Minimizing Radiographic Contrast Administration During Coronary Angiography Using a Novel Contrast Reduction System: A Multicenter Observational Study of the DyeVert™ Plus Contrast Reduction System
Conditions: Chronic Kidney Disease
Sponsor: Osprey Medical, Inc

 
 
Clinical Investigational Plan Synopsys &  
Statistical Analysis Plan 
taken from:   
 
 
 
Clinical Investigation Plan 
 
Observational evaluation of the DyeVert Plus™ System 
 
 
 
 
Osprey Medical Study Number: TP-6579 
 
Revision: 3.0 
Date: 06Jul2017 
 
NCT03715452 
 
 
 
Sponsor: 
Osprey Medical, Inc 
5600 Rowland Road, Suite 250 
Minnetonka, MN 55343 
USA 
 
Telephone: +1 952.955.8230 
Fax:  +1 952.955.8171 
 
 

Osprey Medical 
DyeVertTM Plus Trial  
TP-6579 
Clinical Investigational Plan 
 
 
Document Number: TP-6579 Final Version 3.0 
Page 11 of 29 
All contents of this document are confidential information belonging to Osprey Medical and may not be used for any purpose 
whatsoever without specific written consent from Osprey Medical. 
 
2 
CLINICAL INVESTIGATIONAL PLAN SYNOPSIS 
TITLE 
Observational evaluation of the DyeVert™ Plus System 
PROTOCOL 
NUMBER 
TP-6579 
STUDY PRINICIPAL 
INVESTIGATOR 
Hitinder S. Gurm, MD 
DEVICE 
EVALUATED 
The device evaluated in this trial is the Osprey Medical DyeVert Plus 
Contrast Reduction System (Model Numbers: CMW-XX and XVOFF-XXX) 
which consists of a Contrast Monitoring Wireless Display (CMW) and the 
DyeVert Plus Disposable Kit which is inclusive of a disposable single-use 
sterile Smart Syringe and DyeVert Plus Module.  
PURPOSE 
The purpose of this post-market observational study is to evaluate the 
DyeVert™ Plus System during standard clinical use and to quantify contrast 
media (CM) volume saved during manual injections in coronary angiography 
and interventional procedures.  
STUDY OBJECTIVES 
1. Evaluate the volume (percentage) of CM saved over the total procedure, 
performed with manual injections 
2. Assessment of incidence of Serious Adverse Device Effect  
STUDY DESIGN 
This is a prospective, single arm, multi-center, observational clinical study of 
the DyeVert Plus System. 
SUBJECT 
POPULATION 
Subjects undergoing a coronary artery imaging (angiogram) for diagnostic 
and/or percutaneous coronary intervention (PCI) procedures are eligible to 
participate in this study. 
TREATMENT 
GROUPS 
This is a single-arm observational study.  All enrolled subjects will have a 
coronary diagnostic imaging and/or PCI procedure conducted with the 
DyeVertTM Plus System. 
CLINICAL SITES 
This observational study will be conducted at up to 15 centers.  
STUDY DURATION 
There are no scheduled follow-up visits.  Subjects will be followed through 
discharge.  
SAMPLE SIZE 
This study will enroll 118 subjects. 
INCLUSION / 
EXCLUSION 
CRITERIA 
To be included in this study, subjects must meet all of the following criteria: 
1. The subject is ≥ 18 years of age 
2. The subject is indicated for a coronary angiogram or percutaneous 
coronary procedure 
3. The subject has baseline eGFR (as determined by the local laboratory) 
greater than or equal to 20 but less than or equal to 60 mL/min/1.73m2 
4. The subject is willing and able to provide appropriate informed consent. 
 Subjects will be excluded from this trial if they meet the following criteria: 
1. Subject is undergoing the procedure for the diagnosis of acute STEMI. 
Patients undergoing planned PCI to non-culprit vessel in a patient with 
recent STEMI and primary PCI (at least 24 hours prior) can be enrolled. 

