Open-label, Test-retest Study Assessing Reproducibility of Quantitative Measurements of Myocardial Uptake of AdreView.

Study Overview
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Brief Summary
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The aim of the study was to assess the reproducibility of quantitative measurements of myocardial uptake of Iobenguane I 123 on planar and single photon emission computed tomography (SPECT) imaging following intravenous (i.v.) administration of AdreView. Efficacy was assessed based upon the absolute differences between quantitative analyses of imaging data on 2 scans performed 5 to 14 days apart.

Official Title
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A Phase 4, Open-label Test-retest Study to Assess the Reproducibility of Quantitative Measurements of Myocardial Uptake of AdreView (Iobenguane I 123 Injection)

Conditions
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Heart Failure (HF), Ventricular Dysfunction, Left

Intervention / Treatment
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* Drug: AdreView (Iobenguane I 123 Injection)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant was originally diagnosed with New York Heart Association (NYHA) Class II-III HF due to ischemic heart disease at least 3 months or due to non-ischemic cardiomyopathy at least 6 months before enrollment into the study. The participant had Left Ventricular (LV) dysfunction with Left Ventricular Ejection Fraction (LVEF) less than or equal to 35% measured by an appropriate method (e.g., radionuclide or contrast ventriculography, electrocardiogram [ECG]-gated SPECT myocardial perfusion imaging [MPI], magnetic resonance [MR] imaging, computed tomography [CT] or echocardiography) within 6 months of enrollment into the study and documented in the participant's medical record. The participant had a history of compliance with prescribed heart failure (HF) medications and took HF guidelines-based medication at study entry including at a minimum a beta-blocker and either an angiotensin converting enzyme inhibitor or angiotensin receptor antagonist unless documented to be intolerant to any of these classes of medications. The participant had been on a stable medical regimen for a minimum of 3 months, with no hospitalizations or change in HF medications or HF symptoms. Participants must be clinically stable for at least 7 days before enrolling into the study (e.g., not experiencing continuing chest pain or hemodynamic instability). Exclusion Criteria: The participant had previously received 123 I-mIBG or 131 I-mIBG. The participant had known or suspected hypersensitivity/allergy to iodine, Iobenguane or to any of the excipients in AdreView. The participant had a heart transplant at any time prior to enrollment. The participant had LVEF >35% as measured by an appropriate method (e.g., radionuclide or contrast ventriculography, ECG-gated SPECT MPI, MR, CT, or echocardiography) within 30 days prior to enrollment into the study. The participant had received defibrillation either external or via an implantable cardioverter defibrillator (ICD), anti-tachycardia pacing, or cardioversion to treat an arrhythmic event in the previous 90 days. The participant had a cardiac revascularization, insertion of an ICD, or acute myocardial infarction within 30 days before study entry. The participant used any of the following medications: Amitriptyline and derivatives, imipramine and derivatives, other antidepressants that inhibit the norepinephrine transporter, antihypertensives that deplete norepinephrine stores or inhibit reuptake, sympathomimetic amines and cocaine. The participant had either NYHA Class I or NYHA Class IV HF at the time of study entry. The participant had renal insufficiency (creatinine >3 mg/dl). The participant had participated in a clinical trial involving IMP or devices within 30 days prior to first administration of AdreView™. In the investigator's opinion, the participant's medical history included either extensive lifetime exposure to ionizing radiation (medical, occupational, other) or documented total radiation dose >50 mSv during the previous 5 years. The participant had experienced HF hospitalization, increased HF symptoms without hospitalization, or had a change or increase in HF medications during the previous 3 months. The participant had a serious non-cardiac medical condition associated with significant elevation of plasma catecholamines, including pheochromocytoma.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AdreView (Iobenguane I 123 Injection)<br>Two administrations of single intravenous (i.v) injection of Iobenguane I 123 10 millicuries (mCi) (370 MBq) over 1 to 2 minutes within an interval of 5 to 14 days. | Drug: AdreView (Iobenguane I 123 Injection)<br>* AdreView 10 mCi as a single i.v administration<br>* Other names: meta-iodobenzylguanidine (123 I-mIBG);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Assess Test-retest Reproducibility of Iobenguane I 123 Injection Myocardial Uptake in Heart Failure (HF) Participants on Planar Imaging at 3 Hours 50 Minutes Following I.V. Injection of AdreView (Iobenguane I 123 Injection) | Participants underwent 2 AdreView (Iobenguane I 123 Injection) exams on the same gamma camera within 5 to 14 days, with the requirement that there was no change in the clinical condition of the participant or in the imaging equipment between the 2 procedures. Each imaging study was processed and read independently by 3 technologists. Mean heart/mediastinum (H/M) ratio difference (with 95% confidence interval [CI]) was used as the measure of test stability. | 3 Hours 50 Minutes post administration of 2 dosing within an interval of 5 to 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Assess the Test-retest Reproducibility of Iobenguane I 123 Injection Myocardial Uptake on Planar Imaging at 15 Minutes Following Administration of AdreView (Iobenguane I 123 Injection) | Measurements of H/M ratio and the extent of difference between H/M measurements following AdreView administration and 15 minutes delayed planar imaging on 2 separate days within an interval of 5 to 14 days, was used to assess the test-retest reproducibility. Data from test-retest study was used to estimate the normal ranges for variation in quantitation of myocardial tracer uptake using AdreView. H/M ratios were calculated by 3 technologists and average of 3 technologists was calculated based on non-missing technologists reviewing results. All non-missing technologist evaluations were averaged per participant. | 15 minutes post administration of 2 dosing within an interval of 5 to 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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myocardial uptake, SPECT imaging, planar imaging, AdreView™, Nuclear imaging, Radiopharmaceutical, Iobenguane, I-123, reproducibility, Quantitative measurements