Reduce Radiation Exposure in Fluoroscopic Interventions Evaluation (REDEFINE): A Prospective, Randomized Evaluation of the ControlRad System to Reduce Radiation Exposure During Cardiac Catheterization and Electrophysiology (EP) Procedures.
Phase: NA
Conditions: Cardiac Catheterization, Radiation Exposure
Sponsor: Corewell Health East

TITLE:  
Title: REDuce Radiation Exposure in Fluoroscopic 
INterventions Evaluation (REDEFINE)
NCT04404257 
Approval date: 07/14/2021 
Protocol and Statistical Analysis Plan

REDEFINE
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Title: REDuce Radiation Exposure in Fluoroscopic INterventions Evaluation (REDEFINE)
Investigational Plan
Version 12.0
5/26/2021
IRB Approved 7/14/2021 
Principal Investigator:
Simon R. Dixon, MBChB, FACC
Chair, Department of Cardiovascular Medicine 
Beaumont Hospital Royal Oak, Royal Oak, MI 
Dorothy Susan Timmis Endowed Chair Cardiology
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Table of Contents
1.0
Protocol Summary
2.0
Background
2.1
Current Approaches for Radiation Protection
2.2
ControlRad System
2.3
Pre-Clinical Data
3.0
Study Design
3.1
Objectives
3.2
Design
3.3
Study Population
3.4
Inclusion Criteria
3.5
Exclusion Criteria
3.6
Study Endpoints
3.7
Definitions
4.0
Conduct of Study
4.1
Screening
4.2
Informed Consent
4.3
Randomization
4.4
Measurement of Radiation Dose
4.5
Cath Lab Settings
4.6
Catheterization Procedure
4.7
Follow-up
5.0
Data Management
5.1
Data Collection
5.2
Calculation Effective Radiation Dose
5.3
Power Analysis
5.4
Blinding
5.5
Statistical Analysis
6.0
Risk Analysis
6.1
Risks/Benefits to Physicians/Staff
6.2
Risks/Benefits to Patient
7.0
References
8.0
Appendices
8.1
Study Flow Diagram
9.0
Tables
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1.0
Protocol Summary
Title
A prospective, randomized evaluation of the ControlRad system to 
reduce radiation exposure during cardiac catheterization and 
electrophysiology procedures
Design
Prospective, randomized, single center evaluation
Procedure
40 cardiac interventional procedures and 120 pacemaker and/or ICD 
procedures
Objective
To determine whether the ControlRad system reduces radiation 
exposure to operators, staff and patients during diagnostic and 
interventional cardiac catheterization procedures and electrophysiology 
implant procedures
Enrollment
Prospective
Site(s)
Beaumont Hospital Royal Oak
Time Course
2020- 2021
Primary Outcome
Effective radiation dose to primary operator
Principal Investigator
Simon R. Dixon, MBChB
Co-Investigators
Cheryl Schultz, Scott Emerson, Nishaki Mehta Study Coordination
Beaumont Hospital Royal Oak
2.0
Background
2.1
Current Approaches for Radiation Protection
Long-term radiation exposure in the cardiac catheterization laboratory is associated 
with an increased risk of premature cataract formation, chromosomal damage, 
subclinical atherosclerosis and cancer (1-4). Conventional approaches to limit radiation 
exposure include a) wearing lead apparel, b) positioning table and ceiling-mounted 
radiation shields between the operator and patient, and c) technical considerations such 
as reducing the fluoroscopic frame rate, minimizing fluoroscopic time and acquisition 
runs, maintaining the optimal table height and image intensifier position, and use of 
filters and collimators in the imaging chain (5,6). 
Despite these approaches, physicians working in the cardiac catheterization laboratory 
continue to receive high doses of radiation, primarily attributable to scatter radiation 
from the patient. This situation has in part been compounded by the increasing 
complexity of therapeutic procedures, such as interventions for chronic total occlusion. 
Prior studies have demonstrated that the primary operator is subject to the highest 
radiation dose due to proximity to the primary radiation beam, but other operators and 
staff also receive significant occupational exposure. Because of these concerns, there 
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has been a clear need to develop new methods to reduce radiation exposure to 
physicians and staff in the cardiac catheterization laboratory.
