Magnetic Resonance Angiography for Peripheral Arterial Disease (PAD)

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

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).

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Disease (PAD)
• Intervention / Treatment: Drug: ferumoxytol; Drug: ferumoxytol; Drug: ferumoxytol

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."

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Lexington, Massachusetts, United States, 02421

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 1.0 mg/kg IV ferumoxytol versus non-contrast MRA	Drug: ferumoxytol; 1.0 mg/kg IV ferumoxytol; Drug: ferumoxytol; 2.5 mg/kg IV ferumoxytol; Drug: ferumoxytol; 4.0 mg/kg IV ferumoxytol
Experimental: Cohort 2; 2.5 mg/kg IV ferumoxytol versus non-contrast MRA	Drug: ferumoxytol; 1.0 mg/kg IV ferumoxytol; Drug: ferumoxytol; 2.5 mg/kg IV ferumoxytol; Drug: ferumoxytol; 4.0 mg/kg IV ferumoxytol
Experimental: Cohort 3; 4.0 mg/kg IV ferumoxytol versus non-contrast MRA	Drug: ferumoxytol; 1.0 mg/kg IV ferumoxytol; Drug: ferumoxytol; 2.5 mg/kg IV ferumoxytol; Drug: ferumoxytol; 4.0 mg/kg IV ferumoxytol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Segment-level Sensitivity and Specificity of VE-MRI at 3 Ferumoxytol Dosing Levels and Differences in Sensitivity and Specificity by Dose Group	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.	3 weeks
Segment-level Sensitivity and Specificity of Noncontrast MRA at 3 Ferumoxytol Dosing Levels and Difference From Sensitivity by Dose Group	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.	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Segment-level Positive and Negative Predictive Values of VE-MRI Using Ferumoxytol at 3 Dosing Levels	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.	3 weeks
Segment-level Positive and Negative Predictive Values of Noncontrast MRA	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.	3 weeks
Segment-level Total Percent, Positive Percent Between VE-MRI and Noncontrast MRA	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.	3 weeks
Segment Level Sensitivity and Specificity of VE-MRI by Dosing Within Platforms and Independent 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.	3 weeks
Segment-level Negative Percent Agreements VE-MRI and Noncontrast MRA	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.	3 weeks
Segment-level Total Percent, Kappa Statistics Between VE-MRI and Noncontrast MRA	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.	3 weeks

Collaborators and Investigators

• Sponsor: AMAG Pharmaceuticals, Inc.
• Investigators: Study Director: William Strauss, MD, AMAG Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2008
• Primary Completion (Actual): July 2, 2010
• Study Completion (Actual): August 15, 2020

Study Registration Dates

• First Submitted: June 27, 2008
• First Submitted That Met QC Criteria: June 30, 2008
• First Posted (Estimated): July 1, 2008

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Magnetic Resonance Imaging (MRI); Peripheral arterial disease (PAD); Magnetic Resonance Angiography (MRA); imaging agent or biomarker
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Peripheral Arterial Disease; Inorganic Chemicals; Ferric Compounds; Iron Compounds; Ferrous Compounds; Minerals; Ferrosoferric Oxide
• Other Study ID Numbers: FER-PAD-001