Meta-Iodobenzylguanidine Scintigraphy Imaging in Patients With Heart Failure and Control Subjects Without Cardiovascular Disease
Sponsor
GE Healthcare (Industry)
Overall Status
Completed
CT.gov ID
NCT00126425
Collaborator
(none)
587
1
1
41
14.3
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
587 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Diagnostic
Official Title:
An Open-Label, Multicenter, Phase 3 Study Evaluating the Prognostic Usefulness of I-123 mIBG Scintigraphy for Identifying Subjects With Heart Failure Who Will Experience an Adverse Cardiac Event
Study Start Date
:
Jul 1, 2005
Actual Primary Completion Date
:
Jul 1, 2008
Actual Study Completion Date
:
Dec 1, 2008
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 123I-mIBG (meta-iodobenzylquanidine Single dose |
Drug: 123I-mIBG (meta-iodobenzylguanidine)
Single dose
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GE Healthcare | Princeton | New Jersey | United States | 08540 |
Sponsors and Collaborators
- GE Healthcare
Investigators
- Study Director: John Lombard, GE Healthcare
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
GE Healthcare
ClinicalTrials.gov Identifier:
NCT00126425
Other Study ID Numbers:
- MBG311
First Posted:
Aug 4, 2005
Last Update Posted:
Dec 13, 2016
Last Verified:
Oct 1, 2016
Keywords provided by GE Healthcare
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | A total of 712 participants were screened, of whom 587 participants were enrolled. |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | AdreView--Heart Failure Group | AdreView--Control Group |
|---|---|---|
| Arm/Group Description | 123I-mIBG (meta-iodobenzylguanidine): 10 mCi as a single intravenous dose. | 123I-mIBG (meta-iodobenzylguanidine): 10 mCi as a single intravenous dose. |
| Period Title: Overall Study | ||
| STARTED | 539 | 48 |
| COMPLETED | 498 | 37 |
| NOT COMPLETED | 41 | 11 |
Baseline Characteristics
| Arm/Group Title | AdreView--Heart Failure Group | AdreView--Control Group | Total |
|---|---|---|---|
| Arm/Group Description | 123I-mIBG (meta-iodobenzylguanidine): 10 mCi as a single intravenous dose, to participants who were at a high risk of heart failure. | 123I-mIBG (meta-iodobenzylguanidine): 10 mCi as a single intravenous dose, to participants who were at no risk of heart failure. | Total of all reporting groups |
| Overall Participants | 532 | 48 | 580 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
63.0
(11.33)
|
56.4
(11.97)
|
61.3
(11.37)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
92
17.3%
|
20
41.7%
|
112
19.3%
|
| Male |
440
82.7%
|
28
58.3%
|
468
80.7%
|
Outcome Measures
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | AdreView-Heart Failure Group With High H/M Ratio | AdreView-Heart Failure Group With Low H/M Ratio |
|---|---|---|
| Arm/Group Description | Participants in HF group who had high H/M ratio (more than or equal to 1.6) | Participants in HF group who had low H/M ratio (less than 1.6) |
| Measure Participants | 116 | 403 |
| Reader A (n=115, 401) |
14
|
100
|
| Reader B (n=115, 403) |
14
|
100
|
| Reader C (n=116, 402) |
14
|
100
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | AdreView-Heart Failure Group With High H/M Ratio, AdreView-Heart Failure Group With Low H/M Ratio |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.004 |
| Comments | At 0.025 level of significance. | |
| Method | Cox Proportional Hazards Model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.44 | |
| Confidence Interval |
(2-Sided) 95% 0.23 to 0.83 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | AdreView-Heart Failure Group With High H/M Ratio, AdreView-Heart Failure Group With Low H/M Ratio |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.004 |
| Comments | At 0.025 level of significance. | |
| Method | Cox Proportional Hazards Model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.44 | |
| Confidence Interval |
(2-Sided) 95% 0.23 to 0.84 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | AdreView-Heart Failure Group With High H/M Ratio, AdreView-Heart Failure Group With Low H/M Ratio |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.004 |
| Comments | At 0.025 level of significance. | |
| Method | Cox Proportional Hazards Model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.44 | |
| Confidence Interval |
(2-Sided) 95% 0.23 to 0.84 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Up to 30 hours after administration of the IMP | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | A total of 7 participants were withdrawn from the study, of which 6 were withdrawn prior to receiving IMP and 1 patient received 123I-mIBG of another manufacturer. Therefore, this latter participant was withdrawn from all analyses. | |||
| Arm/Group Title | AdreView--Heart Failure Group | AdreView --Control Group | ||
| Arm/Group Description | 123I-mIBG (meta-iodobenzylguanidine): 10 mCi as a single intravenous dose. | 123I-mIBG (meta-iodobenzylguanidine): 10 mCi as a single intravenous dose. | ||
All Cause Mortality |
||||
| AdreView--Heart Failure Group | AdreView --Control Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| AdreView--Heart Failure Group | AdreView --Control Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/532 (0.2%) | 0/48 (0%) | ||
| Cardiac disorders | ||||
| Death | 1/532 (0.2%) | 1 | 0/48 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| AdreView--Heart Failure Group | AdreView --Control Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/532 (0%) | 0/48 (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.
Results Point of Contact
| Name/Title | Jose M Zubeldia, M.D. |
|---|---|
| Organization | GE Healthcare |
| Phone | 011-44-1494-543137 |
| jose.zubeldia@ge.com |
Responsible Party:
GE Healthcare
ClinicalTrials.gov Identifier:
NCT00126425
Other Study ID Numbers:
- MBG311
First Posted:
Aug 4, 2005
Last Update Posted:
Dec 13, 2016
Last Verified:
Oct 1, 2016