2.2
ControlRad System
ControlRad has developed a novel technology to reduce radiation exposure during 
cardiac catheterization procedures. The system uses a dynamic collimator that is 
installed above the X-ray tube of the cath lab system (Figure 1). The collimator is 
composed of a partially X-ray attenuating plate with a non-attenuating aperture 
corresponding to the region of interest. The attenuating plate is controlled by a number 
of motors to support high-speed motion of the plate. The position of the aperture is 
controlled by the physician using a table-mounted touch pad (Figure 2). Image 
processing software is used to match brightness and contrast in the attenuated and 
non-attenuated zones. The portion of the image seen through the aperture receives 
normal radiation dose, whereas the portion seen through the attenuated zone receives 
less radiation (Figure 3). For example, during a mid-LAD intervention, the aperture can 
be placed to maintain normal fluoroscopic image quality over the region of interest with 
a lower resolution over the remainder of the screen. The ControlRad system reduces 
radiation exposure during fluoroscopy, but does not change the dose during 
cineangiography.
Figure 1: ControlRad system mounted above X-ray tube
Figure 2: Table side touch pad
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Figure 3: Illustration of ControlRad System
2.3
Pre-Clinical Data
The ControlRad system was evaluated in a swine model of iliac and renal artery stenting 
(7). Radiation dose measurements were obtained with and without the ControlRad 
system. 
As shown below, there was a significant reduction in baseline radiation dose to both the 
operator and animal with the ControlRad system. The overall effect was a radiation 
reduction of approximately 75% relative to baseline dose. 
Without
With
p-value
Total kerma air product (Gym2)
635
124
<0.001
Total air kerma (mGy)
3394
1061
<0.001
Dosimeter (mR/h)
20.5
6.3
<0.001
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3.0
Study Design
3.1
Objectives
To determine whether the ControlRad system reduces radiation dose to operators, staff 
and patients during diagnostic and interventional cardiac catheterization and 
electrophysiology (EP) implant procedures
3.2
Design
Prospective, randomized single center evaluation
3.3
Study Population
-
Patients scheduled for cardiac catheterization in cath lab 5 at Beaumont Royal Oak.
-
Enrolment will continue until 40 patients undergoing intervention have been 
recruited. (The total patient population is estimated to be 200 given the current 
diagnostic cardiac catheterization to interventional cardiac catheterization case 
ration is 2:1 which may fluctuate more participants are enrolled.)
-
EP patients scheduled for a Pacemaker or ICD in cath lab 5 at Beaumont Royal Oak 
Hospital.  Enrollment will continue until 30 patients undergo a complex procedure in 
the EP lab. (The current patient population is estimated to be 120 given the simple 
to complex case ratio which may fluctuate as more participants are enrolled.) 
-
Physicians and staff 
o
For each procedure, 3 staff members will be study subjects: a) the primary 
operator, b) the secondary operator, c) the nurse/tech who circulates in the 
room 
o
Different operators and staff may participate in each case depending on 
cath lab scheduling. The cath lab has 20 cardiology fellows, 35 
interventional cardiologists and 56 staff, all of whom may participate in the 
study 
3.4
Inclusion Criteria
Subjects will be eligible to participate if the following criteria are met:
-
Patient
o
Scheduled to undergo left heart catheterization with angiography, and/or 
percutaneous coronary intervention
o
Scheduled to undergo pacemaker or ICD implant
o
EP device upgrade
o
Able to provide written informed consent prior to the procedure
o
Age ≥18 years
-
Physicians and Staff
o
Able to provide consent for the study
3.5
Exclusion Criteria
Subjects will not be eligible to participate if any of the following criteria are met:
-
Patient
o
Cardiogenic shock 
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o
Reason for cath procedure is pericardiocentesis
o
Subcutaneous ICDs
o
Lead revisions
o
Inability to provide informed consent
o
Pregnant
-
Physicians and Staff
o
Those who are not willing to participate in the study
3.6
Study Endpoints
Primary Endpoint
-
Mean effective radiation dose (μSv) to the primary operator 
Secondary Endpoints
-
Mean effective radiation dose (μSv) to the secondary operator 
-
Mean effective radiation dose (μSv) to the circulating nurse 
-
Mean radiation dose to the patient (dose-area product, DAP)
-
Mean radiation dose (μSv) at a standard location on the wall of the cath lab
3.7
Definitions
-
Primary operator is the physician who usually stands nearest to the C-arm. This is 
generally the attending physician in the EP cases and a fellow in cath lab 
-
Secondary operator is the physician or scrub assistant (nurse or technician) who 
typically stands to the right of the primary operator and in most cases is the 
attending physician in the cath lab. 
-
Nurse or Anesthesia team  typically circulates in the room and is responsible for 
monitoring the patient, administering medications and obtaining equipment for the 
procedure
4.0
Conduct of Study
4.1
Screening
Patient
-
All patients who are scheduled for cardiac catheterization in Cath Lab 5 will be 
considered for inclusion in the study. 
