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International Study to Determine if AdreView Heart Function Scan Can be Used to Identify Patients With Mild or Moderate Heart Failure (HF) That Benefit From Implanted Medical Device

Phase 3
Terminated
Conditions
Heart Failure
Interventions
Device: Implantable Cardioverter Defibrillator
Drug: Thyroid blocking
Registration Number
NCT02656329
Lead Sponsor
GE Healthcare
Brief Summary

This is an event-driven Phase IIIb, multicentre, randomised, clinical study to demonstrate the efficacy of AdreView™ imaging for appropriately guiding the decision of implantable cardioverter defibrillator (ICD) implantation, in New York Health Association (NYHA) class II and III heart failure participants with 25%\<=left ventricular ejection fraction (LVEF)\<=35%, and in particular, for identifying participants who are at low risk for sudden cardiac death and who would not benefit, or may suffer harm, from implantation of an ICD device.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
395
Inclusion Criteria
  • Participants >=18 years of age at the time dated informed consent was obtained.
  • Female participants must be pre-menarchal, surgically sterile (had a documented bilateral oophorectomy and/or documented hysterectomy), postmenopausal (cessation of menses for more than 1 year), non-lactating, or, if of childbearing potential, a serum or urine pregnancy test with the results known prior to AdreView (Iobenguane I-123 Injection) administration) was negative.
  • Participants willing and able to comply with all study procedures and a signed and dated informed consent was obtained before any study-procedure was carried out.
  • Heart failure NYHA class II or III for symptoms, participants with ischemic or non-ischemic heart disease, eligible for ICD implantation as per each site's standard of practice.
  • Non-ischemic dilated cardiomyopathy or ischemic heart disease of at least 3 months duration receiving guideline-directed optimal medical therapy.
  • 25%≤LVEF≤35%, performed within 3 months before or at time of enrollment, as measured by radionuclide ventriculography, or electrocardiogram [ECG]-gated SPECT myocardial perfusion imaging [MPI], or magnetic resonance imaging [MR], computed tomography [CT], or 3D or 2D echocardiography [Simpson's or multidisc method only, M-mode echocardiography was not accepted].

In case LVEF measurement was performed within 3 months before enrollment, measurement should be performed at least 40 days after a hospitalization for HF or acute coronary syndrome (including myocardial infarction), and to be valid, method of measurement should be in accordance with the protocol and the imaging exam should be made available to the Sponsor in digital format. In case several valid LVEF measurements are available, the closest to enrollment will be used for inclusion determination.

