Heart Failure, Congestive
Conditions
Keywords
Heart Failure, nuclear cardiology, sympathetic innervation, 123I-mIBG
Brief summary
The study is designed to study the utility of 123I-mIBG as a diagnostic imaging agent to predict cardiac outcomes in subjects with heart failure and in comparison to subjects without cardiovascular disease.
Interventions
Single dose
Sponsors
GE Healthcare
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Study subjects must be adults with an established diagnosis of heart failure (New York Heart Association Class II or III) and reduced left ventricular ejection fraction (LVEF) (≤ 35%) or be healthy volunteers without heart disease.
Exclusion criteria
* Healthy volunteers are not eligible if they have a history diabetes mellitus, signs/symptoms of neurological disease (eg, Parkinson's Disease, multiple system atrophy, Parkinsonian syndromes), or other diseases known to affect the sympathetic nervous system. * Subjects with New York Heart Association Class I or IV heart failure are not eligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relationship Between the Occurrence of Adverse Cardiac Event and 123I-mIBG Uptake on Planar Scintigraphy Categorized as High or Low Heart to Mediastinum (H/M) Ratio | Approximately 24 months from the date of administration of 123I-mIBG | H/M ratio for 123I-mIBG uptake at 3 hours 50 minutes post administration was calculated by dividing the counts/pixel in the total myocardium region of interest (ROI) by the counts/pixel in the 7x7 pixel mediastinal ROI. Assessments were done by 3 independent readers. H/M ratios were categorized as 'Low' and 'High' based on being \<1.6 or ≥1.6 respectively. The efficacy of 123I-mIBG was based on the prognostic value of the imaging data collected relative to time to adverse cardiac events. |
Countries
United States
Participant flow
Recruitment details
A total of 712 participants were screened, of whom 587 participants were enrolled.
Pre-assignment details
Of 587 participants, 6 were withdrawn prior to receiving investigational medicinal product (IMP). A total of 581 participants (533 Heart Failure \[HF\] and 48 control), were dosed at the 54 centers. However, one of these participants was administered 123I-mIBG not manufactured by the sponsor, and therefore excluded from all analyses.
Participants by arm
| Arm | Count |
|---|---|
| AdreView--Heart Failure Group 123I-mIBG (meta-iodobenzylguanidine): 10 mCi as a single intravenous dose, to participants who were at a high risk of heart failure. | 532 |
| AdreView--Control Group 123I-mIBG (meta-iodobenzylguanidine): 10 mCi as a single intravenous dose, to participants who were at no risk of heart failure. | 48 |
| Total | 580 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Failed Inclusion Exclusion Criteria | 1 | 0 |
| Overall Study | Lost to Follow-up | 8 | 4 |
| Overall Study | Other | 5 | 0 |
| Overall Study | Protocol Violation | 9 | 6 |
| Overall Study | Withdrawal by Subject | 17 | 1 |
Baseline characteristics
| Characteristic | AdreView--Heart Failure Group | AdreView--Control Group | Total |
|---|---|---|---|
| Age, Continuous | 63.0 years STANDARD_DEVIATION 11.33 | 56.4 years STANDARD_DEVIATION 11.97 | 61.3 years STANDARD_DEVIATION 11.37 |
| Sex: Female, Male Female | 92 Participants | 20 Participants | 112 Participants |
| Sex: Female, Male Male | 440 Participants | 28 Participants | 468 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 532 | 0 / 48 |
| serious Total, serious adverse events | 1 / 532 | 0 / 48 |
Outcome results
Primary
Relationship Between the Occurrence of Adverse Cardiac Event and 123I-mIBG Uptake on Planar Scintigraphy Categorized as High or Low Heart to Mediastinum (H/M) Ratio
H/M ratio for 123I-mIBG uptake at 3 hours 50 minutes post administration was calculated by dividing the counts/pixel in the total myocardium region of interest (ROI) by the counts/pixel in the 7x7 pixel mediastinal ROI. Assessments were done by 3 independent readers. H/M ratios were categorized as 'Low' and 'High' based on being \<1.6 or ≥1.6 respectively. The efficacy of 123I-mIBG was based on the prognostic value of the imaging data collected relative to time to adverse cardiac events.
