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

NCT02656329 | Terminated Phase 3 Results DMC

• 2 other identifiers: GE-122-0202015-001464-19
• Study Type: interventional
• Target: 395
• Locations: 10 countries
• Sites: 94

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

Keywords

Heart Failure (HF); Single photon emission computer tomography scan (SPECT); Implantable cardioverter defibrillator (ICD); 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; All-cause mortality; Cardiac mortality

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Percentage of Participants With Events of Complications of Device: H/M >=1.6 in Full Analysis Set

  From randomization until the end of the follow-up period (median 304 days)

• Percentage of Participants With Cardiac Death

  From randomization until the end of the follow-up period (median 304 days)

• Percentage of Participants With Hospitalization for Cardiovascular Cause

  From randomization until the end of the follow-up period (median 304 days)

• Percentage of Participants With All-Cause Hospitalization

  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)

  From randomization until the end of the follow-up period (median 304 days)

Study Arms (2)

AdreView™

EXPERIMENTAL

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; Device: Implantable Cardioverter Defibrillator; Drug: Thyroid blocking

Standard of Care

EXPERIMENTAL

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; Device: Implantable Cardioverter Defibrillator

Interventions

Iobenguane I -123 Injection DRUG

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

Also known as: AdreView, Iobenguane I-123 Injection

AdreView™

Implantable Cardioverter Defibrillator 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.

AdreView™

Thyroid blocking DRUG

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

Also known as: Potassium Iodide, Potassium Perchlorate, Lugol's Solution

AdreView™

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• %≤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 \[Simpson's or multidisc method only, M-mode echocardiography was not accepted\].
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GE Healthcare: lead
• Advanced Clinical, LLC: collaborator
• TFS: collaborator
• H2O Clinical LLC: collaborator
• AG Mednet Inc.: collaborator
• ICON CEAC: collaborator
• ICON Clinical: collaborator
• ABX CRO: collaborator
• TransPerfect: collaborator

Study Sites (94)

Vascular Biology and Hypertension Program, University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Comprehensive Cardiovascular Medical Group

Bakersfield, California, 93309, United States

Location

Sharp Grossmont Hospital

La Mesa, California, 91942, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

VA Connecticut Healthcare System (VACHS)

West Haven, Connecticut, 06516, United States

Location

Cardiology Physicians PA/Red Clay Research, LLC

Newark, Delaware, 19713, United States

Location

Bethesda Health

Boynton Beach, Florida, 33435, United States

Location

University of Florida Health Jacksonville

Jacksonville, Florida, 32209, United States

Location

University of Miami Hospital

Miami, Florida, 33136, United States

Location

Cardiology Consultants

Pensacola, Florida, 32501, United States

Location

South Miami Heart Specialists

South Miami, Florida, 33143, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

University of South Florida

Tampa, Florida, 33609, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Northwestern University

Evanston, Illinois, 60208, United States

Location

MMP ME Health Cardiology

Scarborough, Maine, 04074, United States

Location

MedStar Shah Medical Group

Charlotte Hall, Maryland, 20622, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

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

Detroit, Michigan, 48202, United States

Location

Regions Hospital and Regions Heart Center Clinic

Saint Paul, Minnesota, 55101, United States

Location

University at Buffalo

Buffalo, New York, 14203, United States

Location

Advanced Cardiology Group

Buffalo, New York, 14215, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

WakeMed

Raleigh, North Carolina, 27610, United States

Location

Veterans Affairs North Texas Healthcare System

Dallas, Texas, 75216, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Institute of Cardiology, PA

McKinney, Texas, 75071, United States

Location

Victoria Heart and Vascular Center

Victoria, Texas, 77901, United States

Location

University of Calgary

Calgary, Alberta, T2N 1N4, Canada

Location

Royal Alexandra Hospital

Edmonton, Alberta, T5H3V9, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

CIUSSS de L'Estrie - CHUS Hopital Fleurimont

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Institut Universitaire De Cardiologie Et De Pneumologie De Quebec

