month intervals.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3065
• Est. completion date: February 2, 2023
• Est. primary completion date: February 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adult (=18 years of age) able to provide signed, written informed consent.

2. Stable heart failure (NYHA II-IV) on maximally-tolerated background therapy (as determined by the site Principle Investigator) for at least 2 weeks prior to randomization.

3. Able and willing to perform a 6MWT at the time of randomization.

4. Reduced left ventricular ejection fraction. Assessment must be performed at least 12 weeks after major cardiac surgical intervention including coronary artery bypass graft (CABG), valvular repair/replacement, or cardiac resynchronization therapy (CRT) device implantation.

a. Left ventricular ejection fraction = 40% obtained during the screening visit OR either of the following i. Historical value of ejection fraction = 40% within 24 months of screening visit ii. Historical value of ejection fraction = 30% within 36 months of screening visit

5. Hemoglobin >9.0 g/dL and < 13.5 g/dL (females) or <15.0 g/dL (males) within 28 days of randomization.

6. Serum ferritin <100 ng/mL or 100 to 300 ng/mL with TSAT <20%.Patients with screening ferritin <15 ng/mL must have documentation of an appropriate evaluation, as determined by the Principle Investigator, within 3 months of screening and prior to randomization.

7. Either documented hospitalization for heart failure within 12 months of enrollment or elavated N-terminal-pro-brain natriuretic peptide (NT-proBNP) within 90 days of randomization. a. For patients in normal sinus rhythm: N-terminal-pro-brain natriuretic peptide (NT- proBNP) > 600 pg/mL (or BNP >200 pg/mL) . b . For patients in atrial fibrillation: NT-proBNP >1000 pg/mL (or BNP >400 pg/mL) .

Exclusion Criteria:

1. Known hypersensitivity reaction to any component of FCM.

2. History of acquired iron overload, or the recent receipt (within 3 months) of erythropoietin stimulating agent, IV iron therapy, or blood transfusion.

3. Acute myocardial infarction, acute coronary syndrome, transient ischemic attack, or stroke within 30 days of enrollment.

4. Uncorrected severe aortic stenosis, severe valvular regurgitation (except mitral regurgitation due to left ventricular dilatation without planned intervention), or left ventricular outflow obstruction requiring intervention.

5. Current atrial fibrillation or atrial flutter with a mean ventricular response rate >100 per minute (at rest).

6. Current or planned mechanical circulatory support or heart transplantation.

7. Hemodialysis or peritoneal dialysis (current or planned within the next 6 months).

8. Documented liver disease, or active hepatitis (i.e. alanine transaminase or aspartate transaminase >3 times the upper limit of normal range).

9. Current or recent (within 3 years) malignancy with exception of basal cell carcinoma or squamous cell carcinoma of the skin, or cervical intraepithelial neoplasia.

10. Active gastrointestinal bleeding.

11. Female participant of child-bearing potential who is pregnant, lactating, or not willing to use adequate contraceptive precautions during the study and for up to 5 days after the last scheduled dose of study medication.

12. Inability to return for follow up visits within the necessary windows

13. Concurrently in a study with investigational product.

14. No participants with Current COVID-19 Infection into the study.

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Heart Failure
• Iron-deficiency