Time frame: Approximately 24 months from the date of administration of 123I-mIBG
Population: Primary efficacy population was 520 participants in HF group who received IMP and had a diagnostic (optimal or sub-optimal) 3 hour 50 minute planar image. Images from 2 HF participants were inadvertently not submitted and not presented to blinded readers. Here, N=efficacy population and n=number of participants assessed by specific readers.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AdreView-Heart Failure Group With High H/M Ratio | Relationship Between the Occurrence of Adverse Cardiac Event and 123I-mIBG Uptake on Planar Scintigraphy Categorized as High or Low Heart to Mediastinum (H/M) Ratio | Reader A (n=115, 401) | 14 number of adverse cardiac events |
| AdreView-Heart Failure Group With High H/M Ratio | Relationship Between the Occurrence of Adverse Cardiac Event and 123I-mIBG Uptake on Planar Scintigraphy Categorized as High or Low Heart to Mediastinum (H/M) Ratio | Reader B (n=115, 403) | 14 number of adverse cardiac events |
| AdreView-Heart Failure Group With High H/M Ratio | Relationship Between the Occurrence of Adverse Cardiac Event and 123I-mIBG Uptake on Planar Scintigraphy Categorized as High or Low Heart to Mediastinum (H/M) Ratio | Reader C (n=116, 402) | 14 number of adverse cardiac events |
| AdreView-Heart Failure Group With Low H/M Ratio | Relationship Between the Occurrence of Adverse Cardiac Event and 123I-mIBG Uptake on Planar Scintigraphy Categorized as High or Low Heart to Mediastinum (H/M) Ratio | Reader A (n=115, 401) | 100 number of adverse cardiac events |
| AdreView-Heart Failure Group With Low H/M Ratio | Relationship Between the Occurrence of Adverse Cardiac Event and 123I-mIBG Uptake on Planar Scintigraphy Categorized as High or Low Heart to Mediastinum (H/M) Ratio | Reader B (n=115, 403) | 100 number of adverse cardiac events |
| AdreView-Heart Failure Group With Low H/M Ratio | Relationship Between the Occurrence of Adverse Cardiac Event and 123I-mIBG Uptake on Planar Scintigraphy Categorized as High or Low Heart to Mediastinum (H/M) Ratio | Reader C (n=116, 402) | 100 number of adverse cardiac events |
Comparison: Analysis based on Reader A readings. Data analysis to assess the relative hazard of an adverse cardiac event was performed using a Cox proportional hazards model. Hazard (risk) of an event for a participant with low H/M at time t was expressed as Hl (t)/ Hh (t) = Ψ, where Hl (t) and Hh (t) denote the hazard of an event at time t for participants with low H/M and high H/M respectively.p-value: =0.00495% CI: [0.23, 0.83]Cox Proportional Hazards Model
Comparison: Analysis based on Reader B readings. Data analysis to assess the relative hazard of an adverse cardiac event was performed using a Cox proportional hazards model. Hazard (risk) of an event for a participant with low H/M at time t was expressed as Hl (t)/ Hh (t) = Ψ, where Hl (t) and Hh (t) denote the hazard of an event at time t for participants with low H/M and high H/M respectively.p-value: =0.00495% CI: [0.23, 0.84]Cox Proportional Hazards Model
Comparison: Analysis based on Reader C readings. Data analysis to assess the relative hazard of an adverse cardiac event was performed using a Cox proportional hazards model. Hazard (risk) of an event for a participant with low H/M at time t was expressed as Hl (t)/ Hh (t) = Ψ, where Hl (t) and Hh (t) denote the hazard of an event at time t for participants with low H/M and high H/M respectively.p-value: =0.00495% CI: [0.23, 0.84]Cox Proportional Hazards Model