  • Clinically stable heart failure in the medical judgment of the investigator (i.e. no significant changes in medication, no worsening of symptoms, no unscheduled visits to the doctor's office) for the past 30 days and no hospitalization for heart failure or acute coronary syndrome (including myocardial infarction) in the past 40 days.
  • Reasonable expectation of meaningful survival for at least 1 year.
Exclusion Criteria
  • Participants with existing ICD or participant having an indication of ICD implantation for secondary prevention of sudden cardiac death.
  • Hospitalization for HF or for acute coronary syndrome in the previous 40 days.
  • Participants where a cardiac resynchronisation therapy (CRT) was planned or indicated.
  • Other indication for placement of device (sustained ventricular tachycardia, resuscitated sudden death, need for atrioventricular pacing).
  • NYHA class I or class IV symptoms at the time of study entry.
  • Participants with chronic renal insufficiency defined as serum creatinine ≥ 3 mg/dl (or ≥ 265.2 µmol/L).
  • American College of College-American Heart Association (ACC-AHA) class III or class IV (unstable) angina.
  • Known or suspected hypersensitivity/allergy to Iobenguane or to any of the excipients an Adreview (Iobenguane I-131 injection).
  • Participant who was pregnant or plans to become pregnant within 2 weeks after AdreView (Iobenguane I-123 Injection) administration.
  • Participant who had used any medication in the 2 weeks before AdreView (Iobenguane I-123 Injection) that could interfere with the test: e.g. but not limited to amitriptyline or derivatives, imipramine or derivatives, other antidepressants or drugs known or suspected to inhibit the norepinephrine transporter, antihypertensives that deplete norepinephrine stores or inhibit reuptake, sympathomimetic amines or cocaine.
  • Participants that had a medical condition that could interfere with the AdreView test (e.g. but not limited to left ventricular assist device (LVAD), or prior heart transplant).
  • Participants who participated in a clinical study involving a drug or device within 30 days prior to study entry and participants participating in any other clinical study.
  • Participants having serious non-cardiac medical condition associated with significant elevation of plasma catecholamines, including pheochromocytoma.
  • Participants with a clinical diagnosis of (or being treated for) Parkinson's disease or Multiple System Atrophy.
  • The participant had participated in a research study using ionizing radiation in the previous 12 months.
  • Participants previously randomized in this study.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
AdreView™Iobenguane I -123 InjectionParticipants received 1 intravenous injection of 10 mCi (370 MBq) of AdreView™ (Iobenguane I-123 Injection). Participants with AdreView™ Heart-to-Mediastinal ratio (H/M) \<1.6 underwent Implantable Cardioverter Defibrillator (ICD) device implantation and H/M \>= 1.6 continued to receive Guideline-Directed Optimal Medical Therapy (GDMT) according to clinical standard practice.
Standard of CareIobenguane I -123 InjectionParticipants received 1 intravenous injection of 10 mCi (370 MBq) of AdreView™ (Iobenguane I-123 Injection) and underwent ICD implantation and were followed up in accordance with internationally accepted Heart Failure (HF) guidelines.
AdreView™Implantable Cardioverter DefibrillatorParticipants received 1 intravenous injection of 10 mCi (370 MBq) of AdreView™ (Iobenguane I-123 Injection). Participants with AdreView™ Heart-to-Mediastinal ratio (H/M) \<1.6 underwent Implantable Cardioverter Defibrillator (ICD) device implantation and H/M \>= 1.6 continued to receive Guideline-Directed Optimal Medical Therapy (GDMT) according to clinical standard practice.
Standard of CareImplantable Cardioverter DefibrillatorParticipants received 1 intravenous injection of 10 mCi (370 MBq) of AdreView™ (Iobenguane I-123 Injection) and underwent ICD implantation and were followed up in accordance with internationally accepted Heart Failure (HF) guidelines.
AdreView™Thyroid blockingParticipants received 1 intravenous injection of 10 mCi (370 MBq) of AdreView™ (Iobenguane I-123 Injection). Participants with AdreView™ Heart-to-Mediastinal ratio (H/M) \<1.6 underwent Implantable Cardioverter Defibrillator (ICD) device implantation and H/M \>= 1.6 continued to receive Guideline-Directed Optimal Medical Therapy (GDMT) according to clinical standard practice.
Primary Outcome Measures
NameTimeMethod
All-cause MortalityFrom randomization until the end of the follow-up period (median 304 days)

All-cause mortality included all reported deaths of participants during the study due to any cause. Percentage of participants who died due to any cause were reported.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Cardiac DeathFrom randomization until the end of the follow-up period (median 304 days)

Cardiac death composed of sudden cardiac death, death due to cardiac arrhythmia, death due to heart failure, and death due to other cardiovascular causes.

Percentage of Participants With Hospitalization for Cardiovascular CauseFrom randomization until the end of the follow-up period (median 304 days)

Percentage of participants who were hospitalized for cardiovascular cause were reported.

Percentage of Participants With All-Cause HospitalizationFrom randomization until the end of the follow-up period (median 304 days)

Percentage of participants with all-cause hospitalization were reported.

Percentage of Participants With Events (Composite of the Occurrence of Resuscitated Life-Threatening Ventricular Tachycardia, Unstable Ventricular Tachyarrhythmias, Sudden Cardiac Death [SCD] and Resuscitated Cardiac Arrest)From randomization until the end of the follow-up period (median 304 days)

Percentage of participants with composite events i.e occurrence of resuscitated life-threatening ventricular tachycardia, unstable ventricular tachy-arrhythmias, SCD and resuscitated cardiac arrest were reported. Participants who were alive at time of database lock (DBL) were censored at the last known-alive date.

Percentage of Participants With Events of Complications of Device: H/M >=1.6 in Full Analysis SetFrom randomization until the end of the follow-up period (median 304 days)

Composite of the percentage of participants with events of hospitalization or death related to major complications of device implantation (i.e., need for thoracotomy, pericardiocentesis, or vascular surgery), complications of long-term device therapy (i.e., infection not leading to hospitalization, lead and/or generator removal/replacement, inappropriate shocks, explanation), and combined as 'complications of device' for participants with H/M \>=1.6. Participants who were alive at time of database lock (DBL) were censored at the last known-alive date.

Percentage of Participants With SyncopeFrom randomization until the end of the follow-up period (median 304 days)

Percentage of participants with Syncope were reported. Participants who were alive at time of DBL were censored at the last known-alive date by date of DBL.

Percentage of Participants With Implantable Cardioverter Defibrillator (ICD) ImplantationFrom randomization until the end of the follow-up period (median 304 days)

Percentage of participants with ICD implantation were reported.