Québec, G1V 4G5, Canada

Location

Fakultni nemocnice Brno Bohunice

Brno, 625 00, Czechia

Location

Fakultni nemocnice u sv. Anny v Brne

Brno, 656 91, Czechia

Location

FN Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Krajska nemocnice Liberec

Liberec, 460 63, Czechia

Location

Fakultni nemocnice Plzen

Lochotín, 304 60, Czechia

Location

Fakultni nemocnice v Kralovske Vinohrady

Prague, 100 34, Czechia

Location

Fakultni nemocnice v Motole

Prague, 150 06, Czechia

Location

Masarykova nemocnice v Usti nad Labem

Ústí nad Labem, 40001, Czechia

Location

CHR Metz-Thionville - Site de Mercy

Ars-Laquenexy, 57530, France

Location

CH Antoine Beclere

Clamart, 92140, France

Location

CHU Clermont-Ferrand, 63003 Montalembert

Clermont-Ferrand, France

Location

CHU Henri Mondor

Créteil, 94010, France

Location

CHRU de Lille

Lille, 59037, France

Location

Hopital de Rangueil CHU Toulouse

Toulouse, 31059, France

Location

Clinique Pasteur

Toulouse, 31300, France

Location

Hopitaux de Brabois Chu Nancy

Vandœuvre-lès-Nancy, 54511, France

Location

Kliniken Maria Hilf GmbH, Klinik fur Nuklearmedizin

Mönchengladbach, 41063, Germany

Location

Klinik & Poliklinik fur Nuklearmedizin, LMU, Campus Grobhader

Munich, Germany

Location

Varosmajori Sziv es Ergyogyaszati Klinika

Budapest, 1112, Hungary

Location

Budai Irgalmasrendi Korhaz

Budapest, H-1023, Hungary

Location

Gottsegen Gyorgy Orszagos Kardiologiai Intezet

Budapest, H-1134, Hungary

Location

Magyar Honvedseg Egeszsegugyi Kozpont Kardiológia Osztály/Nuklearis Medicina Osztaly

Budapest, H-1134, Hungary

Location

Semmelweis Egyetem Nuklearis Medicina Kozpont

Budapest, Hungary

Location

Debreceni Egyetem, Kardiologia Intezet and ScanoMed Nuclear Medicine Institute

Debrecen, 4032, Hungary

Location

Coromed-SMO ft.

Pécs, H-7623, Hungary

Location

Azienda Ospedaliera Universitaria G. Martino

Messina, 98125, Italy

Location

Area Cardiologia Critica - IRCCS Centro Cardiologico Mozino

Milan, 20138, Italy

Location

Ospedale Santa Croce

Moncalieri, 10024, Italy

Location

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

Napoli, 80131, Italy

Location

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

Novara, 28100, Italy

Location

Instituti Clinici Scientifici Maugeri Spa Societa Benefit

Pavia, 27100, Italy

Location

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

Rome, 00161, Italy

Location

Ospedale Santa Maria di Ca' Foncello

Treviso, 31100, Italy

Location

Venezia Mestre - Azienda ULSS 12 "Veneziana"

Venezia, 30174, Italy

Location

Ospedale dell'Angelo, 30174, Venezia Mestre

Venice, Italy

Location

Onze Lieve Vrouwen Gasthuis

Amsterdam, 1091 AC, Netherlands

Location

Academic Medical Center

Amsterdam, 1105 AZ, Netherlands

Location

Amphia Zickenhuis

Breda, 4818 CK, Netherlands

Location

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

Location

Maastricht University Medical Center

Maastricht, 6229 HX, Netherlands

Location

Uniwersytecki Szpital Kliniczny w Bialymstoku

Bialystok, 15-276, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-952, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach

Katowice, 40-635, Poland

Location

Krakowski Szpital Specjalistyczny im. Jana Pawla II

Krakow, 31-202, Poland

Location

Wojskowy Instytut Medyczny

Warsaw, 04-141, Poland

Location

Samodzielny Publiczny Centralny Szpital Kliniczny

Warsaw, Poland

Location

Dolnośląski Szpital Specjalistyczny im. T. Marciniaka Centrum Medycyny Ratunkowej

Wroclaw, 54-049, Poland

Location

Hospital Clinico Universitario Virgen de la Arrixaca

El Palmar (Murcia), 30120, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, 18014, Spain

Location

Hospital Universitario de Leon

León, 24071, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico Universitario San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Universitario Son Espases

Palma de Mallorca (Illes Balears), 07120, Spain

Location

Hospital Clínico de Salamanca

Salamanca, 37002, Spain

Location

Hospital Universitario San Juan de Alicante

San Juan Alicante, 03550, Spain

Location

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela (A Coruña), 15706, Spain

Location

Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

MeSH Terms

Conditions

Heart Failure

Interventions

3-Iodobenzylguanidine; Defibrillators, Implantable; thyroid stimulation-blocking antibody; Potassium Iodide; potassium perchlorate; Lugol's solution

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Iodobenzenes; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Hydrocarbons, Iodinated; Hydrocarbons, Halogenated; Defibrillators; Electrodes; Electrical Equipment and Supplies; Equipment and Supplies; Electrodes, Implanted; Prostheses and Implants; Iodides; Iodine Compounds; Inorganic Chemicals; Potassium Compounds

Limitations and Caveats

The study was early terminated by sponsor after enrollment of 395 participants due to very slow recruitment rates. Sample size was 395 participants instead of planned 2354 participants.

Results Point of Contact

• Title: Francois Tranquart, M.D., Ph.D.
• Organization: GE Healthcare

francois.tranquart@ge.com

0-44-1494-543037

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2016
• First Posted: January 14, 2016
• Study Start: December 30, 2015
• Primary Completion: May 4, 2018
• Study Completion: May 4, 2018
• Last Updated: May 22, 2019
• Results First Posted: May 22, 2019

Record last verified: 2019-04

Locations

US (29); PL (7); DE (2); ES (11); IT (10); FR (8); CZ (8); HU (7); CA (7); NL (5)