Intervention

Drug:
• Ferric Carboxymaltose
Intravenous Iron
• Placebo
Normal Saline Solution

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	The Queen Elizabeth Hospital	Adelaide	South Australia
Australia	SA Heart	Ashford	South Australia
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Sunshine Coast University Hospital	Birtinya	Queensland
Australia	Cairns Hospital	Cairns	Queensland
Australia	The Prince Charles Hospital	Chermside	Queensland
Australia	Heart Lung Clinic	Darlinghurst	Sydney
Australia	Lyell McEwin Hospital	Elizabeth Vale	South Australia
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	SWSLHD-Liverpool Hospital	Liverpool	New South Wales
Australia	Macquarie University - Clinical Trials Unit	Macquarie Park
Australia	Core Research Group	Milton	Queensland
Australia	John Hunter Hospital	New Lambton Heights
Australia	Epworth HealthCare Clinical Trials	Richmond
Australia	Gold Coast University Hospital	Southport	Queensland
Bulgaria	MHAT Puls	Blagoevgrad
Bulgaria	Multiprofile Hospital for Active Treatment: Department of cardiology	Gabrovo
Bulgaria	MHAT Haskovo AD	Haskovo
Bulgaria	Diagnostic - Consultative Center 1 - Lom - EOOD Office of Cardiology	Lom
Bulgaria	Medical Center Medconsult Pleven OOD	Pleven
Bulgaria	?C Hipokrena	Sevlievo
Bulgaria	5th City Hospital	Sofia
Bulgaria	Diagnostic - Consultative Center XXII - Sofia EOOD, Office of Cardiology	Sofia
Bulgaria	Medical Center Hera EOOD - Office of Cardiology	Sofia
Bulgaria	National Multiprofile Transport Hospital Cardiology Clinic	Sofia
Bulgaria	Second Medical Center-Sofia, EEOD - Department of Cardiology	Sofia
Bulgaria	Second Multiprofile Hospital for Active Treatment	Sofia
Bulgaria	Multiprofile Regional Hospital for Active Treatment	Veliko Tarnovo
Bulgaria	Medical Center Velingrad 2017" EOOD, Office of Cardiology	Velingrad
Canada	Manna Research Inc., Burlington South	Burlington	Ontario
Canada	University of Calbary	Calgary	Alberta
Canada	Cambridge Cardiac Care Center	Cambridge	Ontario
Canada	Vizel Cardiac Research	Cambridge	Ontario
Canada	Royal Alexandria Hospital	Edmonton	Alberta
Canada	South Edmonton Cardiology Consultants	Edmonton	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Nova Scotia Health Authority	Halifax	Nova Scotia
Canada	Clinique de Cardiologie de Lévis	Lévis	Quebec
Canada	London Health Sciences Center (LHSC)	London	Ontario
Canada	G.A. Research Associates, Ltd.	Moncton	New Brunswick
Canada	McGill University Health Centre (MUHC)	Montréal	Quebec
Canada	Montreal Heart Institute	Montréal	Quebec
Canada	Fraser Clinical Trials	New Westminster	British Columbia
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Quebec - Université Laval	Québec	Quebec
Canada	Health Sciences Centre	Saint John's	Newfoundland and Labrador
Canada	CISSS de Chaudière-Appalaches (CISSS-CA), site Hôpital St-Georges	Saint-Georges	Quebec
Canada	Recherche Medical St-Jerome Inc.	Saint-Jérôme	Quebec
Canada	Royal University Hospital	Saskatoon	Saskatchewan
Canada	SMH Cardiology Clinical Trials	Surrey	British Columbia
Canada	Sinai Health System - Mount Sinai Hospital	Toronto	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Centre Intégré Universitaire de Santé et de Services Sociaux de la Mauricie-et-du-centre-du-Quebec	Trois-Rivières	Quebec
Canada	St. Paul's Hospital	Vancouver	British Columbia
Canada	Victoria Heart Institute Foundation	Victoria	British Columbia
Czechia	Interni kardiologicka klinika FN Brno	Brno
Czechia	Kardiologicka ambulance	Chlumec Nad Cidlinou
Czechia	Centrum preventivní kardiologie	Prague
Czechia	Centrum preventivní kardiologie, Karlovo nám. 32,	Prague
Czechia	General University Hospital	Prague
Czechia	General University Hospital in Prague	Prague
Czechia	IKEM-Klinika kardiologie	Prague
Georgia	JSC Evex Hospitals,Georgia	Batumi
Georgia	Clinic-LJ	Kutaisi
