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

• Sponsor: GE Healthcare (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01936649
• Collaborator: H2O Clinical LLC (Industry), Quintiles, Inc. (Industry)
• Enrollment: 63
• Location: 1
• Arm: 1
• Duration (Months): 6
• Patients Per Site Per Month: 10.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure (HF); Ventricular Dysfunction, Left	Drug: AdreView (Iobenguane I 123 Injection)	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Phase 4, Open-label Test-retest Study to Assess the Reproducibility of Quantitative Measurements of Myocardial Uptake of AdreView (Iobenguane I 123 Injection)
• Study Start Date: Aug 1, 2013
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AdreView (Iobenguane I 123 Injection) 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); AdreView 10 mCi as a single i.v administration; Other Names: meta-iodobenzylguanidine (123 I-mIBG)

Outcome Measures

Primary Outcome Measures

1. 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) [3 Hours 50 Minutes post administration of 2 dosing within an interval of 5 to 14 days]

   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.

Secondary Outcome Measures

1. 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) [15 minutes post administration of 2 dosing within an interval of 5 to 14 days]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GE Healthcare	Princeton	New Jersey	United States	08540

Sponsors and Collaborators

• GE Healthcare
• H2O Clinical LLC
• Quintiles, Inc.

Investigators

• Study Chair: Arnold Jacobson, M.D., GE Healthcare

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GE Healthcare
• ClinicalTrials.gov Identifier: NCT01936649
• Other Study ID Numbers: GE-122-015
• First Posted: Sep 6, 2013
• Last Update Posted: Dec 8, 2016
• Last Verified: Oct 1, 2016

• Keywords provided by GE Healthcare: Nuclear imaging; Radiopharmaceutical; Iobenguane; I-123; reproducibility; Quantitative measurements; myocardial uptake; SPECT imaging; planar imaging; AdreView™
• Additional relevant MeSH terms: Ventricular Dysfunction; Ventricular Dysfunction, Left; 3-Iodobenzylguanidine

Study Results

Participant Flow

Recruitment Details	The study was conducted at 10 centers in US. A total of 63 participants were enrolled in the study between 16 August 2013 and 20 February 2014.
Pre-assignment Detail	Out of 63 enrolled participants, 51 received at least 1 administration of AdreView (Iobenguane I 123 injection) and 50 participants received 2 administrations of AdreView. Myocardial AdreView uptake over time was quantitatively measured via planar and single photon emission computed tomography (SPECT) imaging at various time points post-injection.

Arm/Group Title	AdreView (Iobenguane I 123 Injection)
Arm/Group Description	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.
Period Title: Overall Study
STARTED	63
Treated	51
COMPLETED	50
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	AdreView (Iobenguane I 123 Injection)
Arm/Group Description	Two administrations of single i.v. injection of Iobenguane I 123 10 mCi (370 MBq) over 1 to 2 minutes within an interval of 5 to 14 days.
Overall Participants	51
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.2 (12.46)
Sex: Female, Male (Count of Participants)
Female	8 15.7%
Male	43 84.3%
Region of Enrollment (participants) [Number]
United States	51 100%
Safety Assessment (participants) [Number]
Number [participants]	51 100%

Outcome Measures

1. Primary Outcome

Title	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)
Description	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.
Time Frame	3 Hours 50 Minutes post administration of 2 dosing within an interval of 5 to 14 days

Outcome Measure Data

Analysis Population Description

Efficacy population that included all participants who underwent 2 administrations of AdreView (Iobenguane I 123 Injection); had at least an interpretable planar image acquisition at 3 hours 50 minutes post-injection after each AdreView administration. Here, 'n' signifies number of participants analyzed by the technologist.

Arm/Group Title	AdreView (Iobenguane I 123 Injection)
Arm/Group Description	Two administrations of single i.v. injection of Iobenguane I 123 10 mCi (370 MBq) over 1 to 2 minutes within an interval of 5 to 14 days.
Measure Participants	47
Technologist A (post dosing-1) (n=46)	1.435 (0.2238)
Technologist A (post dosing-2) (n=47)	1.422 (0.2229)
Technologist A(Dosings:absolute difference) (n=46)	0.070 (0.0612)
Technologist B (post dosing-1) (n=47)	1.430 (0.220)
Technologist B (post dosing-2) (n=47)	1.436 (0.2069)
Technologist B(Dosings:absolute difference) (n=47)	0.060 (0.0413)
Technologist C (post dosing-1) (n=47)	1.427 (0.2115)
Technologist C (post dosing-2) (n=47)	1.441 (0.1945)
Technologist C(Dosings:absolute difference) (n=47)	0.067 (0.0537)
Average (post dosing-1) (n=47)	1.429 (0.2160)
Average (post dosing-2) (n=47)	1.433 (0.2048)
Average (Dosings:absolute difference) (n=47)	0.065 (0.0348)

2. Secondary Outcome

Title	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)
Description	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.
Time Frame	15 minutes post administration of 2 dosing within an interval of 5 to 14 days

Outcome Measure Data

Analysis Population Description

Efficacy population that included all participants who underwent 2 administrations of AdreView; had at least an interpretable planar image acquisition at 15 minutes post-injection after each AdreView administration. Here, 'n' signifies number of participants analyzed by the technologist.

Arm/Group Title	AdreView (Iobenguane I 123 Injection)
Arm/Group Description	Two administrations of single i.v. injection of Iobenguane I 123 10 mCi (370 MBq) over 1 to 2 minutes within an interval of 5 to 14 days.
Measure Participants	47
Technologist A (post dosing-1) (n=47)	1.584 (0.2258)
Technologist A (post dosing-2) (n=47)	1.567 (0.2267)
Technologist A(Dosings:absolute difference) (n=47)	0.081 (0.0765)
Technologist B (post dosing-1) (n=47)	1.568 (0.2262)
Technologist B (post dosing-2) (n=47)	1.553 (0.2169)
Technologist B(Dosings:absolute difference) (n=47)	0.062 (0.0532)
Technologist C (post dosing-1) (n=47)	1.593 (0.2227)
Technologist C (post dosing-2) (n=47)	1.571 (0.2203)
Technologist C(Dosing:absolute difference) (n=47)	0.071 (0.0541)
Average (post dosing-1) (n=47)	1.581 (0.2212)
Average (post dosing-2) (n=47)	1.564 (0.2195)
Average (Dosings:absolute difference) (n=47)	0.072 (0.0485)

Adverse Events

Time Frame	From Baseline up to discharge from hospital on each dosing.
Adverse Event Reporting Description	Adverse events (AEs) reported were treatment emergent adverse events (TEAEs) that were AEs that begins (or a pre-existing AE that worsens) after receiving investigational medicinal product through the time of discharge on each dosing day.
Arm/Group Title	AdreView (Iobenguane I 123 Injection)
Arm/Group Description	Two administrations of single i.v. injection of Iobenguane I 123 10 mCi (370 MBq) over 1 to 2 minutes within an interval of 5 to 14 days.
All Cause Mortality
	AdreView (Iobenguane I 123 Injection)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	AdreView (Iobenguane I 123 Injection)
	Affected / at Risk (%)	# Events
Total	0/51 (0%)
Other (Not Including Serious) Adverse Events
	AdreView (Iobenguane I 123 Injection)
	Affected / at Risk (%)	# Events
Total	0/51 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI and/or institution is that the Sponsor can review results communications prior to public release and can restrict communications regarding trial results for a period that is more than 30 days (publications/abstracts) but not to exceed 90 days (patent related issues) from the time submitted to the Sponsor to review. The PI may be asked to remove any Sponsor confidential information and/or delay publication to protect any proprietary information.