Osprey Medical 
DyeVertTM Plus Trial  
TP-6579 
Clinical Investigational Plan 
 
 
Document Number: TP-6579 Final Version 3.0 
Page 12 of 29 
All contents of this document are confidential information belonging to Osprey Medical and may not be used for any purpose 
whatsoever without specific written consent from Osprey Medical. 
 
2. The subject is female and currently pregnant 
3. Subject is undergoing planned OCT analysis 
4. Subject is undergoing planned CTO intervention 
5. Subject has a planned TAVR within 72 hours of index procedure 
6. Subject has known coronary artery fistulas, or another condition known 
to require large volumes of contrast (>10mls) for each injection not 
allowing the possibility of contrast minimization 
7. Subject has a BMI >40 
8. In the investigator’s opinion, the subject is not considered to be a suitable 
candidate 
DATA COLLECTED 
At a minimum, the following subject data will be collected or reported: 
Pre-Procedure 
• 
Demographics 
o 
Age 
o 
Gender 
o 
Race and ethnicity 
• 
Vital Signs 
o 
Height 
o 
Weight 
o 
BMI (calculated) 
• 
Subject medical history inclusive but not limited to: 
o 
Previous Cardiovascular Disease History 
o 
Serum Creatinine/eGFR calculation  
o 
Diabetic Status 
o 
Anemia 
• 
Anticipated treatment plan 
Procedure Data 
• 
Overall procedure data: 
o 
Total time of procedure (first administration of CM to last 
administration of CM) 
o 
Access location 
o 
Catheter size/type 
o 
DyeVert Plus Disposable Kit (i.e. Smart Syringe and 
DyeVert Plus Module) Lot number 
o 
DyeVert Display (CMW) Serial number 
o 
CM brand/type/concentration(s)  
o 
Treatment type 
o 
Treated lesion details 
o 
Total fluoroscopy time 
o 
Additional imaging (e.g. FFR, IVUS, etc) 
o 
Contrast Media Information from CMW Unit: Cumulative 
Volume, Contrast Saved, percent Contrast Saved, set 
Threshold Volume amount, and percent of Physician 
Specified Threshold 
o 
Method of determining Threshold  
o 
Evaluation of treatment plan details 
o 
DyeVert System “Off” details: Reason system was turned 
off 
o 
Adverse Events  

Osprey Medical 
DyeVertTM Plus Trial  
TP-6579 
Clinical Investigational Plan 
 
 
Document Number: TP-6579 Final Version 3.0 
Page 13 of 29 
All contents of this document are confidential information belonging to Osprey Medical and may not be used for any purpose 
whatsoever without specific written consent from Osprey Medical. 
 
Procedure Follow Up/Study Exit 
• 
All standard of care Serum Creatinine/eGFR calculations collected 
prior to discharge 
• 
Reason for study exit 
STUDY TIMELINE 
All data will be collected through discharge.   

Osprey Medical 
DyeVertTM Plus Trial 
TP-6579 
Clinical Investigational Plan
 
 
Document Number: TP-6579 Final Version 3.0 
Page 22 of 29 
All contents of this document are confidential information belonging to Osprey Medical and may not be used for any purpose 
whatsoever without specific written consent from Osprey Medical. 
 
