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 (ADMIRE-ICD)

AdreView™ Myocardial Imaging for Risk Evaluation - A Multicentre Trial to Guide ICD Implantation in NYHA Class II & III Heart Failure Patients With 25%≤LVEF≤35%

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.

Study Overview

• Status: Terminated
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Iobenguane I -123 Injection; Device: Implantable Cardioverter Defibrillator; Drug: Thyroid blocking; Device: Implantable Cardioverter Defibrillator

• Study Type: Interventional
• Enrollment (Actual): 395
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • Institut universitaire de Cardiologie et de Pneumologie de Quebec
  • Alberta
    • Calgary, Alberta, Canada, T2N 1N4
      • University of Calgary
    • Edmonton, Alberta, Canada, T5H3V9
      • Royal Alexandra Hospital
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • CIUSSS de L'Estrie - CHUS Hopital Fleurimont
• Czechia
  • Brno, Czechia, 656 91
    • Fakultni nemocnice u sv. Anny v Brne
  • Brno, Czechia, 625 00
    • Fakultní nemocnice Brno Bohunice
  • Hradec Kralove, Czechia, 500 05
    • FN Hradec Kralove
  • Liberec, Czechia, 460 63
    • Krajska Nemocnice Liberec
  • Lochotín, Czechia, 304 60
    • Fakultní nemocnice Plzeň
  • Praha 10, Czechia, 100 34
    • Fakultni nemocnice v Kralovske Vinohrady
  • Praha 5, Czechia, 150 06
    • Fakultní nemocnice v Motole
  • Usti nad Labem, Czechia, 40001
    • Masarykova Nemocnice V Usti Nad Labem
• France
  • Ars Laquenexy, France, 57530
    • CHR Metz-Thionville - Site de Mercy
  • Clamart, France, 92140
    • Ch Antoine Beclere
  • Clermont-Ferrand, France
    • CHU Clermont-Ferrand, 63003 Montalembert
  • Créteil, France, 94010
    • CHU Henri Mondor
  • Lille, France, 59037
    • CHRU de Lille
  • Toulouse, France, 31300
    • Clinique Pasteur
  • Toulouse Cedex 9, France, 31059
    • Hopital de Rangueil CHU Toulouse
  • Vandoeuvre Les Nancy Cedex, France, 54511
    • Hopitaux de Brabois Chu Nancy
• Germany
  • Monchengladbach, Germany, 41063
    • Kliniken Maria Hilf GmbH, Klinik fur Nuklearmedizin
  • Munich, Germany
    • Klinik & Poliklinik fur Nuklearmedizin, LMU, Campus Grobhader
• Hungary
  • Budapest, Hungary, 1112
    • Varosmajori Sziv es Ergyogyaszati Klinika
  • Budapest, Hungary, H-1023
    • Budai Irgalmasrendi Korhaz
  • Budapest, Hungary, H-1134
    • Gottsegen György Országos Kardiológiai Intézet
  • Budapest, Hungary, H-1134
    • Magyar Honvedseg Egeszsegugyi Kozpont Kardiológia Osztály/Nuklearis Medicina Osztaly
  • Budapest, Hungary
    • Semmelweis Egyetem Nuklearis Medicina Kozpont
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem, Kardiologia Intezet and ScanoMed Nuclear Medicine Institute
  • Pécs, Hungary, H-7623
    • Coromed-SMO ft.
• Italy
  • Messina, Italy, 98125
    • Azienda Ospedaliera Universitaria G. Martino
  • Milano, Italy, 20138
    • Area Cardiologia Critica - IRCCS Centro Cardiologico Mozino
  • Moncalieri, Italy, 10024
    • Ospedale Santa Croce
  • Napoli, Italy, 80131
    • Azienda Ospedaliero-Universitaria Federico II Dipartimento ad Attivita Integrata di Cardiologia,Cardiochirurgia ed Emergenze Cardiovascolari
  • Novara, Italy, 28100
    • Azienda Ospedaliero-Universitaria Maggiore della Carità, Dipartimento Cardiologico, Cardiologia 1
  • Pavia, Italy, 27100
    • Instituti Clinici Scientifici Maugeri Spa Societa Benefit
  • Rome, Italy, 00161
    • Dipartimento di Scienze Cardiovascolari, Respiratorie Neufrologiche e Geriatriche - Universita di Roma "La Sapienza"
  • Treviso, Italy, 31100
    • Ospedale Santa Maria di Ca' Foncello
  • Venezia, Italy, 30174
    • Venezia Mestre - Azienda ULSS 12 "Veneziana"
  • Venice, Italy
    • Ospedale dell'Angelo, 30174, Venezia Mestre
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academic Medical Center
  • Amsterdam, Netherlands, 1091 AC
    • Onze Lieve Vrouwen Gasthuis
  • Breda, Netherlands, 4818 CK
    • Amphia Zickenhuis
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center
  • Maastricht, Netherlands, 6229 HX
    • Maastricht University Medical Center
• Poland
  • Bialystok, Poland, 15-276
    • Uniwersytecki Szpital Kliniczny w Bialymstoku
  • Gdańsk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne
  • Katowice, Poland, 40-635
    • Samodzielny Publiczny Szpital Kliniczny nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach
  • Krakow, Poland, 31-202
    • Krakowski Szpital Specjalistyczny Im. Jana Pawla Ii
  • Warsaw, Poland, 04-141
    • Wojskowy Instytut Medyczny
  • Warsaw, Poland
    • Samodzielny Publiczny Centralny Szpital Kliniczny
  • Wrocław, Poland, 54-049
    • Dolnośląski Szpital Specjalistyczny im. T. Marciniaka Centrum Medycyny Ratunkowej
• Spain
  • El Palmar (Murcia), Spain, 30120
    • Hospital Clínico Universitario Virgen de la Arrixaca
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de las Nieves
  • León, Spain, 24071
    • Hospital Universitario de Leon
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28040
    • Hospital Clínico Universitario San Carlos
  • Malaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Palma de Mallorca (Illes Balears), Spain, 07120
    • Hospital Universitario Son Espases
  • Salamanca, Spain, 37002
    • Hospital Clinico De Salamanca
  • San Juan Alicante, Spain, 03550
    • Hospital Universitario San Juan de Alicante
  • Santiago De Compostela (A Coruña), Spain, 15706
    • Complejo Hospitalario Universitario de Santiago
  • Valencia, Spain, 46014
    • Hospital General Universitario De Valencia
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Vascular Biology and Hypertension Program, University of Alabama at Birmingham
  • California