Percentage of Participants With Events of Complications of DeviceFrom randomization until the end of the follow-up period (median 304 days)

Composite of the percentage of participants with events of hospitalization or death related to major complications of device implantation (i.e., need for thoracotomy, pericardiocentesis, or vascular surgery), complications of long-term device therapy (i.e., infection not leading to hospitalization, lead and/or generator removal/replacement, inappropriate shocks, explanation), and combined as 'complications of device'.

Trial Locations

Locations (94)

CIUSSS de L'Estrie - CHUS Hopital Fleurimont

🇨🇦

Sherbrooke, Quebec, Canada

Comprehensive Cardiovascular Medical Group

🇺🇸

Bakersfield, California, United States

Sharp Grossmont Hospital

🇺🇸

La Mesa, California, United States

Cardiology Physicians PA/Red Clay Research, LLC

🇺🇸

Newark, Delaware, United States

Augusta University

🇺🇸

Augusta, Georgia, United States

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

Northwestern University

🇺🇸

Evanston, Illinois, United States

Boston Medical Center

🇺🇸

Boston, Massachusetts, United States

University at Buffalo

🇺🇸

Buffalo, New York, United States

Advanced Cardiology Group

🇺🇸

Buffalo, New York, United States

Veterans Affairs North Texas Healthcare System

🇺🇸

Dallas, Texas, United States

WakeMed

🇺🇸

Raleigh, North Carolina, United States

Texas Institute of Cardiology, PA

🇺🇸

McKinney, Texas, United States

Houston Methodist Hospital

🇺🇸

Houston, Texas, United States

Victoria Heart and Vascular Center

🇺🇸

Victoria, Texas, United States

London Health Sciences Centre

🇨🇦

London, Ontario, Canada

Institut Universitaire De Cardiologie Et De Pneumologie De Quebec

🇨🇦

Quebec, Canada

Fakultni nemocnice u sv. Anny v Brne

🇨🇿

Brno, Czechia

Fakultni nemocnice Brno Bohunice

🇨🇿

Brno, Czechia

FN Hradec Kralove

🇨🇿

Hradec Kralove, Czechia

Krajska nemocnice Liberec

🇨🇿

Liberec, Czechia

Fakultni nemocnice v Motole

🇨🇿

Praha 5, Czechia

Fakultni nemocnice Plzen

🇨🇿

Lochotín, Czechia

Fakultni nemocnice v Kralovske Vinohrady

🇨🇿

Praha 10, Czechia

Masarykova nemocnice v Usti nad Labem

🇨🇿

Usti nad Labem, Czechia

CH Antoine Beclere

🇫🇷

Clamart, France

CHU Henri Mondor

🇫🇷

Créteil, France

CHRU de Lille

🇫🇷

Lille, France

Clinique Pasteur

🇫🇷

Toulouse, France

Hopitaux de Brabois Chu Nancy

🇫🇷

Vandoeuvre Les Nancy Cedex, France

Klinik & Poliklinik fur Nuklearmedizin, LMU, Campus Grobhader

🇩🇪

Munich, Germany

Debreceni Egyetem, Kardiologia Intezet and ScanoMed Nuclear Medicine Institute

🇭🇺

Debrecen, Hungary

Semmelweis Egyetem Nuklearis Medicina Kozpont

🇭🇺

Budapest, Hungary

Ospedale Santa Maria di Ca' Foncello

🇮🇹

Treviso, Italy

Ospedale dell'Angelo, 30174, Venezia Mestre

🇮🇹

Venice, Italy

Onze Lieve Vrouwen Gasthuis

🇳🇱

Amsterdam, Netherlands

Academic Medical Center

🇳🇱

Amsterdam, Netherlands

Amphia Zickenhuis

🇳🇱

Breda, Netherlands

Uniwersyteckie Centrum Kliniczne

🇵🇱

Gdańsk, Poland

Krakowski Szpital Specjalistyczny im. Jana Pawla II

🇵🇱

Krakow, Poland

Wojskowy Instytut Medyczny

🇵🇱

Warsaw, Poland

Samodzielny Publiczny Centralny Szpital Kliniczny

🇵🇱

Warsaw, Poland

Dolnośląski Szpital Specjalistyczny im. T. Marciniaka Centrum Medycyny Ratunkowej

