ivWatch Sensor: Device Validation for Infiltrated Tissues
Phase: NA
Conditions: Infiltration of Peripheral IV Therapy
Sponsor: ivWatch, LLC

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
1 of 58 
 
 
 
 Clinical Investigational Plan 
 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues  
 
 
William J. Naramore 
Susan Brown, MSN, MSED, BA, VA-BC 
Gregory J. Schears, M.D. 
Marisa A. Cole 
  
 
ivWatch, LLC  
469 McLaws Circle 
Williamsburg, VA 23185 
 Version Date: March 12, 2019 
 
ClinicalTrials.gov NCT Number: NCT04064229 
 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
2 of 58 
Table of Contents 
General Information ..................................................................................................... 5 
Rationale and Background .......................................................................................... 6 
ivWatch Model 400 Clinical Studies ...................................................................................... 8 
ivWatch SmartTouch Sensor Clinical Study Plan ................................................................. 9 
Infiltration Detection by the Perfect Clinician ................................................................... 10 
Study Goals and Objectives ...................................................................................... 18 
Study Design ................................................................................................................ 18 
Methodology ............................................................................................................... 23 
Subject Recruitment .............................................................................................................. 23 
Preliminary Information and Consent ................................................................................. 24 
Data Collection ...................................................................................................................... 25 
Subject Preparation ............................................................................................................... 25 
Data Collection ...................................................................................................................... 26 
End of Study ............................................................................................................................. 26 
Data Analysis ......................................................................................................................... 27 
Risk Benefit Analysis .................................................................................................... 27 
Injection of Isotonic Saline ................................................................................................... 27 
The ivWatch Technology ...................................................................................................... 28 
Follow-Up ..................................................................................................................... 30 
Data Management and Statistical Considerations ................................................. 30 
Data Management ................................................................................................................ 30 
Statistical Considerations...................................................................................................... 31 
Primary Objective ................................................................................................................... 31 
Secondary Objectives ........................................................................................................... 33 
Quality Assurance ....................................................................................................... 35 
Monitoring Plan ........................................................................................................... 35 
Expected Outcomes of the Study ............................................................................. 36 
Publication Policy........................................................................................................ 36 
Duration of the Study .................................................................................................. 36 
Anticipated Problems ................................................................................................. 36 
Ethics ............................................................................................................................ 36 
Good Clinical Practice ............................................................................................... 36 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
3 of 58 
Clinical Trial Insurance ............................................................................................... 37 
Informed Consent Forms ............................................................................................ 37 
Deviations from the Protocol ...................................................................................... 37 
Serious Adverse Events / Device Deficiencies ......................................................... 37 
Case Report Form ....................................................................................................... 38 
Pre-Screening Form .................................................................................................... 41 
Health History Form ..................................................................................................... 43 
Skin Pigmentation Worksheet .................................................................................... 44 
Pre-Study Checklist ..................................................................................................... 46 
Data Collection Checklist .......................................................................................... 47 
FDA Clearance Letters for ivWatch Model 400 ........................................................ 51 
Investigator Signatures ............................................................................................... 55 
Statistical Monte Carlo Analysis ................................................................................ 56 
Bibliography ................................................................................................................ 58 
  
Figures 
Figure 1. ivWatch Model 400 Infiltration Monitoring System ................................................................... 7 
Figure 2. ivWatch Model 400 with Extension Module and SmartTouch Sensor .................................... 8 
Figure 3. The sensitivity of a perfect clinician for identifying early infiltrations (infiltrated volume < 
10mL). ............................................................................................................................................................ 11 
Figure 3. Pre-study measurements performed on each subject. ........................................................ 19 
Figure 5. The four possible anatomical sites monitored during this study. .......................................... 19 
Figure 6. The Sonosite S-Series commercial ultrasound imaging system. ........................................... 21 
Figure 7. Example of the ivWatch SmartTouch sensor ........................................................................... 22 
Figure 8. The ivWatch Patient Monitor with extension module and user interface elements. ........ 23 
Figure 9. The Monte Carlo simulation of a device operating with an infiltration sensitivity equivalent 
to the perfect clinician (null hypothesis) and a device operating at a 90% sensitivity (alternative 
hypothesis). The red line shows the location of α=0.041 threshold (one-sided). ............................... 32 
Figure 10. The statistical power for a 98 PIV site study as a function of the device sensitivity (specific 
alternative hypothesis). .............................................................................................................................. 33 
Figure 11. Statistical power vs sample size for detection volume comparison .................................. 34 
Figure 12. Examples of confidence intervals at various ST sensitivities, assuming FO sensitivity = 96%.
 ........................................................................................................................................................................ 35 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
4 of 58 
 
Tables 
Table 1. The recommended site assessment frequency by the Infusion Nurses Society. ................ 11 
Table 2. Clinical studies performed with the ivWatch Model 400 device. ......................................... 12 
Table 3. Clinical studies performed with SmartTouch sensor. ............................................................... 15 
Table 4. The study configuration. .............................................................................................................. 20 
Table 5. List of study exclusion criteria. ..................................................................................................... 24 
Table 6. Clinical trials involving the ivWatch technology. ..................................................................... 29 
Table 7. The study configuration for the infiltration study ...................................................................... 31 
 
Project Summary 
Peripheral intravenous (PIV) therapy is one of the most common invasive procedures performed 
in US hospitals. PIV failures often occur when fluids leak out of the vein into surrounding tissue. This 
failure is called an infiltration for the leakage of non-vesicant solutions or an extravasation for 
vesicant solutions. The ivWatch Model 400 is a device that assists medical professionals in 
monitoring patients for PIV infiltration and extravasation events using an optical sensor. This device 
received FDA clearance for use in the adult and pediatric age groups in February 2015 and 
December 2016, respectively. The corresponding FDA letters are included on Page 51.  
ivWatch is enhancing the Model 400 to support a new disposable electronic sensor, called 
SmartTouch. In this study, the SmartTouch sensor cable will be tested to show equivalence to the 
original Model 400 fiber optic sensor. The new sensor design includes optical components in the 
sensor package, similar to a typical pulse oximeter. This design allows the sensor to be lower cost 
and disposable. The goal of this study is to validate the performance of the ivWatch SmartTouch 
sensor  for detecting the early stages of an IV infiltration, as collected from healthy adult 
volunteers. The Model 400 Fiber Optic sensor is used for performance comparison.  
The study objectives include: 
Primary Objective: Demonstrate a statistically significant improvement for detecting early stage 
infiltrations in comparison to hourly observation by a perfect clinician. 
Secondary Objectives: 
1. Demonstrate statistical equivalence in infiltration detection volume of the SmartTouch and 
Fiber Optic sensors. 
2. Demonstrate statistical equivalence in infiltration sensitivity of the SmartTouch and Fiber 
Optic sensors. 
 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
5 of 58 
General Information 
Protocol Title:  
ivWatch SmartTouch Sensor: Device Verification for Infiltrated Tissues  
Name and Address of Sponsor: 
Corporate Location 
ivWatch, LLC 
 
1100 Exploration Way 
Suite 209 
 
Hampton, VA 23666 
 
1.855.489.2824  
  
 
Research and Development Location 
ivWatch, LLC 
 
469 McLaws Circle 
 
Williamsburg, VA 23185 
 
1.855.489.2824  
 Name and Title of Investigators: 
William J. Naramore, Chief Technology Officer, Principal Investigator 
Susan Brown, MSN, MSED, BA, VA-BC, Chief Nursing Officer 
Gregory J. Schears, M.D., Consultant serving as Chief Clinical Officer 
Marisa A. Cole, Biomedical Engineer 
All investigators work at ivWatch, LLC and have the following address and phone number. The 
clinical study will take place at this location. 
Research and Development Location 
ivWatch, LLC 
 
469 McLaws Circle 
 
Williamsburg, VA 23185 
 
1.855.489.2824  
 
 
 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
6 of 58 
Rationale and Background 
Peripheral intravenous (PIV) therapy is one of the most common invasive procedures performed 
in US hospitals. Over 25 million patients, or approximately 80% of hospital patients, require 
intravenous therapy each year in the United States [1]. Despite widespread use, a number of 
potential complications can occur during PIV therapy.  Infiltration is the most common mode of 
PIV catheter failure, with an average incidence rate of 23.9% according to a prospective 
randomized review of controlled studies from 1999 to 2014 [2]. The other common modes of failure 
are catheter occlusion / mechanical failure (18.8%), catheter-related phlebitis (15,4%), catheter 
dislodgement (6.9%), and catheter-related infection (0.2%) [2]. A multicenter trial indicated 
infiltrations occurred 27-32 times per 1000 intravenous catheter days in adults [3].  Infiltration is the 
leakage of non-vesicant fluids like saline into the surrounding tissue. Extravasation is the leakage 
of vesicant fluids, which include cytotoxic drugs, intravenous nutrition, and calcium, potassium, 
and bicarbonate solutions [4].  
IV infiltration or extravasation is usually accompanied by pain, erythema, and/or edema in the 
vicinity of the insertion site. Severe infiltration and extravasation may lead to necrosis requiring skin 
debridement, skin grafting, or amputation [5]. One common area of malpractice lawsuits filed 
against physicians and nurses involves infiltration or extravasation [6]. It has been reported that 
the infiltration rate for contrast media injections is independent of infusion rate and it does not vary 
significantly with regard to injection site, catheter size, or catheter type [7]. A randomized 
controlled trial including 3,283 adult medical and surgical patients with 5,907 total catheters 
indicated that PIV catheter occlusion rate (including infiltration) is improved by forearm insertion 
versus hand, antecubital fossa, or upper arm [8]. The reported incidence of infiltration in the 
neonatal intensive care unit (NICU) population is between 23% and 78% and carries the potential 
for long-term sequelae [9].  
ivWatch, LLC has developed the ivWatch Model 400 – a Class II medical device that is cleared for 
use on adults and pediatrics. The ivWatch Model 400 is indicated for the detection of 
subcutaneous infiltrations and extravasations of 10 cc or less of optically clear infusates, as an 
adjunctive device to the clinical evaluation in the healthcare setting of adults and pediatrics with 
PIVs.  
The ivWatch Model 400 consists of the ivWatch Patient Monitor (IPM), reusable fiber optic sensor 
cable, and sensor cable receptacle. As illustrated in Figure 1 below, the reusable fiber optic sensor 
delivers visible and near-infrared light to the tissue and transmits reflected light back to the IPM. 
The IPM contains an optical system that generates light signals that are sent to the patient’s skin 
(via the reusable fiber optic sensor cable), and measures the light returning from the patient’s skin 
(also via the reusable fiber optic sensor cable).  The sensor head of the reusable fiber optic sensor 
cable is held in place and attached to the patient using the sensor receptacle. The IPM also 
contains the hardware for executing the proprietary ivWatch signal processing algorithm, and for 
displaying system status on a user interface, including audible and visual notifications indicating 
changes to the state of the PIV. 
When changes in the diffuse reflectance in the tissue near the peripheral IV insertion site are 
consistent with an infusate pooling in the subcutaneous tissue, the IPM emits audible and visual 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
7 of 58 
notifications intended to prompt the clinician to inspect the peripheral IV site for a possible 
infiltration event.  Prompt identification of infiltrations reduces the risk of injury to patients 
undergoing peripheral IV therapy and improves the likelihood of receiving the correct dosage of 
medications delivered intravenously. 
 