    • Bakersfield, California, United States, 93309
      • Comprehensive Cardiovascular Medical Group
    • La Mesa, California, United States, 91942
      • Sharp Grossmont Hospital
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale New Haven Hospital
    • West Haven, Connecticut, United States, 06516
      • VA Connecticut Healthcare System (VACHS)
  • Delaware
    • Newark, Delaware, United States, 19713
      • Cardiology Physicians PA/Red Clay Research, LLC
  • Florida
    • Boynton Beach, Florida, United States, 33435
      • Bethesda Health
    • Jacksonville, Florida, United States, 32209
      • University of Florida Health Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami Hospital
    • Pensacola, Florida, United States, 32501
      • Cardiology Consultants
    • South Miami, Florida, United States, 33143
      • South Miami Heart Specialists
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
    • Tampa, Florida, United States, 33609
      • University of South Florida
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Evanston, Illinois, United States, 60208
      • Northwestern University
  • Maine
    • Scarborough, Maine, United States, 04074
      • MMP ME Health Cardiology
  • Maryland
    • Charlotte Hall, Maryland, United States, 20622
      • MedStar Shah Medical Group
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Department of Cardiology, K-14 (Henry Ford Health System)
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital and Regions Heart Center Clinic
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Buffalo, New York, United States, 14203
      • University at Buffalo
    • Buffalo, New York, United States, 14215
      • Advanced Cardiology Group
  • North Carolina
    • Raleigh, North Carolina, United States, 27610
      • WakeMed
  • Texas
    • Dallas, Texas, United States, 75216
      • Veterans Affairs North Texas Healthcare System
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • McKinney, Texas, United States, 75071
      • Texas Institute of Cardiology, PA
    • Victoria, Texas, United States, 77901
      • Victoria Heart and Vascular Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: AdreView™; Participants 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.	Drug: Iobenguane I -123 Injection; Iobenguane I-123 Injection, AdreView. All participants scheduled for an Iobenguane I-123 Injection, AdreView scan.; Other Names: AdreView; Iobenguane I-123 Injection; Device: Implantable Cardioverter Defibrillator; In the Iobenguane I-123 Injection group, participants with H/M ratio less or equal to 1.6 underwent ICD device implantation, while those with H/M ratio greater than or equal to 1.6 did not undergo ICD implantation.; Drug: Thyroid blocking; Participants received a thyroid blocking agent before the Iobenguane I-123 Injection, AdreView, scan unless medically not indicated, according to local practice.; Other Names: Potassium Iodide; Potassium Perchlorate; Lugol's Solution; Device: Implantable Cardioverter Defibrillator; All participants allocated to the SoC (control) group underwent ICD implantation.
EXPERIMENTAL: Standard of Care; Participants 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.	Drug: Iobenguane I -123 Injection; Iobenguane I-123 Injection, AdreView. All participants scheduled for an Iobenguane I-123 Injection, AdreView scan.; Other Names: AdreView; Iobenguane I-123 Injection; Device: Implantable Cardioverter Defibrillator; In the Iobenguane I-123 Injection group, participants with H/M ratio less or equal to 1.6 underwent ICD device implantation, while those with H/M ratio greater than or equal to 1.6 did not undergo ICD implantation.; Device: Implantable Cardioverter Defibrillator; All participants allocated to the SoC (control) group underwent ICD implantation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause Mortality	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.	From randomization until the end of the follow-up period (median 304 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Events of Complications of Device: H/M >=1.6 in Full Analysis Set	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.	From randomization until the end of the follow-up period (median 304 days)
Percentage of Participants With Cardiac Death	Cardiac death composed of sudden cardiac death, death due to cardiac arrhythmia, death due to heart failure, and death due to other cardiovascular causes.	From randomization until the end of the follow-up period (median 304 days)
Percentage of Participants With Hospitalization for Cardiovascular Cause	Percentage of participants who were hospitalized for cardiovascular cause were reported.	From randomization until the end of the follow-up period (median 304 days)
Percentage of Participants With All-Cause Hospitalization	Percentage of participants with all-cause hospitalization were reported.	From randomization until the end of the follow-up period (median 304 days)
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)	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.	From randomization until the end of the follow-up period (median 304 days)
Percentage of Participants With Syncope	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.	From randomization until the end of the follow-up period (median 304 days)
Percentage of Participants With Implantable Cardioverter Defibrillator (ICD) Implantation	Percentage of participants with ICD implantation were reported.	From randomization until the end of the follow-up period (median 304 days)
Percentage of Participants With Events of Complications of Device	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'.	From randomization until the end of the follow-up period (median 304 days)