Georgia	Acad. G. Chapidze Emergency Cardiology Center	Tbilisi
Georgia	Aleksandre Aladashvili Clinic LLC	Tbilisi
Georgia	Bokhua Memorial Cardiovascular Center	Tbilisi
Georgia	Georgian-Dutch Hospital	Tbilisi
Georgia	Ltd Israel-Georgian Medical Research Clinic "Helsicore"	Tbilisi
Georgia	Ltd Pineo Medical Ecosistem	Tbilisi
Georgia	Ltd TIM- Tbilisi Institute of Medicine	Tbilisi
Georgia	Tbilisi Heart and Vascular Clinic	Tbilisi
Hungary	Semmelweis Egyetem Városmajori Szív és- Érgyógyászati Klinika Szent Rókus Klinikai Tömb, Kardiológiai	Budapest
Hungary	Semmelweis Egyetem Városmajori Szív- és Érgyógyászati Klinika	Budapest
Hungary	Debreceni Egyetem Klinikai Központ Kardiológiai Osztály	Debrecen
Hungary	Clinexpert Gyöngyös Kft	Gyöngyös
Hungary	Zsigmondy Vilmos Harkányi Gyógyfürd? Kórház	Harkány
Hungary	Bács-Kiskun Megyei Kórház Kardiológiai Osztály	Kecskemet
Hungary	Andrea Hornyik, MD	Miskolc
Hungary	Pécsi Tudomány Egyetem Klinikai Központ, I. sz. Belgyógyászati Klinika,	Pecs
Hungary	Jász-Nagykun-Szolnok Megyei Hetény i Géza Kórház Kardiológiai Osztály	Szolnok
Hungary	Belvárosi Egészségház Kft	Zalaegerszeg
Latvia	Daugavpils Regional Hospital	Daugavpils
Latvia	Liepajas Regional Hospital	Liepaja
Latvia	Pauls Stradins Clinical University Hospital	Riga
Latvia	Riga East University hospital clinic Gailezers	Riga
Lithuania	The Hospital of Lithuanian	Kaunas
Lithuania	Klaipeda Seaman's Hospital	Klaipeda
Lithuania	Vilnius University Hospital Santaros Klinikos	Vilnius
New Zealand	Auckland City Hospital	Auckland
New Zealand	Middlemore Hospital	Auckland
New Zealand	North Shore Hospital	Auckland
New Zealand	Totara Clinical Research, Health New Lynn	Auckland
New Zealand	Christchurch Heart Institute	Christchurch
New Zealand	Dunedin Hospital	Dunedin
New Zealand	Hauora Tairawhiti Department of Cardiology	Gisborne
New Zealand	Hawke's Bay Hospital	Hastings
New Zealand	Hutt Hospital	Lower Hutt
New Zealand	Nelson Hospital	Nelson
New Zealand	Taranaki Base Hospital	New Plymouth
New Zealand	Wellington Hospital	Newton	Wellington
New Zealand	Rotorua Hospital	Rotorua
New Zealand	Clinical Horizons NEW ZEALAND LTD	Tauranga
Poland	Oddzial Kardiologii WSzS nr 4	Bytom
Poland	Biokinetica S.A. Przychodnia Józefów	Józefów
Poland	Centrum Medyczne Linden	Kraków
Poland	Marcin Ogórek, MD, PhD	Lódz
Poland	1 Wojskowy Szpital Klininiczny w Lublinie	Lublin
Poland	Ko-Med Centra Kliniczne	Lublin
Poland	Szpital Swietej Anny w Miechowie	Miechów
Poland	Szpital Swietej Anny w Miechowie	Miechów
Poland	Nowodworskie Centrum Medyczne. Ambulatoryjna Opieka Specjalistyczna	Nowy Dwór Mazowiecki
Poland	Zespol Opieki Zdrowotnej	Olawa
Poland	Wojewódzki Szpital Zespolony im. L. Rydygiera,Oddzialu Kardiologii i lntensywnej Terapii Kardiologicznej	Torun
Poland	Uniwersyteckie Centrum Kliniczne	Warszawa
Poland	Centrum Medyczne K2J2	Wolomin
Poland	4th Military Hospital	Wroclaw
Poland	Proximum Centrum Uslug Medycznych NZOZ	Wroclaw
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego	Wroclaw
Russian Federation	Municipal Autonomous Healthcare Institution	Chelyabinsk
Russian Federation	Municipal Autonomous Healthcare Institution "City Clinical Hospital #6	Chelyabinsk
Russian Federation	Federal State Budgetary Scientific Institution Research Institute for Complex Issues of Cardiovascular Diseases	Kemerovo
Russian Federation	State Budgetary Healthcare Institution of Moscow city "Moscow	Moscow
Russian Federation	Private Medical Institution "Euromedservice	Pushkin
Russian Federation	State Budgetary Institution of Ryazan Region	Ryazan
Russian Federation	JSC Polyclinic Complex	Saint Petersburg
Russian Federation	LLC "Scientific Research Center Eco-Safety"	Saint Petersburg
Russian Federation	Saint-Petersburg State Budgetary Institution of Healthcare "Saint Martyr Elizabeth city hospital"	Saint Petersburg