Figure 1. ivWatch Model 400 Infiltration Monitoring System 
The ivWatch Model 400 system has been expanded to support both the fiber optic sensor cable 
configuration of the existing Model 400 as well as an electronic sensor cable configuration 
(SmartTouch). The SmartTouch sensor consists of low-cost optical components built into the sensor 
head, like disposable pulse oximeter sensors. This design allows the SmartTouch sensor to be a 
more cost effective single-use sensor, as opposed to the costlier reusable fiber optic sensor. An 
extension module compatible with the existing ivWatch Model 400 was developed to support an 
electronic sensor cable configuration, (Figure 2). The Extension Module is connected to the IPM 
via USB. The SmartTouch sensor was designed to be an electronic version of the Model 400 fiber 
optic sensor. The sensor is placed on the skin of a patient near the PIV site, following the protocol 
as the Model 400, and the same indications for use apply. 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
8 of 58 
 
Figure 2. ivWatch Model 400 with Extension Module and SmartTouch Sensor 
ivWatch Model 400 Clinical Studies 
The ivWatch Model 400 was tested in a series of IRB-approved studies on healthy adult research 
subjects, as summarized in Table 2. The Design Verification studies evaluated the performance of 
the device under different conditions. The NIR Detection of PIV Infiltration study evaluated two 
models of PIV infiltration as well as potential algorithm correction for changes in tissue blood 
volume. The Signal Variation of Normal Tissue study evaluated the sources and rates of non-
infiltration alarms when monitoring normal, non-infiltrated tissues. In this protocol document, the 
terms ‘alarm’ and ‘notification’ are considered interchangeable. Two clinical studies evaluated 
how the infiltration rate and catheter depth affected the diagnostic performance of the ivWatch 
Model 400. The device detected all 10mL infiltrations for common adult infusion rates ranging from 
5 mL/hr to 150 mL/hr. The device detected all infiltrations with a catheter depth less than 5 mm 
deep although deeper infiltrations caused a reduced sensitivity by the device. The final study 
assessed the adhesion of the ivWatch receptacle over a 96 hour period. There were no adhesion 
issues with the receptacle when used with an occlusive dressing. 
After completing the design verification studies, two additional studies were performed to validate 
the final design. The study, titled Device Validation for Non-Infiltrated Tissues, evaluated non-
infiltrated sites over a 24 hour period. The device issued a false red notification once every 4.2 
days and a false yellow notification once every 2.0 days. These notifications were often caused 
by compression of the IV site. The next study, titled Device Validation for Infiltrated Tissues, 
evaluated the performance of the ivWatch Model 400 for detecting 140 infiltrated IV sites. Of the 
140 IV sites, the ivWatch device issued 135 red notifications (96% sensitivity) and 139 yellow 
notifications (99% sensitivity). These results demonstrated the ivWatch Model 400 is highly sensitive 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
9 of 58 
to infiltrated PIV sites on the hands and forearms of adults while having a false notification rate 
that should have negligible effects on clinical alarm fatigue. 
Three additional IRB-approved studies were performed to (1) examine the infiltration detection 
performance as a function of the distance separating the catheter tip and ivWatch sensor, (2) 
examine the infiltration detection performance when the sensor is placed above and below a 
transparent occlusive dressing, and (3) examine the false notification rate when the sensor is 
placed above a transparent occlusive dressing. 
After the FDA clearance for ages 18 and up, an IRB-approved clinical study was conducted to 
measure the performance of the ivWatch Model 400 device for detecting early stage infiltrations 
on pediatric patients at Cincinnati Children’s Hospital Medical Center. Hospitalized pediatric 
patients under the age of 18 who received continuous IV therapy were monitored with the device. 
The study was broken into two groups, 156 subjects in a blinded non-alarming group, and 57 
subjects in an alarming group. The objectives of the study were to determine the amount of time 
between infiltration detection by the clinician and the device as well as the device sensitivity and 
specificity. Each site was continuously monitored during IV therapy and the IV was terminated if 
an infiltration was detected or other complications were identified. In the nonalarming group, the 
device issued red “Check IV” notifications a median time of 15.2 hours before clinician detection. 
The device issued notifications for 18 out of 23 clinician-confirmed infiltrations in the non-alarming 
group, for a sensitivity of 78.3%. In the alarming group, the device issued notifications for 12 out of 
15 clinician-confirmed infiltrations. The results from this study were used to support the FDA 
clearance for all age groups including pediatrics in December of 2016. 
ivWatch SmartTouch Sensor Clinical Study Plan 
A series of new clinical studies are taking place to test feasibility as well as to verify and validate 
the SmartTouch sensor in a similar way to the Model 400. Two feasibility studies were completed 
to examine the ‘alpha’ design of the SmartTouch sensor in terms of (1) infiltration signal 
performance and (2) false notification rate of the SmartTouch sensor (Table 3). These studies have 
indicated the optical design of the alpha SmartTouch sensor performs equivalently to the Model 
400 fiber optic sensor. Four verification studies were performed to test the ‘beta’ SmartTouch 
design and show equivalence to the Model 400 in terms of (1) device sensitivity and (2) false 
notification rate. The beta SmartTouch design contains the same optical sensor as alpha, but 
improvements were made to the sensor for increased durability and manufacturability. Signal 
data from these verification studies may be used to improve signal processing algorithms prior to 
final software design.   
This clinical protocol is the validation study that will examine the infiltration sensitivity performance 
of the ivWatch SmartTouch sensor versus the Model 400 fiber optic sensor. This study is modeled 
after the clinical protocol used to validate the Model 400 system, Device Validation for Infiltrated 
Tissues (Table 2). The primary objective of the study is to demonstrate a statistically significant 
improvement for detecting early stage infiltrations in comparison to hourly observation by a 
perfect clinician, the current clinical standard. The secondary objectives are to demonstrate 
statistical equivalence in (1) infiltration detection volume and (2) infiltration sensitivity of the 
SmartTouch and Fiber Optic sensors. 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
10 of 58 
Infiltration Detection by the Perfect Clinician 
To be an effective product, the ivWatch sensors must detect early stage infiltrations significantly 
better than the current nursing standard of care. To facilitate this comparison and provide 
conservative estimates of the device performance, the idea of a perfect clinician is used, that is, 
a clinician who assesses the IV site hourly and perfectly classifies the IV site as normal or infiltrated, 
regardless of how much fluid has been infiltrated into the tissue. 
The primary metric used to compare the performance of the ivWatch device with the perfect 
clinician is the early infiltration sensitivity. The infiltration sensitivity is the percentage of early stage 
infiltrations (<10mL) detected by the ivWatch device or the perfect clinician. For the ivWatch 
device, the infiltration sensitivity is the ratio of the sites that generate a red alarm to the total 
number of monitored sites. For the perfect clinician, the infiltration has the same probability of 
occurring at any time between clinical assessments. Consequently, the percentage of infiltrations 
detected by the perfect clinician prior to 10mL of infiltrated volume is given by 
S𝐶𝐶= min (100%, 𝑉𝑉𝑙𝑙𝑙𝑙𝑙𝑙
𝑅𝑅∙𝑇𝑇𝐶𝐶
∗100%) 
where Vlim (mL) is the 10mL volume limit, R (mL/hr) is the infiltration rate, and TC is the observation 
period (hr). For example, at 100 mL/hr (R=100), the perfect clinician making hourly assessments 
(TC=1) of the site would be expected to detect 10% (Clinician Sensitivity = SC) of the infiltrations 
prior to 10mL (Vlim=10).  
Figure 3 illustrates the infiltration sensitivity of a perfect clinician for different infiltration rates and 
observation periods. A highlighted box indicates common adult infusion rates. The performance 
of the perfect clinician is limited by how frequently the site can be assessed. If the perfect clinician 
could monitor the site continuously (observation period = 0), the clinician’s infiltration sensitivity 
would be perfect. 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
11 of 58 
 
Figure 3. The sensitivity of a perfect clinician for identifying early infiltrations (infiltrated volume < 
10mL). 
The frequency of IV site assessments can vary significantly in practice depending on the clinician’s 
workload and the perceived risks to the patient. Table 1 includes the assessment frequency 
recommended in a position paper published by the Infusion Nurses Society [10]. Discussions with 
clinicians suggest most peripheral IV sites are checked either once per hour or less frequently. As 
described later, the primary statistical objective in this validation study was performed assuming 
hourly observation by a perfect clinician. 
Table 1. The recommended site assessment frequency by the Infusion Nurses Society. 
Assessment Frequency 
Description 
At least every 4 hours 
• 
Patients who are receiving nonirritant/nonvesicant 
infusions and who are alert and oriented and who are 
able to notify the nurse of any signs of problems such as 
pain, swelling, or redness at the site. 
At least every 1 to 2 hours 
• 
Critically ill patients 
• 
Adult patients who have cognitive/sensory deficits or 
who are receiving sedative-type medications and are 
unable to notify the nurse of any symptoms 
• 
Catheters placed in a high-risk location (e.g., external 
jugular, area of flexion) 
At least every hour 
• 
Neonatal patients 
• 
Pediatric patients 
More frequently (every 5 
to 10 minutes) 
• 
Patients receiving intermittent infusions of vesicants 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
12 of 58 
Table 2. Clinical studies performed with the ivWatch Model 400 device. 
Study 
Purpose 
Outcome 
Key Performance Metrics 
NIR Detection of PIV 
Infiltration  
ivWatch Study ID: IVWRSCS-01 
Chesapeake IRB ID: 00008513 
Number of Subjects: 24 
Number of Sites: 48 
Dates: June-August 2013 
 
1. Investigate in vivo model of 
subcutaneous injections near 
vascular bundles as substitute to 
through vein infiltrations. 
2. Validate sensor and receptacle 
designs. 
3. Investigate and validate effect of 
tissue blood volume changes on 
signal. 
• Subcutaneous injections are 
more challenging to detect. 
• Validated the sensor and 
receptacle designs. 
• Insensitive to changes in the 
tissue blood volume. 
 