Physicians and Staff
-
Physicians and staff who work in Cath Lab 5 will be considered for participation in 
the study.
 
4.2
Informed Consent
Patient
-
Written informed consent will be obtained from the patient by the research 
coordinator or investigator.  
Physician and Staff
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-
Physicians and staff who work in Cath Lab 5 will be provided an information sheet 
regarding the study. The principal investigator will assist in informing the physicians 
and staff about the study, but will not participate in the consent process. Consent 
will be obtained by the research coordinator and will continue for the duration of 
the study. A physician or staff member may withdraw consent at any time during 
the study. Scheduling of procedures and staff will be determined by the cath lab 
manager/scheduler according to usual schedules and lab availability. If a patient, 
physician or staff member declines participation, the procedure will be scheduled in 
another cath lab. 
4.3
Randomization
Procedures will be randomized 1:1 using sealed envelopes provided by the study 
statistician to either cardiac catheterization without ControlRad or cardiac 
catheterization with the ControlRad system. The same 1:1 randomization process will be 
applied to the EP patient population. Patients will be blinded to the randomization. 
4.4
Measurement of Radiation Dose
Two methods will be used to measure radiation dose during the catheterization 
procedure:
A.
Real-time Dosimeter Badge (RaySafe)
Real-time radiation exposure data will be collected using the commercially available 
RaySafe dosimetry system (RaySafe i3, Billdal, Sweden). This dosimeter provides the 
ability to measure radiation dose per case. 
B.
Landauer Luxel Aluminium Oxide Dosimeter Badges
The Landauer dosimeter badge will provide a cumulative radiation dose for each 
anatomic location. One set of badges will be used for cases performed with 
ControlRad, and one set for catheterization cases without ControlRad. 
C.
Dosimeter Badge Positions
Prior to each catheterization procedure the radiation badges will be placed at each 
location by the research coordinator, radiation safety officer, or trained cath lab 
staff member. The dosimeter badges will be removed at the end of each case.
The location of the badges is shown below: 
RaySafe
(Dose Per Case)
Landauer
(Cumulative Dose)
Primary Operator
Thyroid
Knee
Thyroid (2)
Inner (2)
Secondary Operator
Thyroid
Knee
Thyroid (2)
Inner (2)
Nurse
Thyroid
Knee
Thyroid (2)
Inner (2)
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Cath Lab
Wall
Wall (2)
The outer dosimeter badges will be placed on the left anterior side of the thyroid 
collar and the left ankle. The knee badge is affixed to the lower seam of the lead 
apron. 
The inner badges will be placed underneath the lead apparel over the left anterior 
chest. 
The cath lab dosimeters will be placed at standard location on the wall at the foot 
end of the cath lab table. 
For the Landauer dosimeters, two badges will be placed at each location (one badge 
as a backup). 28 badges will be required (14 with and 14 without ControlRad)
4.5
Radiation Settings in Lab
The frame rate for fluoroscopy will be 7.5 frames per second (fps) and 15 fps for 
cineangiography (these settings are currently the default in Lab 5).  
4.6
Catheterization Procedure and EP procedure
Cardiac catheterization, percutaneous coronary intervention, pacemaker and ICD 
implantation will be performed according to standard guidelines and clinical practice. 
The ControlRad is only used during fluoroscopy (the device is not used during “cine” 
acquisition runs). In the event use of the ControlRad device is felt to significantly 
diminish imaging quality outside the region of interest the device can be turned off. 
Standard of care views (typically orthogonal) will be performed after PCI to ensure there 
is no vessel injury. 
Each attending physician may perform 1-2 “roll-in” cases to train on the ControlRad 
system before randomizing patients in the study.  
4.7
Follow-Up
No clinical follow-up will be performed after the hospital stay since the primary 
endpoint is radiation dose measured in the cath lab. 
5.0
Data Management
5.1
Data Collection
Data will be collected in case report forms in the REDCap database. 
5.2
Effective Radiation Dose
The effective radiation dose per case (E) will be calculated using a single dosimeter 
method (8).
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5.3
Power Analysis
In 2017, the median total air kerma dose (TAK) for a diagnostic and PCI in Cath Lab 5 was 
460 mGy and 1577 mGy respectively. Approximately 50% of the TAK for a diagnostic or 
PCI procedure is from fluoroscopy and 50% from cineangiography. In pre-clinical studies 
the ControlRad system reduced radiation dose by 75% during fluoroscopy. 