Russian Federation	JSC Polyclinic Complex	Saint-Petersburg
Russian Federation	Federal State Budget Educational Institution of Higher Education Saratov State Medical University of the Ministry of Health of Russia	Saratov
Russian Federation	State Healthcare Institution	Saratov
Russian Federation	LLC X7 Clinical Research	St. Petersburg
Russian Federation	Saint Petersburg Research Institute of Emergency Medicine	St. Petersburg
Russian Federation	Saint Petersburg Research Institute of Emergency Medicine n.a. I.I. Dzhanelidze	St. Petersburg
Ukraine	Municipal non-profit enterprise "Ivano-Frankivsk Regional Clinical Cardiological Center"	Ivano-Frankivs'k
Ukraine	Military and Medical Clinical Center of the Northern Region (Military Unit A-3306) Cardiology Department	Kharkiv
Ukraine	MNCE "City Hospital ? 8" of Kharkiv City Council, Cardiology Department ?2	Kharkiv
Ukraine	Scientific Medical Complex "University Clinic" of Kharkiv	Kharkiv
Ukraine	Communal Institution "Kryvyi Rih City Hospital ?9" of Kryvyi Rih City Council	Kryvyi Rih
Ukraine	Communal non-profit enterprise Kyiv City Clinical Hospital ?1	Kyiv
Ukraine	Communal nonprofit enterprise "Oleksandrivska Clinical Hospital of Kyiv	Kyiv
Ukraine	Kyiv City Clinical Hospital of Emergency Aid	Kyiv
Ukraine	Kyiv City Clinical Hospital of Emergency Aid,	Kyiv
Ukraine	Kyiv Clinic Railway Hospital ?2 of the "Health Care Center" Brach at the PJSC "Ukrainian Railway"	Kyiv
Ukraine	Medical Centre of LLC	Kyiv
Ukraine	Medical Centre of LLC "Medical Centre "CONSILIUM MEDICAL"	Kyiv
Ukraine	Municipal Non-Profit Enterprise "Consultative and Diagnostic centre" of Pechersk District of Kiyv	Kyiv
Ukraine	National Scientific Center Institute of Cardiology of M.D	Kyiv
Ukraine	State Institution "National Scientific Center "Institute of Cardiology	Kyiv
Ukraine	"Oleksandrivska Clinical Hospital of Kyiv" of executive authority Kyiv City	Kyiv,
Ukraine	Communal Noncommercial Enterprise of Lviv Regional Council "Lviv Regional Clinical	Lviv
Ukraine	MNPE "Lviv City Clinical Hospital No.5"	Lviv
Ukraine	"Vinnytsia Regional Clinical Treatment Diagnostic Center of Cardiovascular Pathology"	Vinnytsia
Ukraine	Vinnytsia Regional Clinical Hospital of Veterans of War	Vinnytsia
Ukraine	?ommunal Institution "Zaporizhzhia Regional Clinical Hospital" of Zaporizhzhia Regional Council,	Zaporizhzhia
Ukraine	Communal Non-Profit Enterprise "City	Zaporizhzhia
Ukraine	Educational and Research Medical Center "University Clinic" at Zaporizhzhia State Medical University of the Ministry of Health of Ukraine,	Zaporizhzhia
Ukraine	Communal Enterprise "Hospital ?1" of Zhytomyr City Council	Zhytomyr
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Advanced Cardiovascular LLC	Alexander City	Alabama
United States	Alexandria Cardiology Clinic	Alexandria	Louisiana
United States	Amarillo Hearth Clinical Research Institute, Inc.	Amarillo	Texas
United States	PharmaTex Research	Amarillo	Texas
United States	Alaska Heart & Vascular Institute	Anchorage	Alaska
United States	Anne Arundel Health System Research Institute	Annapolis	Maryland
United States	Asheville Cardiology Associates	Asheville	North Carolina
United States	Piedmont Heart Institute - Athens	Athens	Georgia
United States	Piedmont Heart Institute	Atlanta	Georgia
United States	Advanced Cardiovascular, LLC	Auburn	Alabama
United States	Augusta University	Augusta	Georgia
United States	University Cardiology Associates, LLC	Augusta	Georgia
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Suburban Hospital	Bethesda	Maryland
United States	Westside Medical Associates of Los Angeles	Beverly Hills	California
United States	Saint Luke's Boise Medical Center	Boise	Idaho
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Cardiology Associates of South Florida	Boynton Beach	Florida