Diagnostic Performance  
(all, subcutaneous, through-vein): 
• Sensitivity: 90%, 83%, 96% 
• Specificity: 100%, 100%, 100% 
Detected Volume 
• Through-Vein: 2.0mL 
• Subcutaneous: 3.3mL 
The Signal Variation of 
Normal Tissue  
ivWatch Study ID: IVW400CS-
01 
Chesapeake IRB ID: 00008218 
Number of Subjects: 30 
Number of Sites: 30 
Dates: August-November 2013 
1. Identify sources of non-infiltration 
alarms. 
2. Estimate rates of non-infiltration 
alarms for patients in an environment 
that mimics a hospital room. 
3. Investigate potential interference 
between other near infrared devices. 
• Negligible impact on clinical 
alarm fatigue. 
• Non-infiltration alarms 
generated by tissue 
deformation. 
• No infiltration alarms due to 
device interference. 
Red Alarm Rate:  
• 0.11 red alarms / day 
• 3 alarms in 661 hours 
Yellow Alarm Rate:  
• 0.40 yellow alarms / day 
• 11 alarms in 661 hours 
The Effect of Catheter 
Depth 
ivWatch Study ID: IVW400CS-
02 
Chesapeake IRB ID: 00008254 
Number of Subjects: 28 
Number of Sites: 56 
Dates: September-October 
2013 
1. Determine relationship between 
infiltration depth and ivWatch 
sensitivity. 
2. Investigate tissue characteristics that 
affect ivWatch performance. 
• Validation of optical modeling. 
• ivWatch sensitivity greatest for 
infiltration depths < 5mm. 
• Presence of a fascia interposed 
between catheter tip and 
sensor reduces sensitivity. 
Depths Less than 5mm (On-
Design) 
• 1-3mm Deep: 100% sensitive 
(12/12) 
• 3-5mm Deep: 100% sensitive 
(17/17) 
Depths Greater than 5mm (Off-
Design): 
• 5-7mm Deep: 38% sensitive (5/13) 
• 7-9mm Deep: 50% sensitive (7/14) 
 
The Effect of Infiltration Rate 
ivWatch Study ID: IVW400CS-
03 
Chesapeake IRB ID: 00008941 
Number of Subjects: 24 
Number of Sites: 48 
Dates: October-November 
2013 
1. Determine volumes of infiltration fluid 
required to generate alarm as a 
function of infiltration flow rate. 
2. Determine times required to 
generate an alarm as a function of 
infiltration flow rate. 
• Detected all infiltrations 
regardless of infiltration rate. 
• The response time of the system 
strongly determines the 
detected volume when the 
device alarms. 
Sensitivity & Median Detected 
Volume 
• 5mL/hr: 100% (12/12) and 0.9mL 
• 50mL/hr: 100% (12/12) and 2.2mL 
• 100mL/hr: 100% (12/12) and 3.7mL 
• 150mL/hr: 100% (12/12) and 5.7mL 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
13 of 58 
Long Term Adhesion of the 
ivWatch Receptacle 
ivWatch Study ID: IVW400CS-
04 
Chesapeake IRB ID: 00008891 
Number of Subjects: 6 
Number of Sites: 18 
Dates: October 2013 
1. Evaluate ability of receptacle to 
remain adhered to skin over 96-hour 
period. 
2. Evaluate skin integrity after 
receptacle was adhered for 96 hours. 
3. Identify activities that may degrade 
adhesion of receptacle to the skin. 
• ivWatch receptacles remained 
adhered to skin for 96 hours 
when combined with occlusive 
dressing. 
• The ivWatch receptacle did 
not cause significant disruption 
to skin integrity after 96 hours.  
Average Adhesion Time 
• Receptacle Only: 
   68 hrs (6 sites) 
• Receptacle & Dressing:  
    96 hrs (6 sites) 
• Receptacle, Dressing, Sensor: 
    96 hrs (6 sites) 
Device Validation for Non-
Infiltrated Tissues  
ivWatch Study ID: IVW400CS-
05 
Chesapeake IRB ID: 00009175 
Number of Subjects: 40 
Number of Sites: 40 
Dates: January 2014 
 
1. Validation trial measuring safety and 
efficacy of final Model 400 device 
when monitoring non-infiltrated 
tissues.  
2. Estimate rates of non-infiltration 
alarms for active patients in a 
hospital room environment. 
3. Demonstrate performance in the 
presence of interference sources. 
• Device can monitor normal 
tissue with minimal impact on 
clinical alarm fatigue. 
• The device can be used 
without skin irritation or 
disruption to the skin integrity. 
• The device operates properly in 
cases of interference by other 
light sources. 
Red Alarm Rate:  
• 0.24 red alarms / day 
• 1 red alarm every 4.2 days 
• 9 alarms in 900 hours 
 
Yellow-Only Alarm Rate:  
• 0.51 yellow alarms / day 
• 1 yellow alarm every 2.0 days 
19 alarms in 900 hours 
Device Validation for 
Infiltrated Tissues  
ivWatch Study ID: IVW400CS-
06 
Chesapeake IRB ID: 00009285 
Number of Subjects: 70 
Number of Sites: 140 
Dates: February 2014 
1. Validation trial measuring safety and 
efficacy of final Model 400 device 
when monitoring infiltrated tissues. 
2. Estimate sensitivities of device for 
detecting early-stage infiltrations (< 
10mL infiltrated fluid). 
3. Demonstrate significant 
improvement compared to routine 
observation by a perfect clinician. 
• Detected vast majority of 
infiltrations regardless of 
infiltration rate, PIV location, 
skin pigmentation, or body 
type. 
• Significant improvement 
compared to the current 
standard – routine observation 
by a nurse. 
• No 
safety 
concerns 
were 
observed – no skin irritation or 
disruption to skin integrity 
Red Alarm Sensitivity:  
• 96.4% Sensitivity  
• Red Alarm on 135 out of 140 
cases 
• 91.4 to 98.7% for 95% Conf. 
Interval 
 
Yellow Alarm Sensitivity:  
• 99.3% Sensitivity  
• Yellow Alarm on 139 out of 140 
cases 
95.5 to 99.96% for 95% Conf. 
Interval 
The Effect of Sensor-to-
Catheter Distance 
ivWatch Study ID:  
IVW-CLR-CS12-400 
Chesapeake IRB ID: 00010217 
Number of Subjects: 23 
Number of Sites: 46 
Dates: November 2014 
1. 
Quantify the sensitivity of the 
ivWatch device for each catheter-
to-sensor distance. 
2. 
Estimate the detected volume for 
the yellow and red notifications of 
the ivWatch device as a function 
of catheter-to-sensor distance. 
• The device detected most 
infiltrations although the 
detected volume increased for 
larger sensor-to-catheter 
separations 
• The device sensitivity decreases 
with larger separations 
consistent with the hypothesis 
that the infiltration does not 
always diffuse uniformly. 
Sensitivity: 
• 100% for 10 & 20mm separations 
• 90% for 30mm separation 
• 89% for 40mm separation 
• 78% for 50mm separation 
Detected Volume (Median): 
• 2.8, 7.7, 12.3, 21.7, 32.8 mL for  
10, 20, 30, 40, 50mm separations, 
respectively. 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
14 of 58 
Infiltration Detection when 
Placing Over the Dressing 
ivWatch Study ID:  
IVW-CLR-CS15-400 
Chesapeake IRB ID: 00013715 
Number of Subjects: 24 
Number of Sites: 48 
Dates: October 2015 
1. 
Estimate the difference in 
detected volume when placing 
above and below dressing. 
2. 
Demonstrate statistically significant 
improvement for detecting early 
stage infiltrations in comparison to 
hourly observations by a perfect 
clinician. 
• The device detected most 
infiltrations with no statistically 
significant difference in 
sensitivities for over or under the 
dressing. 
• No statistically significant 
difference between detected 
volumes for over or under the 
dressing. 
Sensitivity: 
• 100% (24/24) for under the 
dressing 
• 95.8% (23/24) for over the 
dressing 
Detected Volume (Mean): 
• 2.93 and 2.75 mL for under and 
over the dressing, respectively. 
 
Performance for Non-
Infiltrated Tissues when 
Placing Over Transparent 
Occlusive Dressing 
ivWatch Study ID:  
IVW-CLR-CS16-400 
Chesapeake IRB ID: 00015068 
Number of Subjects: 25 
Number of Sites: 25 
Dates: April-June 2016 
1. 
Estimate the non-infiltration red and 
yellow notification rates for the 
ivWatch device. 
2. 
Determine whether the over-the-
dressing red notification rate is 
significantly less than 1 false red 
notification per day. 
• Red and yellow notification 
rates occur less than once per 
day 
• Device can monitor normal 
tissue while placed over a clear 
occlusive dressing with minimal 
impact on clinical alarm 
fatigue 
• Slightly higher notification rates 
than previous motion studies 
 
Red Alarm Rate:  
• 0.44 red alarms / day 
• 1 red alarm every 2.28 days 
• 10 alarms in 548 hours 
 
Yellow-Only Alarm Rate:  
• 0.57 yellow alarms / day 
• 1 yellow alarm every 1.76 days 
• 13 alarms in 548 hours 
Optical Detection of 
Intravenous Infiltration: A 
Pilot Study 
ivWatch Study ID:  
IVW400CS-09 
CCCHMC IRB ID: 2015-0896 
Number of Subjects: 243 
Dates: August 2015 to July 
2016 
1. 
Clinical trial in a children’s hospital 
to demonstrate safety and 
efficacy in pediatric subjects. 
2. 
Time to detection – estimate 
difference in time when infiltration 
is detected by clinician and 
ivWatch. 
3. 
Device sensitivity – estimate 
ivWatch sensitivity at identifying 
infiltrations before the clinician. 
4. 
Notification Rate – estimate of the 
number of notifications per day 
without clinician-confirmed 
infiltrations. 
• The device detected and 
alerted clinicians of infiltrations 
several hours before they are 
normally found by clinician 
assessment 
• The device performance did 
not depend on the age / size 
of the subject 
Time to detection: 
• Median time difference: 15.2 
hours 
• Range: 1.3 to 99.8 hours 
Sensitivity 
• 78.3% (18/23) for Non-alarming 
group 
• 80.0% (12/15) for Alarming group 
Notification Rate 
• 0.28 red alarms / day 
• 0.27 yellow alarms / day 
 
 
 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
15 of 58 
Table 3. Clinical studies performed with SmartTouch sensor. 
Study 
Purpose 
Outcome 
Key Performance Metrics 
Monitoring Infiltrated 
Tissues  
ivWatch Study ID: IVW-CLR-
CS19-400 
Chesapeake IRB ID: 00023277 
Number of Subjects: 64 
Number of Sites: 128 
Dates: November 2018 
 
1. 
Determine if infiltration signals 
measured with the SmartTouch 
sensor are equivalent to those 
measured with the Model 400 
sensor. 
2. 
Contribute 
study 
data 
to 
a 
database of ivWatch signals of 
infiltrated tissue. 
3. 
Evaluate processing algorithms to 
optimize 
performance 
of 
the 
ivWatch 
infiltration 
detection 
algorithm. 
 
