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

NCT ID: NCT02656329

Last Updated: 2019-05-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 395 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-30
• Study Completion Date: 2018-05-04

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.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Iobenguane I -123 Injection

Intervention Type: DRUG

Iobenguane I-123 Injection, AdreView. All participants scheduled for an Iobenguane I-123 Injection, AdreView scan.

Implantable Cardioverter Defibrillator

Intervention Type: DEVICE

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.

Thyroid blocking

Intervention Type: DRUG

Participants received a thyroid blocking agent before the Iobenguane I-123 Injection, AdreView, scan unless medically not indicated, according to local practice.

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.

Group Type: EXPERIMENTAL

Iobenguane I -123 Injection

Intervention Type: DRUG

Iobenguane I-123 Injection, AdreView. All participants scheduled for an Iobenguane I-123 Injection, AdreView scan.

Implantable Cardioverter Defibrillator

Intervention Type: DEVICE

All participants allocated to the SoC (control) group underwent ICD implantation.

Interventions

Iobenguane I -123 Injection

Iobenguane I-123 Injection, AdreView. All participants scheduled for an Iobenguane I-123 Injection, AdreView scan.

Intervention Type: DRUG

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.

Intervention Type: DEVICE

Thyroid blocking

Participants received a thyroid blocking agent before the Iobenguane I-123 Injection, AdreView, scan unless medically not indicated, according to local practice.

Intervention Type: DRUG

Iobenguane I -123 Injection

Iobenguane I-123 Injection, AdreView. All participants scheduled for an Iobenguane I-123 Injection, AdreView scan.

Intervention Type: DRUG

Implantable Cardioverter Defibrillator

All participants allocated to the SoC (control) group underwent ICD implantation.

Intervention Type: DEVICE

Other Intervention Names

AdreView; Iobenguane I-123 Injection; Potassium Iodide; Potassium Perchlorate; Lugol's Solution; AdreView; Iobenguane I-123 Injection

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Advanced Clinical, LLC

UNKNOWN

Sponsor Role: collaborator

TFS

UNKNOWN

Sponsor Role: collaborator

H2O Clinical LLC

INDUSTRY

Sponsor Role: collaborator

AG Mednet Inc.

UNKNOWN

Sponsor Role: collaborator

ICON CEAC

UNKNOWN

Sponsor Role: collaborator

ICON Clinical

UNKNOWN

Sponsor Role: collaborator

ABX CRO

OTHER

Sponsor Role: collaborator

TransPerfect

INDUSTRY

Sponsor Role: collaborator

GE Healthcare

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Vascular Biology and Hypertension Program, University of Alabama at Birmingham

Birmingham, Alabama, United States

Comprehensive Cardiovascular Medical Group

Bakersfield, California, United States

Sharp Grossmont Hospital

La Mesa, California, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

VA Connecticut Healthcare System (VACHS)

West Haven, Connecticut, United States

Cardiology Physicians PA/Red Clay Research, LLC

Newark, Delaware, United States

Bethesda Health

Boynton Beach, Florida, United States

University of Florida Health Jacksonville

Jacksonville, Florida, United States

University of Miami Hospital

Miami, Florida, United States

Cardiology Consultants

Pensacola, Florida, United States

South Miami Heart Specialists

South Miami, Florida, United States

Tampa General Hospital

Tampa, Florida, United States

University of South Florida

Tampa, Florida, United States

Augusta University

Augusta, Georgia, United States

Rush University Medical Center

Chicago, Illinois, United States

Northwestern University

Evanston, Illinois, United States

MMP ME Health Cardiology

Scarborough, Maine, United States

MedStar Shah Medical Group

Charlotte Hall, Maryland, United States

Boston Medical Center

Boston, Massachusetts, United States

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

Detroit, Michigan, United States

Regions Hospital and Regions Heart Center Clinic

Saint Paul, Minnesota, United States

University at Buffalo

Buffalo, New York, United States

Advanced Cardiology Group

Buffalo, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

WakeMed

Raleigh, North Carolina, United States

Veterans Affairs North Texas Healthcare System

Dallas, Texas, United States

Houston Methodist Hospital

Houston, Texas, United States

Texas Institute of Cardiology, PA

McKinney, Texas, United States

Victoria Heart and Vascular Center

Victoria, Texas, United States

University of Calgary

Calgary, Alberta, Canada

Royal Alexandra Hospital

Edmonton, Alberta, Canada

London Health Sciences Centre

London, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Montreal Heart Institute