United States	Cardiovascular & Vein Center of Florida	Bradenton	Florida
United States	New York Presbyterian Brooklyn Methodist Hospital	Brooklyn	New York
United States	The University of Vermont Medical Center	Burlington	Vermont
United States	Penn State Health Holy Spirit Medical Center Geisinger - Cardiology	Camp Hill	Pennsylvania
United States	Aultman Cardiology Clinical Trials	Canton	Ohio
United States	Harbor-UCLA Medical Center	Carson	California
United States	Trinity Medical WNY, PC	Cheektowaga	New York
United States	Mount Sinai Hospital Medical Center - Department of Cardiology	Chicago	Illinois
United States	Innovative Research of West Florida, Inc.	Clearwater	Florida
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	The MetroHealth System	Cleveland	Ohio
United States	Prisma Health	Columbia	South Carolina
United States	The Ohio State University	Columbus	Ohio
United States	Verde Valley Medical Center	Cottonwood	Arizona
United States	Valley Clinical Trials, Inc.	Covina	California
United States	Baylor University Medical Center	Dallas	Texas
United States	Cardiovascular Research Institute of Dallas	Dallas	Texas
United States	Dallas VA Medical Center	Dallas	Texas
United States	Southwest Family Medicine Associates	Dallas	Texas
United States	Danbury Hospital	Danbury	Connecticut
United States	Avail Clinical Research, LLC	DeLand	Florida
United States	Duke University Heart Failure Research	Durham	North Carolina
United States	Monmouth Cardiology Associates, LLC	Eatontown	New Jersey
United States	Riverside Clinical Research	Edgewater	Florida
United States	TriWest Research Associates, LLC	El Cajon	California
United States	North Ohio Heart Center	Elyria	Ohio
United States	Englewood Health	Englewood	New Jersey
United States	Providence Regional Medical Center Everett	Everett	Washington
United States	Medicoricium, LLC	Fairview Heights	Illinois
United States	NECCR Prima Care Research, LLC	Fall River	Massachusetts
United States	Piedmont Heart Institute Fayetteville	Fayetteville	Georgia
United States	Advanced Heart & Vascular Institute of Hunterdon	Flemington	New Jersey
United States	Sparks Regional Medical Center	Fort Smith	Arkansas
United States	Parkview Research Center	Fort Wayne	Indiana
United States	Texas Health Research & Education Institute	Fort Worth	Texas
United States	Stern Cardiovascular Foundation	Germantown	Tennessee
United States	Genesys Regional Medical Center	Grand Blanc	Michigan
United States	Medication Management, LLC	Greensboro	North Carolina
United States	Self Regional Hospital Research Center	Greenwood	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Heart Clinic of Hammond	Hammond	Louisiana
United States	Wake Forest University Health Sciences	High Point	North Carolina
United States	Memorial Regional Hospital	Hollywood	Florida
United States	Cardiovascular Institute of the South	Houma	Louisiana
United States	Texas Heart Institute	Houston	Texas
United States	California Heart Specialists	Huntington Beach	California
United States	Franciscan Physician Network - Indiana Heart Physicians	Indianapolis	Indiana
United States	St. Vincent Medical Group	Indianapolis	Indiana
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	St. Vincent's Healthcare - Riverside	Jacksonville	Florida
United States	St. Vincent's Healthcare - Southside Recruiting	Jacksonville	Florida
United States	UF Health Jacksonville	Jacksonville	Florida
United States	NEA Baptist Clinic	Jonesboro	Arkansas
United States	Western Michigan University Homer Stryker M.D. School of Medicine	Kalamazoo	Michigan
United States	Houston Heart & Vascular Associates	Kingwood	Texas
United States	Tennova Healthcare-Turkey Creek Medical Center	Knoxville	Tennessee
United States	Carolina Heart Specialists	Lancaster	South Carolina