• No statistical difference in the 
performance of the 
SmartTouch sensor versus the 
Model 400 fiber optic sensor, 
when accounting for catheter 
depth and distance using a 
linear regression model. 
• Catheter depth and distance 
were significantly different than 
IVW-CLR-CS06-400, impacting 
sensitivity but not detection 
volume. 
 
Red Alarm Sensitivity  
• 91.4% Sensitivity 
• Red Alarm in 117 out of 128 
cases 
Yellow Alarm Sensitivity  
• 93.0% Sensitivity 
• Yellow Alarm in 119 out of 128 
cases 
Detected Volume (mean) 
• Red Alarm: 3.7mL 
• Yellow Alarm: 3.3mL 
Signal Variation of Normal 
Tissue  
ivWatch Study ID: IVW-CLR-
CS20-400CS 
Chesapeake IRB ID: 00023891 
Number of Subjects: 30 
Number of Sites: 30 
Dates: December-January 
2018 
1. 
Quantify the signal variation of 
normal tissue in a setting that 
approximates the hospital room 
environment. 
This 
includes 
calculating distribution metrics such 
as mean and standard deviation 
for the collected signals. 
2. 
Evaluate processing algorithms to 
optimize 
performance 
of 
the 
ivWatch device with SmartTouch 
sensor. 
3. Determine if non-infiltration red-
notification and yellow-notification 
rates 
are 
equivalent 
to 
those 
recorded with the Model 400 
sensor. 
• The SmartTouch sensor has a 
similar false-notification 
performance to the Model 400 
fiber optic sensor.  
• Both red and yellow estimated 
notification rates are within the 
95% confidence intervals 
reported in “ivWatch Model 
400: Device Validation for Non-
Infiltrated Tissues”. 
Red Alarm Rate:  
• 0.312 red alarms / day 
• 95% confidence interval 0.133 to 
0.733 red alarms / day 
Yellow Alarm Rate:  
• 0.486 red alarms / day 
• 95% confidence interval: 0.176 to 
1.139 yellow alarms / day 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
16 of 58 
Device Verification for 
Infiltrated Tissues  
ivWatch Study ID: IVW-CLR-
CS22-400 
Chesapeake IRB ID: 00030567 
Number of Subjects: 128 
Number of Sites: 256 
Dates: December 2018 
 
1. 
Determine if infiltration sensitivity 
measured with the SmartTouch 
sensor is equivalent to the Model 
400 fiber optic sensor. 
2. 
Contribute 
study 
data 
to 
a 
database of ivWatch signals of 
infiltrated tissue. 
3. 
Evaluate processing algorithms to 
optimize 
performance 
of 
the 
ivWatch device with SmartTouch 
sensor. 
Subject enrollment is complete. 
The data analysis is in progress. 
Analysis in progress 
Device Verification for Non-
Infiltrated Tissues  
ivWatch Study ID: IVW-CLR-
CS23-400 
Chesapeake IRB ID: 00030569 
Number of Subjects: 30 
Number of Sites: 60 
Dates: December 2018 – 
January 2019 
 
1. 
Quantify the non-infiltration red-
alarm and yellow-alarm rates for 
the SmartTouch sensor. 
2. 
Determine if non-infiltration red-
notification and yellow-notification 
rates of the SmartTouch sensor are 
equivalent to the Model 400 fiber 
optic sensor. 
3. 
Evaluate 
signal 
processing 
algorithms to optimize performance 
of 
the 
ivWatch 
device 
with 
SmartTouch sensor. 
 
Subject enrollment is complete. 
The data analysis is in progress. 
Analysis in progress 
Device Verification for Non-
Infiltrated Tissues, Part II 
ivWatch Study ID: IVW-CLR-
CS26-400 
Chesapeake IRB ID: 00032326 
Number of Subjects: 15 
Number of Sites: 30 
Dates: February – March 2019 
1. 
Quantify the non-infiltration red-
notification and yellow-notification 
rates for the SmartTouch sensor. 
2. 
Evaluate processing algorithms to 
optimize 
performance 
of 
the 
ivWatch 
device 
with 
the 
SmartTouch sensor. 
3. Determine if non-infiltration red-
notification and yellow-notification 
rates are equivalent to those 
recorded with the Model 400 
sensor. 
Enrollment is open, 11/15 
accepted case studies 
complete to date.  
Analysis in progress 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
17 of 58 
The Effect of PIV Depth and 
Site 
ivWatch Study ID: IVW-CLR-
CS25-400 
Chesapeake IRB ID: 00032269 
Number of Subjects: 64 
Number of Sites: 128 
Dates: March 2019 
1. 
Determine whether the catheter 
depth has a significant effect on 
the measured infiltration signal.  
2. 
Determine whether the catheter 
site has a significant effect on the 
measured infiltration signal.  
3. 
Contribute study data to a 
database of ivWatch signals of 
infiltrated tissue.  
4. 
Evaluate processing algorithms to 
optimize performance of future 
ivWatch devices.  
Subject enrollment is finished for 
this study. The data analysis is in 
progress. 
Analysis in progress 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
18 of 58 
Study Goals and Objectives 
The goal of this study is to validate the performance of the ivWatch SmartTouch sensor for 
detecting the early stages of an IV infiltration, as collected from healthy adult volunteers. The 
Model 400 Fiber Optic sensor is used for performance comparison. The study objectives include: 
Primary Objective: Demonstrate a statistically significant improvement for detecting early stage 
infiltrations in comparison to hourly observation by a perfect clinician. 
Secondary Objectives: 
1. Demonstrate statistical equivalence in infiltration detection volume of the SmartTouch and 
Fiber Optic sensors. 
2. Demonstrate statistical equivalence in infiltration sensitivity of the SmartTouch and Fiber 
Optic sensors. 
Study Design 
Approximately 115 subjects may be enrolled in the study with the goal of achieving 98 accepted 
case studies. The study coordinator will attempt to enroll at least 20 subjects (20%) with dark skin 
pigmentation and at least 20 subjects (20%) who are classified as obese by their body mass index 
(BMI), but these are not required enrollment criteria as skin pigmentation and BMI have proven to 
be insignificant variables in previous ivWatch studies. The intent is to include subjects with different 
skin pigmentations and body types such that the study represents the intended population of the 
device. The duration of each study depends on the randomly selected infiltration rates. A study 
may take up to 2 hours to complete. This corresponds to the subjects receiving the 5mL/hr 
infiltration rate.  
Medical professionals will be used for the health screening of the subject and placement of the 
catheters. If the research subject is deemed acceptable for the study, various metrics of each 
subject will be measured, as summarized in Figure 4. These measurements include the weight, 
height, blood pressure, forearm circumference, skin tone (light, medium, or dark), and skin 
classification. The skin classification is performed by using the subject pigmentation worksheet to 
determine the subject’s Fitzpatrick skin type. The subject’s body mass index is calculated from the 
weight and height measurements and is used as a measure of the subject’s body type 
(underweight, normal, overweight, obese). These metrics are recorded for post-study analysis to 
identify correlations between the measured signal and anatomical/physiological characteristics 
of the research subjects. 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
19 of 58 
 
Figure 4. Pre-study measurements performed on each subject. 
After completing the informed consent and health history forms, the subject is taken to the test 
room, which is designed to approximate an infusion center. The room also includes two IV pumps 
and two ivWatch patient monitors per subject. The study configurations have been randomized 
and are included in Table 4.  
During the study, each subject will receive two subcutaneous injections of isotonic saline solution. 
These injections will be randomly selected from the four possible locations shown in Figure 5. These 
four locations represent the most common injection sites for PIV therapy. The subcutaneous 
injections closely approximate the conditions of a PIV infiltration without exposing the research 
subject to additional risks and discomforts associated with puncturing a vein (e.g. ecchymosis, 
hematoma, phlebitis, thrombosis, embolism). The subcutaneous injections will be performed using 
the same equipment as a PIV procedure.   
 
Figure 5. The four possible anatomical sites monitored during this study. 
 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
20 of 58 
Table 4. The study configuration. 
CRF 
Site 
Rate 
Fiber Optic 
Side 
SmartTouch 
Side 
  
CRF 
Site 
Rate 
Fiber Optic 
Side 
SmartTouch 
Side 
1 
Forearm 
50 
Left 
Right 
  
