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
Condition: Heart Failure
MeSH terms: Heart Failure
Intervention: Iobenguane I -123 Injection; Implantable Cardioverter Defibrillator; Thyroid blocking; Iobenguane I -123 Injection; Implantable Cardioverter Defibrillator
Intervention description: Iobenguane I-123 Injection, AdreView. All participants scheduled for an Iobenguane I-123 Injection, AdreView scan.; 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.; 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, AdreView. All participants scheduled for an Iobenguane I-123 Injection, AdreView scan.; All participants allocated to the SoC (control) group underwent ICD implantation.
Intervention MeSH terms: 3-Iodobenzylguanidine; Lugol's solution
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 395.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
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

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.
    

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.