United States	First Valley Medical Group	Lancaster	California
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	Red Rock Clinical Research, LLC	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Nebraska Heart Institute	Lincoln	Nebraska
United States	Arkansas Heart Hospital	Little Rock	Arkansas
United States	South Denver Cardiology Associates, PC	Littleton	Colorado
United States	Healthcare Partners Affiliation Medical Group	Long Beach	California
United States	Axis Clinical Trials	Los Angeles	California
United States	Caprock Cardiac Center Research Institute, Inc.	Lubbock	Texas
United States	Angelina Medical Research, LLC	Lufkin	Texas
United States	Duke Cardiology of Lumberton	Lumberton	North Carolina
United States	Stroobants Cardiovascular Center	Lynchburg	Virginia
United States	Georgia Arrhythmia Consultants and Research Institute	Macon	Georgia
United States	Mercer University	Macon	Georgia
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	North Dallas Research Associates	McKinney	Texas
United States	North Texas Research Associates	McKinney	Texas
United States	Cordova Research Institute, LLC	Miami	Florida
United States	ITB Research	Miami	Florida
United States	Med-Care Research	Miami	Florida
United States	ProLive Medical Research	Miami	Florida
United States	Vista Health Research	Miami	Florida
United States	Empire Clinical Research, LLC	Miami Lakes	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Allina Health System, dba Abbott Northwestern Hospital	Minneapolis	Minnesota
United States	Trinity Health Center - Medical Arts	Minot	North Dakota
United States	St. Joseph Heritage-Healthcare	Mission Viejo	California
United States	IMC/Diagnostic & Medical Clinic	Mobile	Alabama
United States	University of South Alabama	Mobile	Alabama
United States	Monroe Biomedical Research	Monroe	North Carolina
United States	Crossroads Clinical Research, Inc.	Mooresville	North Carolina
United States	Indiana University Health Ball Memorial Hospital, Inc.	Muncie	Indiana
United States	Saint Peter's University Hospital	New Brunswick	New Jersey
United States	Ochsner Health System	New Orleans	Louisiana
United States	Tulane Heart & Vascular Institute	New Orleans	Louisiana
United States	Mount Sinai Hospital	New York	New York
United States	Christiana Care	Newark	Delaware
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Saint Michael's Medical Center	Newark	New Jersey
United States	Radin Cardiovascular Medical Group, Inc.	Newport Beach	California
United States	Riverside Cardiology Specialists	Newport News	Virginia
United States	Sentara Norfolk General Hospital	Norfolk	Virginia
United States	North Kansas City Hospital	North Kansas City	Missouri
United States	Valley Clinical Trials, Inc.	Northridge	California
United States	Parkway Cardiology Associates, PC	Oak Ridge	Tennessee
United States	South Oklahoma Heart Research, LLC	Oklahoma City	Oklahoma
United States	CHI Health Research Center	Omaha	Nebraska
United States	Florida Hospital Transplant Institute	Orlando	Florida
United States	Cardiology Partners Clinical Research Institute	Palm Beach Gardens	Florida
United States	Springfield Medical Center	Panama City	Florida
United States	Pasadena Clinical Research	Pasadena	California
United States	Broward Research Center	Pembroke Pines	Florida
United States	South Florida Research Solutions, LLC	Pembroke Pines	Florida
United States	Avanza Medical Research Center	Pensacola	Florida
United States	Cardiology Consultants	Pensacola	Florida
United States	Drexel University	Philadelphia	Pennsylvania
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pennsylvania - Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	Pinehurst Medical Clinic, Inc.	Pinehurst	North Carolina
United States	V.A. Pittsburgh Healthcare System	Pittsburgh	Pennsylvania
United States	AtlantiCare Regional Medical Center	Pomona	New Jersey
