Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02146768 |
| Other study ID # |
013-234 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
March 3, 2014 |
| Last updated |
June 9, 2017 |
| Start date |
January 2014 |
Study information
| Verified date |
June 2017 |
| Source |
Baylor Research Institute |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Low-dose-contrast CCTA can effectively and safely assess the aortic valve apparatus, and
effectively direct the trans-catheter heart valve (THV) size selection by providing accurate
annulus sizing, and provide adequate pre-procedural risk-stratification guidance for
TAVR/TAVI.
Description:
A. INTENT AND PURPOSE
Background:
Optimizing procedural and patient outcomes relies heavily on tomographic imaging data
guidance for patients being evaluated for trans-catheter aortic valve replacement or
implantation (TAVR) by providing accurate information of the aortic valve apparatus (aortic
annulus and its pertinent neighboring structures).
The aortic valve annulus is a dynamic complex elliptical or ovoid 3D entity that is also
subject to constant shape deformation across the cardiac cycle in addition to being
influenced by the thoracic and intra-thoracic anatomy or variations. Given this inherent
nature of the aortic valve annulus, electrocardiographic gated cardiac computed tomographic
angiography (CCTA), a robust dynamic 3-dimensional imaging modality, is now widely accepted
as the "gold-standard" for evaluating the aortic valve apparatus (AVA). To maximize the
information obtained by CT, imaging needs to be performed with intravenous contrast
injection.2 CCTA requires administration of iodinated contrast. The volume of iodinated
contrast medium is of concern in many patients because candidates for TAVR frequently have
impaired renal function.2 Contrast reduction and adherence to protocols for prevention of
contrast-induced nephropathy is recommended.2 For access planning via the ilio-femoral
route, some groups have reported direct aortic injection with extremely low volumes of
contrast.
Reduction of contrast volumes for CCTA of the AVA can be achieved by using lower flow rates
than for coronary CT angiography. Although 5 mL/s is typically recommended for coronary
imaging, 3 mL/s may sometimes be sufficient for imaging patients in the workup for TAVR.2
Though suggested, these CCTA lower flow rates have not been systematically performed and
validated in a population being evaluated for candidacy for TAVR. And as recommended by
guidelines, a standard bolus of 80 mL to 120 mL of low-osmolar iodinated contrast is usually
necessary for optimal TAVR CCTA scanning.1 In these patients, reducing the dose of iodinated
contrast at the time of CCTA acquisition in an attempt to minimize renal injury, and at the
same time being able to accurately assess the aortic annulus apparatus (AVA) will be of
paramount importance. Some reduction of contrast nephropathy can be accomplished by
minimizing contrast volume and the use of iso-osmolar or low-osmolar contrast agents. It has
been suggested that the contrast volume threshold can be estimated by using the ratio of
contrast volume to creatinine clearance. Nephrotoxicity is more likely when the contrast
volume/creatinine clearance ratio exceeds 3.7:1.12 And using this, 3.7 x eGFR (estimated
glomerular filtration rate) can be set as the maximal contrast dose for an imaging test or
invasive procedure.12 14 CCTA acquisition methods Images were acquired with a Brilliance
64-slice CT scanner (Philips Healthcare, Andover, Massachusetts, USA). As per the
recommendations on radiation protection in cardiovascular CT by the Society of
Cardiovascular Computed Tomography (SCCT), a tube potential of 100 kV will be considered for
patients weighing <90 kg or with a body mass index (BMI) <30; whereas a tube potential of
120 kV will be considered for patients weighing >90 kg and with a BMI >30. It will be
adjusted, based on each individual patient's size, to the lowest setting that guarantees
acceptable image noise for a suitable signal-to-noise ratio (SNR) to perform analysis.15 The
patients' eGFR was first calculated using the MDRD (modification of disease in renal diet)
GFR formula. The maximal allowable contrast dose for the CCTA was calculated using 3.7 x
[(patient's BSA/1.73) x MDRD-eGFR].14 Next, the dose of contrast chosen for the CCTA was <
50% of the maximal allowable contrast dose. The MDRD formula can underestimate the GFR by
about 6.2% in patients with chronic kidney disease and by about 29% in healthy individuals,
making this an extremely suitable conservative approach for calculating the contrast dosing,
with a tendency only to underdose and never to overdose the contrast. With our extensive
experience in doing this, we have decreased the total contrast dose for CCTA of the AVA to
45 ml with satisfactory image quality and SNR for post-processing.