50 
Forearm 
25 
Left 
Right 
2 
Hand 
5 
Right 
Left 
  
51 
Hand 
25 
Right 
Left 
3 
Forearm 
5 
Left 
Right 
  
52 
Hand 
50 
Left 
Right 
4 
Forearm 
100 
Left 
Right 
  
53 
Hand 
75 
Right 
Left 
5 
Hand 
75 
Left 
Right 
  
54 
Forearm 
125 
Left 
Right 
6 
Forearm 
150 
Left 
Right 
  
55 
Hand 
100 
Left 
Right 
7 
Hand 
125 
Left 
Right 
  
56 
Forearm 
75 
Left 
Right 
8 
Hand 
150 
Right 
Left 
  
57 
Hand 
75 
Left 
Right 
9 
Hand 
100 
Right 
Left 
  
58 
Hand 
5 
Right 
Left 
10 
Forearm 
100 
Right 
Left 
  
59 
Forearm 
150 
Left 
Right 
11 
Hand 
50 
Right 
Left 
  
60 
Forearm 
25 
Right 
Left 
12 
Forearm 
150 
Right 
Left 
  
61 
Forearm 
75 
Right 
Left 
13 
Forearm 
50 
Right 
Left 
  
62 
Hand 
150 
Right 
Left 
14 
Hand 
100 
Left 
Right 
  
63 
Hand 
75 
Right 
Left 
15 
Hand 
100 
Right 
Left 
  
64 
Forearm 
100 
Left 
Right 
16 
Hand 
5 
Left 
Right 
  
65 
Hand 
100 
Right 
Left 
17 
Forearm 
5 
Right 
Left 
  
66 
Hand 
125 
Left 
Right 
18 
Forearm 
100 
Left 
Right 
  
67 
Hand 
25 
Left 
Right 
19 
Hand 
5 
Right 
Left 
  
68 
Forearm 
25 
Left 
Right 
20 
Forearm 
5 
Left 
Right 
  
69 
Forearm 
5 
Left 
Right 
21 
Forearm 
125 
Right 
Left 
  
70 
Forearm 
100 
Right 
Left 
22 
Hand 
50 
Left 
Right 
  
71 
Forearm 
50 
Left 
Right 
23 
Forearm 
50 
Left 
Right 
  
72 
Hand 
50 
Right 
Left 
24 
Hand 
150 
Left 
Right 
  
73 
Hand 
100 
Left 
Right 
25 
Hand 
125 
Right 
Left 
  
74 
Forearm 
75 
Left 
Right 
26 
Forearm 
125 
Left 
Right 
  
75 
Forearm 
50 
Right 
Left 
27 
Forearm 
75 
Right 
Left 
  
76 
Hand 
50 
Left 
Right 
28 
Forearm 
150 
Left 
Right 
  
77 
Forearm 
150 
Right 
Left 
29 
Hand 
125 
Left 
Right 
  
78 
Forearm 
50 
Left 
Right 
30 
Forearm 
25 
Right 
Left 
  
79 
Hand 
150 
Left 
Right 
31 
Hand 
75 
Right 
Left 
  
80 
Forearm 
150 
Left 
Right 
32 
Hand 
25 
Left 
Right 
  
81 
Forearm 
125 
Right 
Left 
33 
Forearm 
25 
Left 
Right 
  
82 
Hand 
75 
Left 
Right 
34 
Forearm 
125 
Right 
Left 
  
83 
Hand 
5 
Left 
Right 
35 
Hand 
50 
Right 
Left 
  
84 
Forearm 
5 
Right 
Left 
36 
Hand 
5 
Left 
Right 
  
85 
Hand 
25 
Right 
Left 
37 
Hand 
125 
Right 
Left 
  
86 
Hand 
5 
Right 
Left 
38 
Forearm 
5 
Right 
Left 
  
87 
Hand 
50 
Right 
Left 
39 
Forearm 
50 
Right 
Left 
  
88 
Hand 
125 
Right 
Left 
40 
Hand 
150 
Right 
Left 
  
89 
Hand 
150 
Right 
Left 
41 
Forearm 
100 
Right 
Left 
  
90 
Hand 
25 
Left 
Right 
42 
Forearm 
150 
Right 
Left 
  
91 
Forearm 
75 
Right 
Left 
43 
Hand 
25 
Right 
Left 
  
92 
Forearm 
125 
Left 
Right 
44 
Forearm 
25 
Right 
Left 
  
93 
Forearm 
100 
Left 
Right 
45 
Forearm 
75 
Left 
Right 
  
94 
Hand 
125 
Left 
Right 
46 
Hand 
25 
Left 
Right 
  
95 
Forearm 
5 
Left 
Right 
47 
Hand 
75 
Left 
Right 
  
96 
Hand 
100 
Right 
Left 
48 
Hand 
150 
Left 
Right 
  
97 
Forearm 
125 
Right 
Left 
49 
Forearm 
75 
Right 
Left 
  
98 
Forearm 
25 
Right 
Left 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
21 of 58 
All subcutaneous injections in this research protocol are infiltrated between 5mL/hr and 150mL/hr, 
as listed in Table 4. Each injection is limited to a total of 10 mL of saline solution to minimize subject 
discomfort. This 10mL volume limit corresponds to a 2 hour infiltration at the 5mL/hr IV pump rate 
and a 4 minute infiltration at the 150mL/hr IV pump rate. 
The nurse will examine each site before placing the IV catheters. Photographs of the illumination 
by a NIR vein viewer will be captured as a record of the subject’s vascular structure at the site. 
The nurse will place the IV catheters at approximately the same anatomical location on each 
arm. The catheter depth will be monitored and recorded using the SonoSite S-Series ultrasound 
imaging system, shown in Figure 6. The nurse places the catheter immediately adjacent to a vein 
typically used for IV therapy. Placing the catheter tip close to the vein wall ensures the saline 
diffuses similar to a real-world infiltration. 
 
Figure 6. The Sonosite S-Series commercial ultrasound imaging system. 
After placement of the catheter, each subject will receive the SmartTouch sensor on one side and 
the Model 400 fiber optic sensor on the other side according to the random study configuration. 
The sensor is placed next to the injection site. An example of the ivWatch SmartTouch sensor is 
shown in Figure 7. The nurse will dress the site using standard hospital procedures and occlusive 
dressings. Photographs will be captured to record the position of the sensor with respect to the 
catheter. The sensor cable will be taped to the IV tubing and routed to the IV pole. The IV tubing 
/ ivWatch sensor cable bundle will be secured to the subject using medical tape following 
standard hospital procedures. 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
22 of 58 
 
Figure 7. Example of the ivWatch SmartTouch sensor 
 
The sensor is connected to the IPM. A rendering of the patient monitor is included in Figure 8. The 
rendering identifies the user interface elements on the front face of the IPM. The IPM is attached 
to the IV pole. The IPM records data during the study and is attached to the IV pole. 
Once the ivWatch sensors have been placed on the subject, data acquisition will be started on 
the two ivWatch patient monitors. This represents time zero (t = 0) in the study. Study staff will record 
the timing of study events (starting and stopping IPMs, starting and stopping pumps) using a digital 
wall clock. The pumps will be turned on after 5 minutes of monitoring. The IV pumps will stop after 
10mL of isotonic saline solution has been injected into the tissue. Once the pumps have been 
stopped for both sites, the IPMs will collect data for an additional 5 minutes. 
Once the data acquisition is complete, the research assistant captures photographs of the two 
sites to record the visual appearance of the region. The ivWatch components are removed from 
the sites. An ultrasound technician will then capture ultrasound images of the sites to record 
structure of the infiltrated tissue under the sensor and measure catheter depth. The IV’s are then 
removed from the research subject. A final photograph is captured of the bare sites. The 
photographs are intended to record the skin integrity, such as whether the research subject had 
an allergic reaction to any materials or if the skin was damaged when removing adhesive-backed 
sensors. 
ivWatch, LLC believes this study design provides the signal characteristics that are representative 
of those expected in a clinical setting. This data will enable the researchers to understand 
differences, if any, between the optical signal characteristics of infiltrated tissue data collected 
with the SmartTouch sensor versus the Model 400 sensor. 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
23 of 58 
 
Figure 8. The ivWatch Patient Monitor with extension module and user interface elements. 
Methodology 
Subject Recruitment 
Previous research participants of ivWatch clinical studies will be recruited to participate in the 
study. Advertisements are not needed to obtain the number of accepted case studies. The study 
will be limited to healthy adult volunteers (18 years or older). During the initial recruitment, 
interested participants will be provided an overview of the study and an initial pre-screen will be 
completed. If eligibility is unclear during the pre-screening process, the registered nurse can 
consult the chief nursing officer or investigator to determine eligibility. The pre-screening form is 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
24 of 58 
included on page 42. If the participant is interested in the study, 18 years or older, and deemed 
an acceptable research subject, a time and date for the study will be scheduled with the subject. 
The formal consent and screening process will be performed on the day of the study, as described 
in the following section. 
Preliminary Information and Consent 
The pre-study procedure is listed in detail on page 46. Once arriving at the study site, the subject 
fills out a sign-in sheet indicating their name and the time of their arrival. The subject is then taken 
to a private screening room. A research assistant will welcome the subject and provide the 
informed consent document. The research assistant will discuss the main points of the study and 
the subject’s rights, as described in the consent form. 
If the subject understands and signs the consent form, the subject will be asked to fill out a 
participant health history form. The purpose of the health history form is to prevent potentially sick 
or unhealthy subjects from participating in the trial. Each subject must complete the health and 
consent forms before participating in the study. As part of the health history form, the nurse will 
measure the body temperature of the subject with the goal of preventing sick individuals from 
participating in the study.  
The nurse reviews the subject’s health report form to determine if the subject qualifies for the study. 
A list of exclusion criteria is included in Table 5. Any additional concerns or questions will be 
directed to the on-staff chief nursing officer and/or medical doctor. They may use their 
professional judgment to exclude a subject for reasons not included in this list of exclusion criteria. 
Table 5. List of study exclusion criteria. 
1 
Abnormal bleeding / hemophilia 
2 
Absence of sensation in arms 
3 
Anemia 
4 
Cardiopulmonary disorders 
5 
Clotting disorders 
6 
Currently pregnant 
7 
Dehydration 
8 
Dizziness or fainting 
9 
Hepatitis 
10 
HIV / Aids 
11 
Immune Deficiency Disorders 
12 
Lymphedema 
13 
Major surgery or scar tissue which would complicate PIV access 
14 
Radiation / chemotherapy within last year 
15 
Received IV therapy in last 14 days 
16 
Seizures 
17 
Stroke 
18 
Sick or had infection in past 14 days 
19 
High Temperature (>99.6°F) 
20 
Blood thinning medication (e.g. aspirin regimen, Coumadin, warfarin) 
21 
Tattoos covering more than half of back of hand or inner forearm 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
25 of 58 
If the subject completes the informed consent document and the health history report form is 
approved, then the first three sections of the case report form should be completed, which 
includes general study information, inclusion criteria, and subject information. An example of the 
case report form is included in the Case Report Form section of this research protocol. 
Several metrics of the subject’s body are measured as a record of the body type and physiology. 
These metrics include body weight, height, blood pressure, and circumference of the forearm. 
The body metrics are recorded in Section 4 of the case report form. The research assistant will also 
work with the subject to complete a subject pigmentation worksheet. The results of this worksheet 
are recorded in Section 5 of the case report form. 
The selected study configuration information (Table 5) is recorded in Section 6 of the case report 
form and the serial numbers of the ivWatch patient monitors, extension module, sensor cables, 
and receptacle are recorded in Section 7 of the case report form. 
Data Collection 
The data collection checklist is included on page 47. The data collection consists of three 
processes: (1) subject preparation, (2) data collection, and (3) study completion. 
Subject Preparation 
Once the preliminary information is collected, the subject will be taken to the test area. The nurse 
and ultrasound tech will perform hand hygiene and put on latex-free medical-grade gloves. Each 
subject has two injection sites. The sites are prepared using the same procedure, except one site 
will use the SmartTouch sensor and one site will use the fiber optic sensor. The nurse and research 
assistant will examine the potential sites. A photograph of the VeinViewer illumination will be 
captured as a record of the vascular structure at the site. A second photograph will be captured 
of the bare site where the injection will occur. This photograph will be compared to a post-study 
photograph to see if there is any skin irritation associated with the ivWatch sensor. The filenames 
of these photographs are recorded in Section 7 of the case report form. 
Using protocols based on hospital procedures, the nurse cleans the site with a CHG swabstick for 
30 seconds and allows to air dry for 30 seconds. The nurse inserts the catheter next to a vein that 
would typically be used for a PIV therapy. Once the insertion is complete, a shallow high-resolution 
ultrasound image of the catheter and surrounding tissue is captured. The image should show as 
much of the catheter length as possible, while also including the catheter tip. The depth of the 
catheter tip relative to the skin surface is measured and the corresponding image is saved. The 
ultrasound image File ID and the measured depth are recorded in the case report form. 
The nurse places the ivWatch sensor within 5 mm of the approximate location of the catheter tip. 
After sensor and occlusive dressing placement, the sensor cable and IV tubing are secured to the 
subject’s arm using medical tape. 
Once complete, the research assistant will capture a photograph of the dressed site. This 
photograph can be used to measure the separation between the catheter tip and the ivWatch 
sensor in a post study analysis. The nurse will measure the circumference of each site. The 
photograph file ID and circumference are recorded in the case report form. 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
26 of 58 
Data Collection 
After both sites have been set up, the nurse will start the data acquisition on the ivWatch patient 
monitors (t=0). A digital clock is used to record the ivWatch acquisition and infiltration start times. 
The acquisition start times are recorded in the case report form. The IPMs collect data for 5 minutes. 
After the normal acquisition period is complete, the IV pumps are started at their specified rate 
(either 5, 25, 50, 75, 100, 125, or 150 mL/hr). The pumps will stop automatically after a total of 10mL 
of isotonic saline is pumped into the subcutaneous tissue. The stop times will be recorded in the 
case report form. The data acquisition will be stopped on the two IPMs five minutes after the slower 
of the two infiltrations is complete. The research assistant will record the times of these actions in 
Section 8 of the case report form. 
 
