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

Heart Failure Clinical Trial

— ADMIRE-ICD  

Official title:

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%

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02656329
• Other study ID #: GE-122-020
• Secondary ID: 2015-001464-19
• Status: Terminated
• Phase: Phase 3
• Start date: December 30, 2015
• Est. completion date: May 4, 2018

Study information

• Verified date: April 2019
• Source: GE Healthcare
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 395
• Est. completion date: May 4, 2018
• Est. primary completion date: May 4, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure

Intervention

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

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

Device:
• Implantable Cardioverter Defibrillator
All participants allocated to the SoC (control) group underwent ICD implantation.

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	Royal Alexandra Hospital	Edmonton	Alberta
Canada	London Health Sciences Centre	London	Ontario
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	Institut Universitaire De Cardiologie Et De Pneumologie De Quebec	Quebec
Canada	CIUSSS de L'Estrie - CHUS Hopital Fleurimont	Sherbrooke	Quebec
Canada	St. Michael's Hospital	Toronto	Ontario
Czechia	Fakultni nemocnice Brno Bohunice	Brno
Czechia	Fakultni nemocnice u sv. Anny v Brne	Brno
Czechia	FN Hradec Kralove	Hradec Kralove
Czechia	Krajska nemocnice Liberec	Liberec
Czechia	Fakultni nemocnice Plzen	Lochotín
Czechia	Fakultni nemocnice v Kralovske Vinohrady	Praha 10
Czechia	Fakultni nemocnice v Motole	Praha 5
Czechia	Masarykova nemocnice v Usti nad Labem	Usti nad Labem
France	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	Clinique Pasteur	Toulouse
France	Hopital de Rangueil CHU Toulouse	Toulouse Cedex 9
France	Hopitaux de Brabois Chu Nancy	Vandoeuvre Les Nancy Cedex
Germany	Kliniken Maria Hilf GmbH, Klinik fur Nuklearmedizin	Monchengladbach
Germany	Klinik & Poliklinik fur Nuklearmedizin, LMU, Campus Grobhader	Munich
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	Varosmajori Sziv es Ergyogyaszati Klinika	Budapest
Hungary	Debreceni Egyetem, Kardiologia Intezet and ScanoMed Nuclear Medicine Institute	Debrecen
Hungary	Coromed-SMO ft.	Pécs
Italy	Azienda Ospedaliera Universitaria G. Martino	Messina
Italy	Area Cardiologia Critica - IRCCS Centro Cardiologico Mozino	Milano
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
Netherlands	Academic Medical Center	Amsterdam
Netherlands	Onze Lieve Vrouwen Gasthuis	Amsterdam
Netherlands	Amphia Zickenhuis	Breda
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Maastricht University Medical Center	Maastricht
Poland	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	Samodzielny Publiczny Centralny Szpital Kliniczny	Warsaw
Poland	Wojskowy Instytut Medyczny	Warsaw
Poland	Dolnoslaski Szpital Specjalistyczny im. T. Marciniaka Centrum Medycyny Ratunkowej	Wroclaw
Spain	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 Clinico Universitario San Carlos	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Malaga
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
United States	Augusta University	Augusta	Georgia
United States	Comprehensive Cardiovascular Medical Group	Bakersfield	California
United States	Vascular Biology and Hypertension Program, University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston Medical Center	Boston	Massachusetts
United States	Bethesda Health	Boynton Beach	Florida
United States	Montefiore Medical Center	Bronx	New York
United States	Advanced Cardiology Group	Buffalo	New York
United States	University at Buffalo	Buffalo	New York
United States	MedStar Shah Medical Group	Charlotte Hall	Maryland
United States	Rush University Medical Center	Chicago	Illinois
United States	Veterans Affairs North Texas Healthcare System	Dallas	Texas
United States	Department of Cardiology, K-14 (Henry Ford Health System)	Detroit	Michigan
United States	Northwestern University	Evanston	Illinois
United States	Houston Methodist Hospital	Houston	Texas
United States	University of Florida Health Jacksonville	Jacksonville	Florida
United States	Sharp Grossmont Hospital	La Mesa	California
United States	Texas Institute of Cardiology, PA	McKinney	Texas
United States	University of Miami Hospital	Miami	Florida
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Cardiology Physicians PA/Red Clay Research, LLC	Newark	Delaware
United States	Cardiology Consultants	Pensacola	Florida
United States	WakeMed	Raleigh	North Carolina
United States	Regions Hospital and Regions Heart Center Clinic	Saint Paul	Minnesota
United States	MMP ME Health Cardiology	Scarborough	Maine
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	Victoria Heart and Vascular Center	Victoria	Texas
United States	VA Connecticut Healthcare System (VACHS)	West Haven	Connecticut

Sponsors (9)

Lead Sponsor	Collaborator
GE Healthcare	ABX CRO, Advanced Clinical, LLC, AG Mednet Inc., H2O Clinical LLC (now Firma Clinical Research), ICON CEAC, ICON Clinical, TFS, TransPerfect

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)