🇵🇱

Wrocław, Poland

Hospital Universitario Virgen de las Nieves

🇪🇸

Granada, Spain

Hospital Clinico Universitario Virgen de la Arrixaca

🇪🇸

El Palmar (Murcia), Spain

Hospital Universitario de Leon

🇪🇸

León, Spain

Hospital Universitario Ramon y Cajal

🇪🇸

Madrid, Spain

Hospital Clinico Universitario San Carlos

🇪🇸

Madrid, Spain

Hospital Universitario Virgen de la Victoria

🇪🇸

Malaga, Spain

Hospital Clínico de Salamanca

🇪🇸

Salamanca, Spain

Hospital Universitario Son Espases

🇪🇸

Palma de Mallorca (Illes Balears), Spain

Hospital Universitario San Juan de Alicante

🇪🇸

San Juan Alicante, Spain

Complejo Hospitalario Universitario de Santiago

🇪🇸

Santiago De Compostela (A Coruña), Spain

Hospital General Universitario de Valencia

🇪🇸

Valencia, Spain

Regions Hospital and Regions Heart Center Clinic

🇺🇸

Saint Paul, Minnesota, United States

Coromed-SMO ft.

🇭🇺

Pécs, Hungary

Ospedale Santa Croce

🇮🇹

Moncalieri, Italy

Instituti Clinici Scientifici Maugeri Spa Societa Benefit

🇮🇹

Pavia, Italy

University of Calgary

🇨🇦

Calgary, Alberta, Canada

Venezia Mestre - Azienda ULSS 12 "Veneziana"

🇮🇹

Venezia, Italy

Leiden University Medical Center

🇳🇱

Leiden, Netherlands

University of Florida Health Jacksonville

🇺🇸

Jacksonville, Florida, United States

Royal Alexandra Hospital

🇨🇦

Edmonton, Alberta, Canada

South Miami Heart Specialists

🇺🇸

South Miami, Florida, United States

Varosmajori Sziv es Ergyogyaszati Klinika

🇭🇺

Budapest, Hungary

Gottsegen Gyorgy Orszagos Kardiologiai Intezet

🇭🇺

Budapest, Hungary

MMP ME Health Cardiology

🇺🇸

Scarborough, Maine, United States

CHR Metz-Thionville - Site de Mercy

🇫🇷

Ars Laquenexy, France

Hopital de Rangueil CHU Toulouse

🇫🇷

Toulouse Cedex 9, France

Area Cardiologia Critica - IRCCS Centro Cardiologico Mozino

🇮🇹

Milano, Italy

Azienda Ospedaliero-Universitaria Federico II Dipartimento ad Attivita Integrata di Cardiologia,Cardiochirurgia ed Emergenze Cardiovascolari

🇮🇹

Napoli, Italy

Azienda Ospedaliero-Universitaria Maggiore della Carità, Dipartimento Cardiologico, Cardiologia 1

🇮🇹

Novara, Italy

Dipartimento di Scienze Cardiovascolari, Respiratorie Neufrologiche e Geriatriche - Universita di Roma "La Sapienza"

🇮🇹

Rome, Italy

VA Connecticut Healthcare System (VACHS)

🇺🇸

West Haven, Connecticut, United States

Magyar Honvedseg Egeszsegugyi Kozpont Kardiológia Osztály/Nuklearis Medicina Osztaly

🇭🇺

Budapest, Hungary

St. Michael's Hospital

🇨🇦

Toronto, Ontario, Canada

Montreal Heart Institute

🇨🇦

Montreal, Quebec, Canada

CHU Clermont-Ferrand, 63003 Montalembert

🇫🇷

Clermont-Ferrand, France

Kliniken Maria Hilf GmbH, Klinik fur Nuklearmedizin

🇩🇪

Monchengladbach, Germany

Cardiology Consultants

🇺🇸

Pensacola, Florida, United States

Uniwersytecki Szpital Kliniczny w Bialymstoku

🇵🇱

Bialystok, Poland

Azienda Ospedaliera Universitaria G. Martino

🇮🇹

Messina, Italy

Maastricht University Medical Center

🇳🇱

Maastricht, Netherlands

Samodzielny Publiczny Szpital Kliniczny Nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach

🇵🇱

Katowice, Poland

Bethesda Health

🇺🇸

Boynton Beach, Florida, United States

MedStar Shah Medical Group

🇺🇸

Charlotte Hall, Maryland, United States

Budai Irgalmasrendi Korhaz

🇭🇺

Budapest, Hungary

University of South Florida

🇺🇸

Tampa, Florida, United States

Department of Cardiology, K-14 (Henry Ford Health System)

🇺🇸

Detroit, Michigan, United States

Yale New Haven Hospital

🇺🇸

New Haven, Connecticut, United States

Tampa General Hospital

🇺🇸

Tampa, Florida, United States

Vascular Biology and Hypertension Program, University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

University of Miami Hospital

🇺🇸

Miami, Florida, United States

Montefiore Medical Center

🇺🇸

Bronx, New York, United States

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