United States	Eugene Soroka, MD Inc.	Port Hueneme	California
United States	NC Heart & Vascular Research	Raleigh	North Carolina
United States	WakeMed Health and Hospitals	Raleigh	North Carolina
United States	Black Hills Cardiovascular Research, a department of Rapid City Regional Hospital, Inc.	Rapid City	South Dakota
United States	Hunter Holmes McGuire V.A. Medical Center - Cardiology Div. (111J)	Richmond	Virginia
United States	Reid Physician Associates / Reid Health	Richmond	Indiana
United States	VCU Medical Center	Richmond	Virginia
United States	The Valley Hospital	Ridgewood	New Jersey
United States	Carilion Medical Center	Roanoke	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Rochester General Hospital	Rochester	New York
United States	Michigan CardioVascular Institute at Covenant Medical Center	Saginaw	Michigan
United States	St. Louis Heart & Vascular, PC	Saint Louis	Missouri
United States	Professional Health Care of Pinellas	Saint Petersburg	Florida
United States	South Texas Cardiovascular Consultants, PLLC	San Antonio	Texas
United States	VA San Diego Health Care System	San Diego	California
United States	North Ohio Heart Center	Sandusky	Ohio
United States	Maine Medical Partners Maine Health Cardiology	Scarborough	Maine
United States	Swedish Heart & Vascular-Advanced Cardiac Support Program	Seattle	Washington
United States	Louisiana Heart Center	Slidell	Louisiana
United States	Atlanta Vanguard Research Institute	Smyrna	Georgia
United States	Cardio Metabolic Institute	Somerset	New Jersey
United States	Beacon Medical Group Advanced Cardiovascular Specialists	South Bend	Indiana
United States	Providence Sacred Heart Medical Center & Children's Hospital	Spokane	Washington
United States	Heart House Research Foundation	Springfield	Ohio
United States	Stamford Hospital	Stamford	Connecticut
United States	Richmond University Medical Center	Staten Island	New York
United States	Stony Brook University Hospital	Stony Brook	New York
United States	Clinical Research Institute of Arizona, LLC	Surprise	Arizona
United States	CHI Franciscan Research Center	Tacoma	Washington
United States	Holy Name Medical Center	Teaneck	New Jersey
United States	Baylor Scott & White Medical Center	Temple	Texas
United States	Carondelet Heart and Vascular Institute - Cardiology East	Tucson	Arizona
United States	Cardiology Associates Research, LLC	Tupelo	Mississippi
United States	PharmaTex Research	Tyler	Texas
United States	The University of Texas Health Center at Tyler	Tyler	Texas
United States	Indian River Medical Center	Vero Beach	Florida
United States	Walla Walla Clinic	Walla Walla	Washington
United States	ProHealth Care Inc / Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	Cardiology Partners Clinical Research Institute	Wellington	Florida
United States	Wenatchee Valley Hospital & Clinics	Wenatchee	Washington
United States	Interventional Cardiology Medical Group	West Hills	California
United States	Advanced Clinical Research/Intermountain Heart Center PC	West Jordan	Utah
United States	Circuit Clinical	West Seneca	New York
United States	Wichita Falls Heart Clinic	Wichita Falls	Texas
United States	Northtowns Cardiology, PLLC	Williamsville	New York
United States	Alfieri Cardiology	Wilmington	Delaware
United States	PMG Research of Wilmington	Wilmington	North Carolina
United States	Selma Medical Associates	Winchester	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
American Regent, Inc.	Duke Clinical Research Institute

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Czechia,  Georgia,  Hungary,  Latvia,  Lithuania,  New Zealand,  Poland,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of death		1 year
Primary	Incidence of hospitalization for heart failure		1 year
Primary	Change in 6MWT distance		6 months