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MRA With Feraheme in HHT

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ClinicalTrials.gov Identifier: NCT02977637
Recruitment Status : Completed
First Posted : November 30, 2016
Last Update Posted : January 25, 2019
Sponsor:
Information provided by (Responsible Party):
Justin McWilliams, MD, University of California, Los Angeles

Tracking Information
First Submitted Date  ICMJE November 28, 2016
First Posted Date  ICMJE November 30, 2016
Last Update Posted Date January 25, 2019
Study Start Date  ICMJE November 2016
Actual Primary Completion Date November 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 28, 2016)
Presence or absence of AVM [ Time Frame: Immediate ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02977637 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 28, 2016)
  • Size of AVM [ Time Frame: Immediate ]
  • Location of AVM [ Time Frame: Immediate ]
  • Overall image quality score [ Time Frame: Immediate ]
  • Artifact score [ Time Frame: Immediate ]
  • Vessel definition score [ Time Frame: Immediate ]
  • Number of AVM feeding arteries [ Time Frame: Immediate ]
  • Dimension of largest AVM feeding artery [ Time Frame: Immediate ]
  • Number of AVM draining veins [ Time Frame: Immediate ]
  • Dimension of largest AVM draining vein [ Time Frame: Immediate ]
  • Dimension of aneurysmal sac [ Time Frame: Immediate ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MRA With Feraheme in HHT
Official Title  ICMJE The Use of Ferumoxytol (Feraheme) for Whole Body Magnetic Resonance Angiography in Hereditary Hemorrhagic Telangiectasia
Brief Summary

Magnetic resonance (MR) imaging is performed with contrast agents to highlight the blood vessels and allow interpretation and diagnosis of blood vessel abnormalities. HHT (Hereditary Hemorrhagic Telangiectasia) is a disease of blood vessels, and can suffer fatal bleeding if abnormal blood vessels are not detected and treated early. Patients with HHT also require many imaging studies through their lifetimes for surveillance of blood vessels. Many HHT patients also have co-existing iron deficiency anemia from bleeding in their nose and gastrointestinal tract, and receive daily iron therapy.

Ferumoxytol is an alternative MR contrast agent, which is FDA (Food and Drug Administration) approved for the treatment of iron deficiency anemia. In addition, it is not associated with the risks to the kidneys of the other agents. The use of ferumoxytol for MR imaging may benefit the patients who do not currently receive imaging due to the contraindications of the conventional contrast agents. It avoids the use of ionizing radiation. Also, the conventional contrast agents are associated with risks. Iodinated contrast in CT is associated with significant risks of kidney damage. Another imaging technique, MR, uses gadolinium based contrast agents. Gadolinium, if used in patients with pre existing kidney dysfunction (defined as GFR < 30ml/min) is associated with the development of another devastating disease called nephrogenic systemic fibrosis. As HHT patients will require repeated scans throughout their lifetimes, this study will provide them a safer alternative.

Ten patients from the HHT clinic in whom the use of ferumoxytol as an MR agent is clinically indicated will be invited to participate in this study, which will determine if MR with ferumoxytol is able to detect and characterize vascular malformations in HHT.

Detailed Description

The safety of the use of gadolinium based contrast agents in MR is a concern for the FDA, with risks of development of nephrogenic systemic fibrosis and the more recent discovery of accumulation of gadolinium in the brain in patients who have received multiple prior MR scans.

Hereditary hemorrhagic telangiectasia (HHT) manifests with multiple vascular malformations (VMs) in the skin, mucous membranes and solid organs affecting the spine, brain, liver, gastrointestinal tract, pancreas, and lungs. The disease has an autosomal dominant inheritance and affects 1 in 5000 individuals.

Cerebral vascular malformations occur in 23 % of HHT patients, with a bleeding risk of 0.5% per year. Pulmonary AVMs occur in 15-50% of HHT patients, with a complication rate of 50% ranging from fatal hemoptysis or hemothorax to stroke or cerebral abscess. Liver vascular malformations are present in 32-78% of HHT patients.

The rationale for screening for vascular malformations is detection of a treatable lesion prior to the development of a fatal complication. The international guidelines currently recommend different first line screening tests in each organ: MRI for cerebral VMs, transthoracic echocardiography for pulmonary VMs, endoscopy for gastrointestinal VMs, Doppler US or CT for liver VMs.

Contrast enhanced magnetic resonance angiography (CE-MRA) may play an important role in the simultaneous whole body screening of vascular malformations. The advantages of CE-MRA include visualization of the entire body vasculature in one examination, high spatial resolution comparable to CT, no ionizing radiation and easy of multiplanar reconstructions.

Substituting a conventional gadolinium based contrast agent (GBCA) with an ultra small, super paramagnetic iron oxide agent (USPIO) e.g ferumoxytol, will eliminate any potential risk of developing nephrogenic systemic fibrosis. Since 2009, ferumoxytol ('Feraheme' Advanced Magnetics, Cambridge, MA) has been FDA approved for the treatment of iron deficiency anemia in adult patients with chronic kidney disease. The results of prior studies suggest that ferumoxytol is comparable to standard GBCAs for CE- MRA. Our experience with use of ferumoxytol to date suggests that it will be a superior agent for detection of vascular malformations in a range of vascular territories and that it will be uniquely capable of interrogating multiple territories in one sitting, due to its highly stable intravascular residence time.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Hereditary Hemorrhagic Telangiectasia
Intervention  ICMJE Procedure: Feraheme MRI/MRA
Other Name: Ferumoxytol
Study Arms  ICMJE Experimental: Feraheme group
All patients enrolled in the study will receive Feraheme MRI/MRA to detect vascular malformations. Ferumoxytol in its standard concentration (510 mg in 17 cc) will be administered IV at 0.15-0.21 mg/kg prior to MRI/MRA.
Intervention: Procedure: Feraheme MRI/MRA
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 28, 2016)
10
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2018
Actual Primary Completion Date November 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Definite diagnosis of HHT (clinically or genetically confirmed)
  • Known or suspected AVMs in the brain, lung, and/or liver
  • Use of ferumoxytol as an MR agent is clinically indicated

Exclusion Criteria:

  • Age <18
  • Unable to have MRI scan
  • Prior adverse reaction to ferumoxytol
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02977637
Other Study ID Numbers  ICMJE 15-001308
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Justin McWilliams, MD, University of California, Los Angeles
Study Sponsor  ICMJE University of California, Los Angeles
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Justin McWilliams, MD University of California, Los Angeles
PRS Account University of California, Los Angeles
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP