Clinical trial NCT02954510: Ferumoxytol-enhanced Magnetic Resonance Imaging
Official title: Ferumoxytol-enhanced Magnetic Resonance Imaging for the Interpretation of Vascular Defects
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Coronary Artery Disease
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2016-11-03
Enrollment: 185
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: case control
Primary purpose: DIAGNOSTIC

Brief summary: There are no current alternatives to diagnostic contrast-requiring imaging for patients with an eGFR \<30mL/min due to the association of gadolinium-based imaging modalities to nephrogenic systemic fibrosis and iodinated contrast-induced kidney injury. Ferumoxytol-enhanced imaging may offer an alternative approach.

Detailed description: This is a case control study which will assess the resolution by which the coronary arteries can be visualized using ferumoxytol-enhanced cardiac magnetic resonance angiography (fcMRA) in patients with prior regional cardiac ischemia localized by stress-induced echocardiography. Resolution will be compared to invasive coronary arteriography completed in all patients that will be analyzed at the end of the study.

Masked experts will interpret fcMRA images to determine if coronary stenosis is present or absent. By strict definitions, this is a single-arm study. However comparison will be made between fcMRA and invasive coronary arteriography performed in each patient. With a prevalence of disease of approximately 0.35 in the study population, it is anticipated that both sensitivity and specificity of fcMRA to identify the absence of coronary artery stenosis can be calculated.

We anticipate a population size of 70 will be needed to adequately study the primary outcome due to potential confounders, including racial and sex differences which may exist (see below), which are known to exist in a population with significant renal and possible cardiac disease to determine if fcMRA is differs in its ability to exclude greater than or equal to 50 percent stenosis in a single coronary artery compared to dobutamine stress echocardiography (DSE). This is based on prevalence of disease of 0.35. Non-invasive cardiac stress testing in those with eGFR \<30ml/min/1.73m2 is estimated to have a sensitivity of 0.81 (CI 0.57-0.94) and specificity of 0.83 (CI 0.62-0.95) to identify coronary epicardial lesion of greater than 70 percent. The sensitivity of non-invasive non-intraluminal testing is anticipated to be 0.60 when patients with myocardial scar are enrolled. We anticipate that 50 percent of patients with a positive DSE will have evidence of myocardial scar. Predicted sensitivity of fcMRA will likely be increased compared to referenced estimates because true positives will be defined by stenosis greater than or equal to 50 percent. Based on a prevalence of 0.35, we anticipate DSE will yield 24 true positives, 25 true negatives, 7 false positives, and 14 false negatives resulting in sensitivity of 0.63 and specificity of 0.78. To achieve study power that will allow for the null hypothesis to be ignored, in as study size of 70, fcMRA must yield at least 28 true positives and 27 true negatives allowing for 5 false positives and 10 false negatives resulting in sensitivity of 0.737 and specificity of 0.843. To account for drop-out and incomplete data collection in 50 percent of patients approached, recruitment of 140 patients will be needed. The drop-out rate from recruitment to enrollment approximates the fcMRA study experience at the Brigham and Women's Hosptial in 2017.

Racial/sex subgroup analysis will involve testing in whites vs. non-whites and males vs. females. Prevalence of 0.35 will again be assumed. Previously, 45 percent of patients enrolled were of non-white racial origin. An additional 85 patients would be necessary to demonstrate a difference between fcMRA and DSE when comparing sensitivity and specificity as above, therefore this will be considered an exploratory analysis.

Using the Partners Healthcare System Research Patient Data Registry (RPDR) all patients in calendar year 2017 were identified with a diagnosis of chronic kidney disease stage 4-5D and who underwent a left heart cardiac catheterization at either Brigham and Women's Hospital or Massachusetts General Hospital (MGH). "chronic kidney disease stage 4", "chronic kidney disease stage 5", and "left heart catheterization", and "abnormal echocardiogram" were used as mesh terms resulting in 68 patients. 108 patients utilizing hemodialysis or peritoneal dialysis completed ICA. 35 patients not yet requiring renal replacement therapy completed ICA in the same time period. Separately, clinical practices at the Brigham and Women's Hospital kidney transplant center in calendar year 2017 were reviewed. 207 patients underwent non-invasive cardiac stress testing and 16 patients underwent ICA. All patients that underwent arteriography had prior non--invasive cardiac stress testing. Surveying both the inpatient and outpatient settings a total of 159 patients were identified in the Partners Healthcare System that would have qualified for the proposed study.

Eligibility criteria: Both female and male participants are being studied aged 18-85 years old with an estimated glomerular filtration rate (eGFR) of less than 30ml/min/1.73 meters squared. Patients will have undergone cardiac screening tests that warrant further evaluation. Patients will be excluded with an eGFR \>30ml/min/1.73 meters squared.

Primary outcomes:
measure: Detect the absence of ≥50% stenosis in the coronary artery tree
timeFrame: 48 months
Secondary outcomes:
measure: Detect stenosis in proximal and distal segments of the coronary artery tree
timeFrame: 48 months
measure: Compare ferumoxtyol enhanced magnetic resonance angiography with stress echocardiography
timeFrame: 48 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
References:
citation: Chin MS, Steigner M, Yin W, Kwong RY, Siedlecki AM. Intraluminal Assessment of Coronary Arteries With Ferumoxytol-Enhanced Magnetic Resonance Angiography. JACC Cardiovasc Imaging. 2018 Mar;11(3):505-508. doi: 10.1016/j.jcmg.2017.10.017. Epub 2017 Dec 13. No abstract available.