Montreal, Quebec, Canada

CIUSSS de L'Estrie - CHUS Hopital Fleurimont

Sherbrooke, Quebec, Canada

Institut Universitaire De Cardiologie Et De Pneumologie De Quebec

Québec, , Canada

Fakultni nemocnice Brno Bohunice

Brno, , Czechia

Fakultni nemocnice u sv. Anny v Brne

Brno, , Czechia

FN Hradec Kralove

Hradec Králové, , Czechia

Krajska nemocnice Liberec

Liberec, , Czechia

Fakultni nemocnice Plzen

Lochotín, , Czechia

Fakultni nemocnice v Kralovske Vinohrady

Prague, , Czechia

Fakultni nemocnice v Motole

Prague, , Czechia

Masarykova nemocnice v Usti nad Labem

Ústí nad Labem, , Czechia

CHR Metz-Thionville - Site de Mercy

Ars-Laquenexy, , France

CH Antoine Beclere

Clamart, , France

CHU Clermont-Ferrand, 63003 Montalembert

Clermont-Ferrand, , France

CHU Henri Mondor

Créteil, , France

CHRU de Lille

Lille, , France

Hopital de Rangueil CHU Toulouse

Toulouse, , France

Clinique Pasteur

Toulouse, , France

Hopitaux de Brabois Chu Nancy

Vandœuvre-lès-Nancy, , France

Kliniken Maria Hilf GmbH, Klinik fur Nuklearmedizin

Mönchengladbach, , Germany

Klinik & Poliklinik fur Nuklearmedizin, LMU, Campus Grobhader

Munich, , Germany

Varosmajori Sziv es Ergyogyaszati Klinika

Budapest, , Hungary

Budai Irgalmasrendi Korhaz

Budapest, , Hungary

Gottsegen Gyorgy Orszagos Kardiologiai Intezet

Budapest, , Hungary

Magyar Honvedseg Egeszsegugyi Kozpont Kardiológia Osztály/Nuklearis Medicina Osztaly

Budapest, , Hungary

Semmelweis Egyetem Nuklearis Medicina Kozpont

Budapest, , Hungary

Debreceni Egyetem, Kardiologia Intezet and ScanoMed Nuclear Medicine Institute

Debrecen, , Hungary

Coromed-SMO ft.

Pécs, , Hungary

Azienda Ospedaliera Universitaria G. Martino

Messina, , Italy

Area Cardiologia Critica - IRCCS Centro Cardiologico Mozino

Milan, , Italy

Ospedale Santa Croce

Moncalieri, , 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

Instituti Clinici Scientifici Maugeri Spa Societa Benefit

Pavia, , Italy

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

Rome, , Italy

Ospedale Santa Maria di Ca' Foncello

Treviso, , Italy

Venezia Mestre - Azienda ULSS 12 "Veneziana"

Venezia, , Italy

Ospedale dell'Angelo, 30174, Venezia Mestre

Venice, , Italy

Onze Lieve Vrouwen Gasthuis

Amsterdam, , Netherlands

Academic Medical Center

Amsterdam, , Netherlands

Amphia Zickenhuis

Breda, , Netherlands

Leiden University Medical Center

Leiden, , Netherlands

Maastricht University Medical Center

Maastricht, , Netherlands

Uniwersytecki Szpital Kliniczny w Bialymstoku

Bialystok, , Poland

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Samodzielny Publiczny Szpital Kliniczny Nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach

Katowice, , 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

Wroclaw, , Poland

Hospital Clinico Universitario Virgen de la Arrixaca

El Palmar (Murcia), , Spain

Hospital Universitario Virgen de las Nieves

Granada, , 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

Málaga, , Spain

Hospital Universitario Son Espases

Palma de Mallorca (Illes Balears), , Spain

Hospital Clínico de Salamanca

Salamanca, , 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

Countries

United States; Canada; Czechia; France; Germany; Hungary; Italy; Netherlands; Poland; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-001464-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GE-122-020

Identifier Type: -

Identifier Source: org_study_id