End of Study 
Once the ivWatch data acquisition is complete, additional data is recorded from both sites. First, 
a post study circumference measurement of the site is performed by the nurse and recorded in 
the case report form. Then, a photograph is captured of the injection site as a record of the visual 
swelling. The file identification information of this photograph is recorded in the case report form.  
The occlusive dressing and ivWatch sensor are carefully removed from the injection site without 
pulling out the catheter. The research assistant captures a photograph of the VeinViewer 
illumination and records the photo ID in the case report form. A series of ultrasound images are 
captured to record the state of the tissue under the sensor. The file identification information for 
the ultrasound image is recorded in the case report form. Once the ultrasound imaging is 
complete, the catheter is removed. Light pressure is applied if there is any bleeding (usually there 
is no bleeding since this is a subcutaneous injection). A final photograph is captured of the site as 
a record of skin integrity and whether the ivWatch sensor caused any irritation to the skin. An 
adhesive bandage is applied to the site. 
Once this procedure has been completed for both sites, the research assistant completes the 
remaining sections of the case report form, which include areas for adding miscellaneous notes, 
a description of any device deficiencies/malfunctions that occurred, a description of any adverse 
events that occurred, and an area for an investigator to authorize the case report form. Once the 
case report form is complete, the subject is taken to the front reception desk and given the 
participation payment. The subject is asked to sign and date a check-out sheet to verify receipt 
of payment. A copy of their informed consent form with contact information will be given to the 
subject should they have any questions or concerns after departing ivWatch. 
The research assistant is responsible for cleaning and re-organizing the test area after the subject 
has departed. This includes removing tape connecting the IV tubing to the ivWatch sensor, 
disposing the used IV tubing, and cleaning the ivWatch sensor and monitor with hospital-grade 
disinfectant wipes. Data saved during the study will be removed from the corresponding 
machines and saved to a secure network server. The data includes IPM data (transferred via USB 
drive), ultrasound images (transferred via USB drive), and camera images. 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
27 of 58 
The research assistant will store all paperwork from the study (case report forms, subject 
pigmentation forms) in a manila folder in a secure location. All paperwork containing private 
health information is given to the HIPAA officer or designee for separate and secure storage. 
Data Analysis 
After the study is complete, a series of analyses will be performed on the collected ivWatch data. 
Specific statistical tests and rationale are included in the Statistical Considerations section of this 
protocol (page 31).  
Possible reasons a study may be rejected include, but are not limited to: 
1. Equipment (infusion pump, catheter, patient monitor) not operating properly. 
2. Leaking catheter or IV site. 
3. Early termination by research subject. 
4. Sensor placement more than 2 cm from the catheter tip. 
5. Significant deviations from research protocol. 
All data analyses will be independently reviewed and verified by a second researcher. 
Risk Benefit Analysis 
Injection of Isotonic Saline 
The study design is considered to have minimal risk to the healthy adult volunteers participating in 
this study. Previous studies have generated infiltrations by intentionally pushing the needle through 
the vein wall into the surrounding subcutaneous tissue. The placement of the needle into the vein 
introduces additional risks such as ecchymosis, hematoma, phlebitis, thrombosis, and embolism. 
This study generates an infiltration by performing subcutaneous injections of isotonic saline solution. 
This method of generating infiltrations is believed to be much safer for the research subject, 
including being less painful than puncturing a vein wall. 
The most likely complication associated with subcutaneous injections would be an infection. The 
risk of an infection is reduced by (1) only enrolling healthy adult volunteers (that is, subjects are 
not immunocompromised) and (2) using safe procedures based on standard hospital practices 
(PIV therapy) and medical-grade sterile materials (e.g. ultrasound gel, occlusive dressing). 
Another complication could include hitting a nerve causing significant pain for the subject. This 
risk is minimized by using an experienced nurse to perform the injections at common sites for PIV 
therapy. 
A registered nurse or physician with significant PIV therapy experience will perform all of the 
injections and will be onsite throughout the study. ivWatch, LLC has two medical doctors available 
by phone should any medical related questions arise during a study. 
Infusion of saline solution into the subcutaneous tissue does not pose a significant risk to the study 
subjects. Hypodermoclysis is a common medical practice of injecting saline into subcutaneous 
tissues for treatment or prevention of dehydration. This is typically used for elderly patients. 
Hypodermoclysis is performed on a variety of sites including back, abdomen, and upper regions 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
28 of 58 
of the arms and legs. Pump rates range from 20 to 125mL/hr with a total delivered volume less 
than 1500mL in a 24 hour period [10]. In comparison to the hypodermoclysis procedure, the study’s 
10mL maximum volume and 5 to 150 mL/hr flow rates of 0.9% saline do not pose a significant 
health risk to the study subjects.  
The ivWatch Technology 
The ivWatch technology is a non-significant risk device as determined by the FDA. In a face-to-
face meeting with the FDA on March 28, 2014, the FDA classified the ivWatch Model 400 as a Class 
II, NSR device. The ivWatch Model 400 has received marketing clearance from the FDA for adults 
and pediatrics. Early prototypes of the Model 400 were evaluated in previous clinical studies with 
IRB approval. A list of these studies is included in Table 6. 
The electronic sensor is designed to perform identically to the Model 400 fiber optic sensor. The 
materials used for the electronic sensor are common medical grade materials and are generally 
regarded as safe. The amount of LED light emitted by the sensor into the patient’s skin is 
significantly less than the maximum permissible ocular and skin exposures published in the ANSI 
Z136.1 Laser safety standard. To our knowledge, there is no standard regulating the safety of LED 
emitting products, so the laser safety standard has been used to demonstrate the safety of the 
emitted optical powers. The amount of heat generated by the LEDs in the sensor head is much 
lower than conventional pulse oximeters, due to a low duty cycle and optical power, as well as 
an optimized photodiode amplification circuit. 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
29 of 58 
Table 6. Clinical trials involving the ivWatch technology. 
STUDY 
SPONSOR 
INVESTIGATOR 
IRB NO. 
Healthy adult volunteer study & 
nurse focus group 
CW Optics 
University of Virginia 
Medical Center 
HIC11383 
Adult patient study 
CW Optics 
Virginia Commonwealth 
University Medical Center 
HM12146 
Pediatric Study 
ivWatch, LLC 
Cincinnati Children’s 
Hospital Medical Center 
2009-2550 
NIR Detection of PIV Infiltration 
ivWatch, LLC 
ivWatch, LLC 
Chesapeake IRB 
ID: 00008513 
The Signal Variation of Normal 
Tissue 
ivWatch, LLC 
ivWatch, LLC 
Chesapeake IRB 
ID: 00008218 
The Effect of Catheter Depth 
ivWatch, LLC 
ivWatch, LLC 
Chesapeake IRB 
ID: 00008254 
The Effect of Infiltration Rate 
ivWatch, LLC 
ivWatch, LLC 
Chesapeake IRB 
ID: 00008941 
Long Term Adhesion of the 
ivWatch Receptacle 
ivWatch, LLC 
ivWatch, LLC 
Chesapeake IRB 
ID: 00008891 
Device Validation for Non-
Infiltrated Tissues 
ivWatch, LLC 
ivWatch, LLC 
Chesapeake IRB 
ID: 00009175 
Device Validation for Infiltrated 
Tissues 
ivWatch, LLC 
ivWatch, LLC 
Chesapeake IRB 
ID: 00009285 
The Effect of Sensor-to-Catheter 
Distance 
ivWatch, LLC 
ivWatch, LLC 
Chesapeake IRB 
ID: 
00010217 
Infiltration Detection when 
Placing Over the Dressing 
ivWatch, LLC 
ivWatch, LLC 
Chesapeake IRB 
ID: 00013715 
Performance for Non-Infiltrated 
Tissues when Placing Over 
Transparent Occlusive Dressing 
ivWatch, LLC 
ivWatch, LLC 
Chesapeake IRB 
ID: 00015068 
Optical Detection of Intravenous 
Infiltration: A Pilot Study 
ivWatch, LLC 
Cincinnati Children’s 
Hospital Medical Center 
2015-0896 
 
ivWatch SmartTouch Sensor: 
Monitoring Infiltrated Tissues 
ivWatch, LLC 
ivWatch, LLC 
Chesapeake IRB 
ID: 00023891 
ivWatch SmartTouch Sensor: 
Signal Variation of Normal Tissue 
ivWatch, LLC 
ivWatch, LLC 
Chesapeake IRB 
ID: 00023277 
ivWatch SmartTouch Sensor: 
Device Verification for Infiltrated 
Tissues 
ivWatch, LLC 
ivWatch, LLC 
Chesapeake IRB 
ID: 00030567 
ivWatch SmartTouch Sensor: 
Device Verification for Non-
Infiltrated Tissues 
ivWatch, LLC 
ivWatch, LLC 
Chesapeake IRB 
ID: 00030569 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
30 of 58 
ivWatch SmartTouch Sensor: 
Device Verification for Non-
Infiltrated Tissues, Part II 
ivWatch, LLC 
ivWatch, LLC 
Chesapeake IRB 
ID: 00032326 
ivWatch SmartTouch Sensor: The 
Effect of PIV Depth and Site 
ivWatch, LLC 
ivWatch, LLC 
Chesapeake IRB 
ID: 00032269 
 
