Peripheral Arterial Disease (PAD)
Conditions
Keywords
Peripheral arterial disease (PAD), Magnetic Resonance Angiography (MRA), Magnetic Resonance Imaging (MRI), imaging agent or biomarker
Brief summary
The purpose of this study is to compare the difference between two magnetic resonance imaging (MRI) techniques for visualizing arteries. The study hypothesizes that one method that relies upon imaging flowing blood in the pelvic and leg arteries will not be as accurate or efficient as injecting a safe imaging agent to change the appearance of the blood on the MRI. Both methods will be compared with Digital Subtraction Angiography (DSA).
Detailed description
This was a Phase 2, open-label, randomized, multicenter study to evaluate the efficacy and safety of a single administration of intravenous (IV) ferumoxytol at 3 dose levels as a VE-MRI imaging agent to facilitate detection of arterial stenosis in subjects with PAD. Eligible subjects were already scheduled for DSA to be completed within 14 days of the MR assessments. Nineteen sites randomized subjects in the study. The sites were selected such that an equal number of subjects could be scanned on the 3 major MRI 1.5 T platforms (Siemens, General Electric, and Philips). Subjects were stratified by imaging platform and randomized to receive 1.0, 2.5, or 4.0 mg/kg IV ferumoxytol. On the same study day, subjects first underwent a noncontrast MRA, followed by administration of the randomized ferumoxytol dose and VE-MRI. Within 2 weeks subjects then underwent the previously scheduled DSA of the aortoiliac and superficial femoral arteries that served as the reference "gold standard."
Interventions
DRUGferumoxytol
1.0 mg/kg IV ferumoxytol
Sponsors
AMAG Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with symptoms of PAD * Scheduled for DSA
Exclusion criteria
* Critical leg ischemia manifested by ulcers, gangrene or leg amputation * Laboratory evidence of iron overload, liver disease, pregnancy * History of allergy to or recent exposure to radiocontrast, gadolinium chelates, or intravenous iron therapy * Clinical concerns about co-morbidities, subject suitability
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Segment-level Sensitivity and Specificity of VE-MRI at 3 Ferumoxytol Dosing Levels and Differences in Sensitivity and Specificity by Dose Group | 3 weeks | Analysis of the sensitivity and specificity of VE-MRI by dose group was performed on the ITD segments by 3 Readers. The per reader comparison of VE-MRI sensitivity and noncontrast MRA sensitivity will take into account that readings are correlated because each subject (and segments) undergo both VE-MRI and noncontrast MRA scans. The differences between ferumoxytol dose groups for the difference between VE-MRI and noncontrast MRA will be reported. The data were pooled across all imaging platforms. |
| Segment-level Sensitivity and Specificity of Noncontrast MRA at 3 Ferumoxytol Dosing Levels and Difference From Sensitivity by Dose Group | 3 weeks | Analysis of the sensitivity and specificity of noncontrast MRA by dose group was performed on the ITD segments by 3 Readers. The per reader comparison of VE-MRI sensitivity and noncontrast MRA sensitivity will take into account that readings are correlated because each subject (and segments) undergo both VE-MRI and noncontrast MRA scans. The differences between ferumoxytol dose groups for the difference between VE-MRI and noncontrast MRA will be reported. The data were pooled across all imaging platforms. The data were pooled across all imaging platforms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Segment-level Positive and Negative Predictive Values of VE-MRI Using Ferumoxytol at 3 Dosing Levels | 3 weeks | The sensitivity and specificity estimated by imaging platforms and dose group by imaging platforms will be reported and statistical tests of whether sensitivity/specificity differs by imaging platforms will be done. The per reader comparison of VE-MRI sensitivity and noncontrast MRA sensitivity will take into account that readings are correlated because each subject (and segments) undergo both VE-MRI and noncontrast MRA scans. The differences between ferumoxytol dose groups for the difference between VE-MRI and noncontrast MRA will be reported. The data were pooled across all imaging platforms. |
| Segment-level Positive and Negative Predictive Values of Noncontrast MRA | 3 weeks | The sensitivity and specificity estimated by imaging platforms and dose group by imaging platforms will be reported and statistical tests of whether sensitivity/specificity differs by imaging platforms will be done. The per reader comparison of VE-MRI sensitivity and noncontrast MRA sensitivity will take into account that readings are correlated because each subject (and segments) undergo both VE-MRI and noncontrast MRA scans. The differences between ferumoxytol dose groups for the difference between VE-MRI and noncontrast MRA will be reported. The data were pooled across all imaging platforms. |
| Segment-level Total Percent, Positive Percent Between VE-MRI and Noncontrast MRA | 3 weeks | The per reader comparison of VE-MRI sensitivity and noncontrast MRA sensitivity will take into account that readings are correlated because each subject (and segments) undergo both VE-MRI and noncontrast MRA scans. The differences between ferumoxytol dose groups for the difference between VE-MRI and noncontrast MRA will be reported. The data were pooled across all imaging platforms. |
| Segment Level Sensitivity and Specificity of VE-MRI by Dosing Within Platforms and Independent Readers | 3 weeks | The per reader comparison of VE-MRI sensitivity and noncontrast MRA sensitivity will take into account that readings are correlated because each subject (and segments) undergo both VE-MRI and noncontrast MRA scans. The differences between ferumoxytol dose groups for the difference between VE-MRI and noncontrast MRA will be reported. The data were pooled across all imaging platforms. |
| Segment-level Negative Percent Agreements VE-MRI and Noncontrast MRA | 3 weeks | The per reader comparison of VE-MRI sensitivity and noncontrast MRA sensitivity will take into account that readings are correlated because each subject (and segments) undergo both VE-MRI and noncontrast MRA scans. The differences between ferumoxytol dose groups for the difference between VE-MRI and noncontrast MRA will be reported. The data were pooled across all imaging platforms. |
| Segment-level Total Percent, Kappa Statistics Between VE-MRI and Noncontrast MRA | 3 weeks | The per reader comparison of VE-MRI sensitivity and noncontrast MRA sensitivity will take into account that readings are correlated because each subject (and segments) undergo both VE-MRI and noncontrast MRA scans. The differences between ferumoxytol dose groups for the difference between VE-MRI and noncontrast MRA will be reported. The data were pooled across all imaging platforms. |
Countries
United States
Contacts
STUDY_DIRECTORWilliam Strauss, MD
AMAG Pharmaceuticals, Inc.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 67 Participants |
| Age, Categorical Between 18 and 65 years | 52 Participants |
| Age, Continuous | 65.1 years STANDARD_DEVIATION 10.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 99 Participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 39 | 0 / 40 |
| other Total, other adverse events | 2 / 40 | 0 / 39 | 0 / 40 |
| serious Total, serious adverse events | 5 / 40 | 2 / 39 | 4 / 40 |
Outcome results
None listed