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 outcome 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 were not eligible if they had a history of diabetes mellitus, signs/symptoms of neurological disease (e.g., 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 were not eligible. * Subjects were excluded if they had previously received 123I-mIBG or 131I-mIBG or participated in a clinical study involving investigational medicinal product or devices within 30 days. * Subjects that had a pacemaker or had received defibrillation, anti-tachycardia pacing or cardioversion to treat a previous arrhythmic event or had an ICD inserted within 30 days before study entry 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. Data analysis to assess the relative hazard of an adverse cardiac event was performed only on HF participants categorized into 2 groups with H/M \<1.6 and H/M ≥1.6 using a Cox proportional hazards model. |
Countries
United States
Participant flow
Recruitment details
A total of 753 participants were screened, of whom 197 were screen failures due to inclusion/exclusion criteria; 24 withdrawn at participant's request; 2 withdrawn at investigator's request and 15 failed to complete all screening procedures.
Pre-assignment details
A total 515 participants (453 Heart failure \[HF\] and 62 control) were enrolled in the study and received a single dose of investigational medicinal product (IMP) at 43 investigational centers.
Participants by arm
| Arm | Count |
|---|---|
| AdreView - Heart Failure AdreView (123I-mIBG): 10 mCi as a single intravenous dose. | 453 |
| Adreview - Control Group AdreView (123I-mIBG): 10 mCi as a single intravenous dose. | 62 |
| Total | 515 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 22 | 0 |
| Overall Study | Protocol Violation | 8 | 8 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
| Overall Study | Withdrawal due to adverse event | 1 | 0 |
Baseline characteristics
| Characteristic | AdreView - Heart Failure | Adreview - Control Group | Total |
|---|---|---|---|
| Age, Continuous | 61.5 years STANDARD_DEVIATION 12.38 | 58.8 years STANDARD_DEVIATION 10.84 | 61.2 years STANDARD_DEVIATION 12.2 |
| Sex: Female, Male Female | 102 Participants | 19 Participants | 121 Participants |
| Sex: Female, Male Male | 351 Participants | 43 Participants | 394 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 453 | 0 / 62 |
| serious Total, serious adverse events | 6 / 453 | 0 / 62 |
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. Data analysis to assess the relative hazard of an adverse cardiac event was performed only on HF participants categorized into 2 groups with H/M \<1.6 and H/M ≥1.6 using a Cox proportional hazards model.
Time frame: Approximately 24 months from the date of administration of 123I-mIBG
Population: Primary efficacy population included 444 participants in HF group who received IMP and had a diagnostic (optimal/sub-optimal) 3 hour 50 minute planar image. Primary efficacy analysis was based on comparing only Adreview HF participants with low vs. high H/M and, therefore, did not include Adreview Control group.
| 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=86, 355) | 11 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=86, 358) | 11 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=86, 352) | 11 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=86, 355) | 111 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=86, 358) | 113 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=86, 352) | 112 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: 0.00195% CI: [0.18, 0.73]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: 0.00195% CI: [0.18, 0.72]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: 0.00195% CI: [0.17, 0.72]Cox Proportional Hazards Model