Using PASS 14 Power Analysis and Sample Size Software (2015). NCSS, LLC. Kaysville, 
Utah, USA, ncss.com/software/pass, we found that 9 diagnostic patients and 6 PCI 
patients per arm would give us 80% power to detect that absolute difference of 20% 
with a 0.05 significance level. Allowing for some variation in the actual frequencies in 
this higher risk group of patients or any drop outs, we intend to enroll 30 patients per 
arm.
5.4
Blinding
The physicians and nurses will be blinded to the radiation dose received in each case. 
The radiation dose to each operator and nurse will be recorded after every case by the 
study coordinator or radiation safety operator.  
5.5
Statistical Analysis
Data will be analyzed on an intent-to-treat basis. Continuous variables will be reported 
as mean ± standard deviation, and where appropriate as median ± interquartile range. 
Analyses will be performed by a biostatistician using with SAS software for Windows 
version 9.3 (or higher). 
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6.0
Risk Analysis
6.1
Risks/Benefits to Physicians and Staff
In the standard of care arm of the study there is no additional risk or benefit to the 
physicians or staff. In the ControlRad arm there is no risk to the physician or staff 
however both may benefit from reduced radiation exposure.
6.2
Risks/Benefits to Patient
The decision how to treat the patient is at the discretion of the attending physician. The 
technical approach used for the cardiac catheterization procedure will not be affected 
by the ControlRad system. In the standard of care arm of the study there is no additional 
risk or benefit to the patient. In the ControlRad arm there the patient may benefit from 
reduced radiation exposure. In the ControlRad arm there may be slightly diminished 
visualization of surrounding structures (outside the region of interest) when the device 
is used during fluoroscopy. 
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7.0
References
1.
Ciraj-Bjelac O, Rehani MM, Sim KH, et al. Risk for radiation induced cataract for staff in 
interventional cardiology: is there reason for concern? Catheter Cardiovasc Interv 
2010;76:826–34
2.
Andreassi MG, Cioppa A, Botto N, et al. Somatic DNA damage in interventional cardiologists: 
a case-control study. FASEB J 2005;19:998–9.
3.
Andreassi MG, Piccaluga E, Gargani L, et al. Subclinical carotid atherosclerosis and early 
vascular aging from long-term low-dose ionizing radiation. J Am Coll Cardiol Intv 
2015;8:616–27.
4.
Roguin A, Goldstein J, Bar O, et al. Brain and neck tumors among physicians performing 
interventional procedures. Am J Cardiol 2013;111: 1368–72.
5.
Agarwal S, Parashar A, Ellis S, et al. Measures to reduce radiation exposure in a modern 
cardiac catheterization laboratory. Circ Cardiovasc Interv 2014;7:447-455.
6.
Madder RD, et al. Radiation exposure among scrub technologists and nurse circulators 
during cardiac catheterization. The impact of accessory lead shields. J Am Coll Cardiol Intv 
2018;11:206-12.
7.
Balter S, Simon D, Granada J, et al. Significant radiation reduction in interventional 
fluoroscopy using a novel eye controlled movable region of interest. Med Physicians 
2016;43:1531-8.
8.
National Council on Radiation Protection and Measurements. Use of personal monitors to 
estimate effective dose equivalent and effective dose to workers for external exposure to 
low-LET radiation. Report No. 122; 1995. ncrponline.org/publications/reports/ncrp-reports-
122/
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8.0
Tables
Table 1. Patient and Procedural Characteristics
Total
N= 60
ControlRad
N=
No ControlRad 
N=
p-value
Age
Weight
Height
BMI
BSA
Diagnostic
PCI
Radial
Femoral
Brachial
Procedure time 
(mins)
Fluoro time 
(min)
Detector size
SID
Fluoro frame 
rate
Flouro air kerma
Fluoro kVP
Fluoro mA
Cine frame rate
Cine magn size
Cine kVp
Cine mA
Total air kerma
DAP
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Table 2. Cumulative Radiation Dose Measured with Aluminum Oxide dosimeter badges (mrem)
Location
ControlRad
N=
No ControlRad 
N=
p-value
Operator 1
Thyroid
Inner
Operator 2
Thyroid
Inner
Anesthesia/Nurs
e
Thyroid
Inner
Cath Lab Fixed
Wall
Table 3. Mean Radiation Dose to Physicians and Nurse Measured with RaySafe Dosimeters (mrem)
ControlRad
N=
No ControlRad 
N=
p-value
Operator 1
Thyroid
Knee
Operator 2
Thyroid
Knee
Anesthesia/Nurs
e
Thyroid
Knee
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IRB APPROVAL DATE: 07/14/2021