Follow-Up 
There is no anticipated need for a follow-up protocol after this study. Prior to departure, the 
research personnel will provide the subject with contact information should they have any 
questions or concerns after leaving the study. 
Data Management and Statistical Considerations 
Data Management 
The data management process includes recording data during the study, transferring data to a 
secure electronic database, and data validation. 
Five forms of data are recorded during each study: 
1. Information on the health of the study subject is recorded in the health history form. This 
form is provided in the Participant Health History Form section of this document. This form 
is completed by the subject prior to the study. The form requests only information relevant 
to the study. The health history form is stored in a locked filing cabinet at the ivWatch 
facility. 
2. Study-related information is recorded using the study’s case report form (including the 
subject activity log). The case report form includes study information (gender, age, body 
measurements, skin classification, product serial numbers, times, and filenames).  
This form is completed by the research assistant during the study. The case report form 
does not include any personal identifiers. The original forms are stored at the ivWatch 
facility. 
3. The ivWatch data is recorded using the investigational device that store the data 
internally. The filename does not contain any personal identifiers. 
4. The ultrasound images are saved to the ultrasound machine during the study. The 
filename does not contain any personal identifiers. 
5. Digital photographs and video images are recorded throughout the study. The filenames 
do not contain personal identifiers although the subjects may be identifiable in the 
images. The informed consent form discloses the collection of photographic images and 
video recordings. 
Once a study is complete, the case report form data, the ivWatch data, ultrasound images, and 
camera images are transferred to an electronic database. The ultrasound and photographic 
images are deleted from the ultrasound machine and digital camera, respectively. The database 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
31 of 58 
has been designed such that no personal identifiers are available to match a study dataset with 
a particular subject. To protect the confidentiality and integrity of the data, the password-
protected database can only be accessed by authorized users. The privileges of each authorized 
user are set by the database administrator. All changes made to the database are recorded in 
an audit log. The log includes (but is not limited to) which fields were changed and which user 
made the changes. This audit trail is necessary for data integrity as well as meeting regulatory 
guidelines. Double data entry by two people is used to verify that data is correctly entered into 
the database. After validation is complete, the database will be available to the authorized users. 
Statistical Considerations 
The goal of this study is to validate the performance of the ivWatch SmartTouch sensor for 
detecting the early stages of an IV infiltration, as collected from healthy adult volunteers. The 
Model 400 Fiber Optic sensor is used for performance comparison. The study objectives include: 
Primary Objective: Demonstrate a statistically significant improvement for detecting early stage 
infiltrations in comparison to hourly observation by a perfect clinician. 
Secondary Objectives: 
1. Demonstrate statistical equivalence in infiltration detection volume of the SmartTouch and 
Fiber Optic sensors. 
2. Demonstrate statistical equivalence in infiltration sensitivity of the SmartTouch and Fiber 
Optic sensors. 
Primary Objective 
The primary objective is to demonstrate a statistically significant improvement in the sensitivity for 
early stage infiltrations compared to the current nursing standard of care, where the performance 
of the current nursing standard is estimated using the concept of a perfect clinician. The perfect 
clinician assesses the IV site hourly and perfectly classifies the tissue as normal or infiltrated 
regardless of the volume of fluid that has been infiltrated.  The performance of the perfect clinician 
can be theoretically calculated. For the study configuration listed in Table 7, the perfect clinician 
would capture 28.2% of the infiltrations prior to an infiltrated volume of 10mL. 
Table 7. The study configuration for the infiltration study 
Rate 
(mL/hr) 
Number of 
Subjects 
Perfect 
Clinician 
Sensitivity (%) 
Number of Early Infiltrations 
Detected by Perfect 
Clinician 
5 
14 
100.0 
14.0 
25 
14 
40.0 
5.6 
50 
14 
20.0 
2.8 
75 
14 
13.3 
1.9 
100 
14 
10.0 
1.4 
125 
14 
8.0 
1.1 
150 
14 
6.7 
0.9 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
32 of 58 
A Monte Carlo simulation was performed to evaluate the hypothesis test comparing the perfect 
clinician (H0) and a device with a sensitivity of 90% (H1). The 90% sensitivity is a conservative 
assumption based on sensitivities measured in previous ivWatch studies. A total of one million trials 
were simulated using the study configuration shown in Table 7.  The infiltration detection times for 
the perfect clinician were uniformly distributed between 0 and 60 minutes. The perfect clinician 
provided early detection of an infiltration if the detection time was less than the time required to 
infiltrate 10mL at the given rate. The simulation code is included in the Statistical Monte Carlo 
Analysis Appendix (page 56). Figure 9 shows the results of the Monte Carlo analysis. A threshold of 
35% corresponded to an alpha of 0.041 (0.05 was not possible due to the discrete nature of the 
sampled sensitivities), that is, 95.9% of the null hypothesis trials (perfect clinician) had sensitivities 
less than 35%.  
 
Figure 9. The Monte Carlo simulation of a device operating with an infiltration sensitivity 
equivalent to the perfect clinician (null hypothesis) and a device operating at a 90% sensitivity 
(alternative hypothesis). The red line shows the location of α=0.041 threshold (one-sided). 
Figure 10 shows the statistical power analysis for this Monte Carlo simulation. A statistical power 
exceeding 90% was calculated for ivWatch device sensitivities greater than 42%. For the specific 
alternative hypothesis of 90% sensitivity, the statistical power was estimated to be essentially 100%. 
A sample size of 98 is assumed in this simulation, which is based on the detection volume 
comparison objective. In addition to the large statistical power, a sample size of 98 also provides 
a reasonable confidence interval on our estimated sensitivity. For a sensitivity of 91% (89/98), the 
95% confidence interval would be 0.83 to 0.96.  

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
33 of 58 
 
 
Figure 10. The statistical power for a 98 PIV site study as a function of the device sensitivity 
(specific alternative hypothesis). 
The hypothesis test for a binomial distribution will be performed following the study to ensure the 
measured sensitivities of both sensors are significantly greater (alpha = 0.05) than the perfect 
clinician. 
Secondary Objectives 
Detection Volume Comparison 
The first secondary objective is to demonstrate equivalent detection volume between the 
SmartTouch (ST) and Fiber Optic (FO) sensor. In the clinical study ivWatch Model 400: Validation 
for Infiltrated Tissues (FO sensor), where the same infusion rate configuration from Table 7 was 
implemented, the mean and standard deviation detection volume was found to be in 3.75 mL 
±2.13 mL. In order to test if the mean detection volume for the ST sensor (μST) is less than or equal 
to  the mean detection volume of the FO sensor (μFO) with a margin of error (Δ0), the following 
single-sided hypothesis test configuration is used: 
Null Hypothesis (H0): μFO- μST = Δ0 
Alternative Hypothesis (H1): μFO- μST > Δ0 
The sample size (n) needed to show equivalence is defined by the following equation: 
𝑛𝑛= (𝑧𝑧𝛼𝛼+ 𝑧𝑧𝛽𝛽)2(𝜎𝜎𝐹𝐹𝐹𝐹
2 + 𝜎𝜎𝑆𝑆𝑆𝑆
2 )
(∆−∆0)2
 
where Δ is the difference in means (μFO - μST), and σ the standard deviation of each sensor. The 
σST is estimated to be equal to σFO. The margin of error (Δ0) is assumed to be 1.0 mL, which is less 
than half of the standard deviation. An analysis of statistical power versus sample size is shown in 
Figure 11, (alpha = 0.05). A sample size of 98 subjects will provide a statistical power of 95%. Sample 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
34 of 58 
size for this clinical study is based on this objective. Following the study a single-sided student’s t-
test will be used to compare the sensor detection volumes. 
 
Figure 11. Statistical power vs sample size for detection volume comparison 
Sensitivity Comparison 
Approximate confidence intervals for the difference in sensor sensitivities (pFO – pST) will be found 
using the following equation: 
𝑝𝑝𝐹𝐹𝐹𝐹−𝑝𝑝𝑆𝑆𝑆𝑆−𝑧𝑧𝛼𝛼ඨ𝑝𝑝𝐹𝐹𝐹𝐹(1 −𝑝𝑝𝐹𝐹𝐹𝐹)
𝑛𝑛𝐹𝐹𝐹𝐹
+ 𝑝𝑝𝑆𝑆𝑆𝑆(1 −𝑝𝑝𝑆𝑆𝑆𝑆)
𝑛𝑛𝑆𝑆𝑆𝑆
 ≤𝑝𝑝𝐹𝐹𝐹𝐹−𝑝𝑝𝑆𝑆𝑆𝑆≤𝑝𝑝𝐹𝐹𝐹𝐹−𝑝𝑝𝑆𝑆𝑆𝑆+ 𝑧𝑧𝛼𝛼ඨ𝑝𝑝𝐹𝐹𝐹𝐹(1 −𝑝𝑝𝐹𝐹𝐹𝐹)
𝑛𝑛𝐹𝐹𝐹𝐹
+ 𝑝𝑝𝑆𝑆𝑆𝑆(1 −𝑝𝑝𝑆𝑆𝑆𝑆)
𝑛𝑛𝑆𝑆𝑆𝑆
 
In order for the ST sensor to be equivalent (≥) the FO sensor, the lower bound of the confidence 
interval should be < 0. Figure 12 illustrates a range of possible confidence intervals in a study with 
nFO = nST = 98, and a pFO = 96%. In this case, if the ST sensitivity (pST) is 89% or lower, the lower 
confidence interval is greater than zero, and the ST sensitivity would be considered significantly 
less than the FO sensitivity. 
 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
35 of 58 
 