6 
DATA AND QUALITY MANAGEMENT 
6.1 Study Data Collection 
6.1.1 
Study Data Requirements 
To ensure data quality and completeness, all required data will be recorded within an electronic 
database (EDC) provided by Osprey Medical. 
6.2 Protocol Deviations 
A protocol deviation is defined as a circumstance in which the Investigator or other site personnel 
did not conduct the trial according to the protocol, applicable laws/regulations, or any study 
agreements (i.e. Clinical Trial Agreement or Investigator Agreement). 
Protocol Deviations will be documented on the Protocol Deviation eCRF. Protocol deviations are 
reportable to the Institution’s governing Institutional Review Board (IRB) during the annual 
reporting process, unless otherwise directed by the governing IRB requirements or as the specific 
circumstance dictates. 
6.3 Investigator Certification 
Osprey Medical certifies that the investigator will fully execute the Osprey Medical Investigator 
Agreement for this DyeVert Plus Trial. 
6.4 User Training 
Physician investigators will be specialists in interventional cardiology.  Primary users using the 
DyeVert Plus System will undergo training on set-up and use of the system. Auxiliary personnel, 
such as catheter laboratory technicians, may also be trained in system use. The training will include 
on-site training, but may also be supplemented with additional training. Training materials such as 
IFU and training presentations will be provided. All training will be conducted by Osprey Medical 
representatives and/or Osprey Medical-designated representatives.  If primary users have extensive 
use of the DyeVert product, training may be tailored to represent need-based training. 
7 
STATISTICAL METHODS AND DATA ANALYSIS 
7.1 Analysis of Primary Effectiveness Objective 
The primary endpoint of the study is the mean percentage of CM volume saved. Analysis will be 
based on a one sample t-test. The formal statistical test will be based on a one-sided t-test against a 
fixed null hypothesis. The null and alternative hypothesis to be tested is: 
Ho: 𝜇ௗ௜௩௘௥௧௘ௗ൑30%   
Ha: 𝜇ௗ௜௩௘௥௧௘ௗ൐30%  
where μdiverted is the mean percentage measured volume saved. Successful rejection of the null 
hypothesis will demonstrate that the percentage of volume saved is statistically greater than 30%.  

Osprey Medical 
DyeVertTM Plus Trial 
TP-6579 
Clinical Investigational Plan
 
 
Document Number: TP-6579 Final Version 3.0 
Page 23 of 29 
All contents of this document are confidential information belonging to Osprey Medical and may not be used for any purpose 
whatsoever without specific written consent from Osprey Medical. 
 
To account for the variation in contrast savings by procedure type, a supplementary analysis will be 
performed using a model to adjust for procedure type (PCI vs diagnostic). An additional analysis 
adjusting for physician will also be employed if deemed appropriate based on number of physicians 
and number of cases per physician.  
7.1.1 
Sample Size Considerations 
The mean total contrast volume saved is expected to be at least 35%. Based on a sample size of 100 
subjects and a one-sided 0.025 alpha level, greater than 80% power will be provided for a standard 
deviation of 16. A larger mean or smaller standard deviation would provide additional power.  
To account for the possibility of unavailable contrast savings data or incorrect usage of the device, 
a 15% attrition rate will be utilized. A total of 118 subjects will be enrolled to obtain approximately 
100 evaluable subjects.  The following instances indicate subjects deemed unevaluable for the 
primary analysis. 
 
The DyeVert Reservoir was inadvertently turned off due to user error for > 1 injection. 
 
The DyeVert Reservoir was turned OFF for >1 injection due to an adverse event, not 
related to the device. 
 
The CMW did not provide contrast accounting details at the end of a case due to device 
deficiency.  
 
A contrast accounting error due to user error occurs for > 1 injection as defined in the 
procedure case report form.  
 
The treating physician determines that a blue tooth disconnection occurred resulting in 
inaccurate contrast accounting.  
7.2 Subgroup Analyses  
A subgroup analysis of the primary endpoint will be performed based on access approach (radial 
versus femoral), body mass index (BMI), physician user and procedure type.  For BMI, subgroups 
will be defined those with BMI < 30 kg/m2 versus those ≥ 30 kg/m2. A two-sample t test will be 
performed to compare the primary endpoint between groups at the nominal 0.05 alpha level.  For 
grouping physicians in more than two groups, an ANOVA model will be used.   
7.3  Additional Statistical Considerations  
The primary analysis of endpoints will be based on the population of subjects with evaluable data 
for that endpoint. Cases deemed unevaluable in the primary analysis will be summarized in a 
listing and a second analysis will be performed inclusive of these cases. Sensitivity analyses for 
missing data may be performed if warranted. In the event normality assumptions of statistical 
models are not met, logarithmic transformations or non-parametric methods will be employed. All 
data will be summarized by descriptive statistics, using the mean, standard deviation, median, inter-
quartile range, or percentages, numbers of patients with events, etc. and the associated 95% 
confidence intervals, as appropriate.