Two separate acquisitions (ECG-synchronized for the aortic root and non-gated for the aorta
and peripheral vessels) may be preferable to an ECG-synchronized acquisition of the entire
volume to reduce the amount of contrast agent.2 A total contrast dose of 45 ml is essential
for ECG-synchronized CCTA that utilizes a 64-multislice CT scanner (MSCT) in order to obtain
satisfactory image quality and SNR of the aortic root. Depending on the remaining amount of
allowable contrast, a decision was then made to perform a non-gated CT of the aorta and
peripheral vessels either with no contrast or a low-dose-contrast protocol that we have in
place for selectively enhancing the ilio-femoral arterial regions.
The DICOM data will be post-processed by a workstation capable of advanced image processing,
manipulation and optimal multi-planar reformatting.
B. CLINICAL HYPOTHESIS AND OBJECTIVES
Hypothesis:
Low-dose-contrast CCTA can effectively and safely assess the aortic valve apparatus, and
effectively direct the trans-catheter heart valve (THV) size selection by providing accurate
annulus sizing, and provide adequate pre-procedural risk-stratification guidance for
TAVR/TAVI.
Study Design:
The proposed investigation is a retrospective cross-sectional study assessing image quality
and safety from a renal standpoint between low-dose-contrast CCTA and
traditional-dose-contrast, and effectiveness of low-dose-contrast CCTA in analyzing the
complex dynamic 3-pronged aortic annulus geometry pre-procedurally in TAVR to improve
procedural and patient outcomes. The study cohort will comprise 150 consecutive patients (75
patients who received low-dose contrast matched by body mass index with 75 patients who
received traditional dose contrast) seen at THHBP between January 1, 2011 and June 30, 2013.
Statistical Analysis:
The Bland and Altman plot ratios method comparison will be utilized and the graphs
displaying a scatter diagram of the ratios plotted against the averages of the SNR of
ascending aorta (SNR-AA) obtained with the two different acquisitions (comparing image
quality) will be generated. A generalized propensity score (to adjust for pre-operative
clinical and non-clinical factors) approach accounting for the matching will be used to
account for possible confounding of the association between low and traditional dose groups
and annulus area, annulus perimeter, and maximum and minimum annulus diameter measurements.
Moreover, adjusted (by the propensity score) Kappa tests, specificity, and sensitivity will
be used to assess agreement between low and traditional dose groups. The outcomes are: CT
guided successful TAVR deployment; unsuccessful TAVR deployment (moderate-severe
paravalvular leak, rupture, valve embolization, mortality); acute renal failure will be
defined as a reduction (pre vs post procedure) in renal function as defined by the RIFLE
criteria, occurring will be used to assess differences between the study groups.
Sample Size Considerations:
A study cohort of 50 patients enables the detection of a minimum absolute difference of 3%
in the primary outcome incidence (power>80) assuming α=0.05, two-sided test.
B1. Personnel Principal Investigator - Ambarish Gopal Sub-Investigators - Deepika Gopal,
Paul Grayburn, William Brinkman, David Brown Research coordinators - Molly Mack, Cecile
Mahoney, Christine McKibben, Christina Worley, Jessica Jones Epidemiologist - Giovanni
Filardo, PhD, MPH Proposal and Protocol Development-Natalie Settele, PA-C B2. Patients will
require the following tests/Lab equipment Patients will have received ECG-gated CTA on a 64
slice CT scanner as standard of care treatment B3. Patient Population The study is a
retrospective study of 150 consecutive patients > 18 years of age (75 patients who received
low-dose contrast matched by body mass index with 75 patients who received traditional dose
contrast) seen at THHBP between January 1, 2011 and June 30, 2013. Patients with MDRD eGFR <
25 will be excluded. The cutoff of 25 was chosen as the maximal allowable dose of contrast
for eGFR of 25 would be about 90 ml (3.7 x eGFR of 25), and half of that maximal allowable
contrast would be 45 ml (the minimum we require to obtain a CCTA with acceptable SNR for
post-processing).
B4. Risks There are no risks to subjects as this is a retrospective trial.
