Phase II, Open Label, Randomized, Multicenter Trial Comparing Noncontrast MRA vs. Ferumoxytol Vascular Enhanced MRI for Detection of Stenosis or Occlusion of the Aortoiliac and Superficial Femoral Arteries in PAD Subjects Scheduled for DSA
Overview
- Phase
- Phase 2
- Intervention
- ferumoxytol
- Conditions
- Peripheral Arterial Disease (PAD)
- Sponsor
- AMAG Pharmaceuticals, Inc.
- Enrollment
- 119
- Locations
- 1
- Primary Endpoint
- To assess sensitivity and specificity of non-contrast MRA and VE-MRI at three ferumoxytol dosing levels
- Status
- Completed
- Last Updated
- 16 days ago
Overview
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."
Investigators
Eligibility Criteria
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
Arms & Interventions
Cohort 1
1.0 mg/kg IV ferumoxytol versus non-contrast MRA
Intervention: ferumoxytol
Cohort 2
2.5 mg/kg IV ferumoxytol versus non-contrast MRA
Intervention: ferumoxytol
Cohort 3
4.0 mg/kg IV ferumoxytol versus non-contrast MRA
Intervention: ferumoxytol
Outcomes
Primary Outcomes
To assess sensitivity and specificity of non-contrast MRA and VE-MRI at three ferumoxytol dosing levels
Time Frame: 3 weeks
Segment-level Sensitivity and Specificity of VE-MRI at 3 Ferumoxytol Dosing Levels and Differences in Sensitivity and Specificity by Dose Group
Time Frame: 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
Time Frame: 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 Outcomes
- To assess positive and negative predictive values of VE-MRI using ferumoxytol at different dosing levels.(3 weeks)
- Segment-level Positive and Negative Predictive Values of VE-MRI Using Ferumoxytol at 3 Dosing Levels(3 weeks)
- Segment-level Positive and Negative Predictive Values of Noncontrast MRA(3 weeks)
- Segment-level Total Percent, Positive Percent Between VE-MRI and Noncontrast MRA(3 weeks)
- Segment Level Sensitivity and Specificity of VE-MRI by Dosing Within Platforms and Independent Readers(3 weeks)
- Segment-level Negative Percent Agreements VE-MRI and Noncontrast MRA(3 weeks)
- Segment-level Total Percent, Kappa Statistics Between VE-MRI and Noncontrast MRA(3 weeks)