Collaborators and Investigators

• Sponsor: GE Healthcare
• Collaborators: ABX CRO; H2O Clinical LLC; TransPerfect; Advanced Clinical, LLC; TFS; AG Mednet Inc.; ICON CEAC; ICON Clinical

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 30, 2015
• Primary Completion (ACTUAL): May 4, 2018
• Study Completion (ACTUAL): May 4, 2018

Study Registration Dates

• First Submitted: January 7, 2016
• First Submitted That Met QC Criteria: January 12, 2016
• First Posted (ESTIMATE): January 14, 2016

Study Record Updates

• Last Update Posted (ACTUAL): May 22, 2019
• Last Update Submitted That Met QC Criteria: April 26, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Implantable cardioverter defibrillator (ICD); All-cause mortality; Heart Failure (HF); Single photon emission computer tomography scan (SPECT); Left Ventricular ejection fraction (LVEF); New York Health Association (NYHA); Metaiodobenzylguanidine (mIBG); 123I-iobenguane; Heart-to-mediastinal ratio (H/M); ADMIRE-ICD (AdreView Myocardial Imaging for Risk Evaluation - Implantable Cardioverter Defibrillator; Cardiac mortality
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Radiopharmaceuticals; Hemostatics; Coagulants; 3-Iodobenzylguanidine; Lugol's solution
• Other Study ID Numbers: GE-122-020; 2015-001464-19 (EUDRACT_NUMBER)