Figure 12. Examples of confidence intervals at various ST sensitivities, assuming FO sensitivity = 
96%. 
Quality Assurance 
As the research sponsor, ivWatch, LLC will continually monitor the research studies to ensure 
subject safety and data validity. Unlike multicenter studies, all aspects of the study are performed 
with ivWatch personnel facilitating the quality assurance process. 
The first component of the quality assurance program is ensuring the research personnel have the 
correct training to perform the studies. All study personnel (investigators, research staff, study 
monitors) will have the proper training (HIPAA and CITI) for conducting clinical trials prior to the 
start of the study. The subject screening will be performed by a registered nurse. 
The second component of the quality assurance program is the monitoring of studies to ensure 
the procedures outlined in this document are followed. This includes the procedures for data 
collection (ivWatch research system operation), data storage, and data validation.  
The third component of the quality assurance program is monitoring the security of study data. As 
described in the data management section, study data stored in the database are password 
protected and restricted to authorized users. Any changes to the database are tracked. The case 
report forms do not contain subject identifiers. All paper health history forms will be stored in a 
locked filing cabinet. 
Monitoring Plan 
The Monitor will complete the initiation of the investigation site prior to beginning the study. Based 
upon the length and complexity of this study, the Monitor will conduct periodic visits of the 
investigation site.  Minimally, the Monitor will visit the site prior to the closing out the study and 
complete the Monitoring Visit Checklist and Report using SF-1001020. 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
36 of 58 
Expected Outcomes of the Study 
The expected outcome of this study is an understanding of whether the ivWatch SmartTouch 
sensor will be as effective as the Model 400 for detecting early stage infiltrations. 
Publication Policy 
ivWatch will approve any publication released as a result of this research study. Results of the study 
may be published in various healthcare segments relating to vascular access, such as the Infusion 
Nurses Society and Association for Vascular Access. 
Duration of the Study 
Each study will last up to approximately 2 hours. The entire study is expected to require less than 
two months to complete. 
Anticipated Problems 
Project timing and budgeting difficulties are not anticipated for this research project.  First, the 
study consists of approximately 115 participants (98 accepted case studies). ivWatch is confident 
the necessary data can be collected from 98 subjects within 1-2 months. Second, the budget for 
this project is funded by ivWatch, LLC.  ivWatch will pay for costs specified in the clinical trial 
agreement. 
Ethics 
ivWatch, LLC will follow ethical and regulatory guidelines while conducting this study. The 
investigators will not proceed with the study until the consent form has been signed by each 
volunteer subject. Prior to obtaining informed consent signatures, the study will be verbally 
described to each volunteer and the investigators will address any outstanding questions or 
concerns. The investigators will receive the proper informed consent training prior to the study. 
Overall, the clinical investigation shall be conducted in accordance with the ethical principles 
that have their origin in the Declaration of Helsinki. Vulnerable populations will not be targeted for 
enrollment. 
Good Clinical Practice 
Good Clinical Practice (GCP) according to the ICH guidelines and ISO 14155 Clinical Investigation 
of Medical Devices will be followed for this study. In addition, ivWatch clinical investigations follow 
ICH E6, and FDA 21CFR50,54, 56 and 812.   

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
37 of 58 
 
Clinical Trial Insurance 
Insurance is provided to study subjects for medical expenses incurred from bodily injury during 
clinical testing. 
Informed Consent Forms 
Please see the attached informed consent form. 
Deviations from the Protocol 
Investigators will notify the IRB of any deviation from the investigational plan/protocol to protect 
the life or physical well-being of a subject in an emergency as soon as possible, but not later than 
five (5) working days after the emergency occurred. 
Serious Adverse Events / Device Deficiencies 
Serious adverse events and/or device deficiencies are not anticipated, as this general protocol 
has been followed with this device and other research systems in several previous studies. All 
serious and unanticipated events will be reported as soon as possible, and no later than ten (10) 
working days after becoming aware of the event. Other non-serious adverse events and device 
deficiencies will be recorded in the case report form. 
 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
38 of 58 
 Case Report Form 
1. General Study Information 
Case Report Form #: 
 
Study Start Date (MM/DD/YYYY): 
 
 
2. Inclusion Criteria  
 
Signed consent  
 
Subject 18 years or older 
 
Health form approved 
 
3. General Subject Information  
Gender:   
 
Male 
 
Female 
Age: 
 
 
years 
 
4. Body Measurements  
 
 
Weight:  
lb 
 
Height: 
 
 
in 
 
 
Systolic Blood 
Pressure:  
mmHg 
 
Diastolic Blood 
Pressure:  
mmHg 
Forearm Circumference 
Left forearm:  
mm 
Right forearm:  
mm 
 
5. Skin Pigmentation (Check one) 
 
 
Skin Type Score: 
 
 
Fitzpatrick Skin Type: 
 
 
Light 
 
 
Medium 
 
 
Dark 
 
6. Study Configuration 
 
Left Site 
Right Site 
Sensor 
(Select One Per Side) 
 
Fiber Optic 
 
SmartTouch 
 
 
SmartTouch 
 
Fiber Optic 
 
Site 
(Select One) 
 
Hand 
 
Forearm 
 
Infiltration Rate 
 
cc/hr 
 
 
IRB #: Pro00032924 
Principle Investigator: Jason Naramore 
Revision Date: 3/12/2019 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
39 of 58 
CRF# _______ 
7. Pre-Study Information 
 
Left Site 
Right Site 
SmartTouchTM Sensor Serial No. 
 
 
Patient Cable Serial No. 
 
 
Extension Module Serial No. 
 
 
IPM Serial Number  
 
 
Fiber Optic Cable Serial No. 
 
 
Fiber Optic Receptacle Lot No. 
 
 
Vein Viewer Photo (File ID) 
 
 
Pre-Insertion Photo (File ID) 
 
 
Ultrasound Images  
without Calipers (Time) 
(In-Plane) 
(Out-Plane) 
(In-Plane) 
(Out-Plane) 
Ultrasound Images  
with Calipers (Time) 
(In-Plane) 
(Out-Plane) 
(In-Plane) 
(Out-Plane) 
Catheter Depth (mm) 
(In-Plane) 
(Out-Plane) 
(In-Plane) 
(Out-Plane) 
Post-Insertion Photo (File ID) 
 
 
Site Circumference (mm) 
 
 
 
 
 
 
 
 
 
IRB #: Pro00032924 
Principle Investigator: Jason Naramore 
Revision Date: 3/12/2019 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
40 of 58 
CRF# _______ 
8. Study Information 
 
Left Site 
Right Site 
IPM Start Time (HH:MM:SS) 
 
 
Staff Initials (Verify correct pump rate) 
 
 
Pump Start Time (HH:MM:SS) 
 
 
Pump Stop Time (HH:MM:SS) 
 
 
Total Volume Infused (mL) 
 
 
IPM Stop Time (HH:MM:SS) 
 
 
 
9. Post-Study Information   
 
Left Site 
 Right Site 
Site Circumference (mm) 
 
 
Dressed Site Photo (File ID) 
 
 
Vein Viewer (File ID) 
 
 
Ultrasound Images  
without Calipers (Time) 
(In-Plane) 
(Out-Plane) 
(In-Plane) 
(Out-Plane) 
Ultrasound Images  
with Calipers (Time) 
(In-Plane) 
(Out-Plane) 
(In-Plane) 
(Out-Plane) 
Catheter Depth (mm) 
(In-Plane) 
(Out-Plane) 
(In-Plane) 
(Out-Plane) 
Catheter Displacement (mm) 
 
 
Bare Site Photo (File ID) 
 
 
 
 
 
IRB #: Pro00032924 
Principle Investigator: Jason Naramore 
Revision Date: 3/12/2019 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
41 of 58 
CRF# _______ 
10. Miscellaneous Notes  
Are there any additional comments related to the case study? 
Please include comments below.  
 
 
Yes 
 
No 
 
N/A 
 
11. Device Deficiencies / Malfunctions  
Did the investigation device not perform as expected by the 
intended use when used per the instructions and the protocol? 
 
Could this deficiency/malfunction have led to an 
adverse event?  
 
If yes to either question, please explain: 
 
 
Yes 
 
No 
 
N/A 
 
Yes 
 
No 
 
N/A 
 
12. Adverse Events  
Did the patient experience any unexpected harm associated 
with the ivWatch Model 400 device or the research protocol? 
 
Is this event reportable?  
 
If yes to either question, please explain: 
 
 
 
Yes 
 
No 
 
N/A 
 
Yes 
 
No 
 
N/A 
 
13. Authorization  
I certify that to the best of my  
knowledge, 
the 
information  
contained in this form is true  
and correct. 
 
 
 
Signature of Investigator 
 
Date 
 
 
 
Printed Name of Investigator 
 
 
IRB #: Pro00032924 
Principle Investigator: Jason Naramore 
Revision Date: 3/12/2019 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
42 of 58 
Pre-Screening Form 
Name: (Last)  
 
  (First)   
 
 (Middle Initial)  
 
Date of Birth: (MM/DD/YYYY)   
 
 
Phone:   
 
 Email:   
 
 
 
Medical Questions 
Yes* 
No 
1. 
Do you have any allergies? 
2. 
Are you currently participating in any other medical studies? 
3. 
Do you have a history of fainting when needles are used on you? 
4. 
Are you taking any medications? 
 
 
5. 
Have you been hospitalized in the past 14 days? 
 
 
6. 
Have you been sick or had an infection in the past 14 days? 
 
 
7. 
Have you received IV therapy in the past 14 days? 
 
 
8. 
Do you have tattoos covering more than half of your inner forearms or back of your hands? 
 
 
9. 
Do you have significant scar tissue on your inner forearms or back of your hands? 
 
 
10. Do you have an absence of sensation in your arms? 
 
 
11. (For females only) Are you currently pregnant? 
 
N/A 
*If yes to any of the above, please explain: 
 
 
 
N/A 
 
 
 
**Eligible 
 
Ineligible 
 
ivWatch Staff Signature 
_____________________________ Date _____________ 
 
**If “yes” is checked for any of the shaded “Yes” boxes and there isn’t acceptable reasoning, the subject is ineligible. If 
you are unsure about the subject’s eligibility, consult the physician/nurse on staff to determine eligibility. 
 
Date 
 
Time 
 
Consulted physician/nurse 
 
Notes from consultation: 
 
 
 
 
 
 
N/A 
Medical History 
Condition 
Yes* 
No 
Condition 
Yes* 
No 
Bleeding Disorder 
 
 
Immune Deficiency Disorders 
 
 
Cardiopulmonary Disorders 
 
 
Lymphedema 
 
 
Clotting Disorders 
 
 
Radiation/Chemotherapy 
 
 
Currently anemic  
 
 
Seizures/Epilepsy  
 
 
Hepatitis  
 
 
Stroke 
 
 
HIV/Aids 
 
 
Tuberculosis  
 
 
*If yes to any shaded areas above, please explain: 
 
 
 
N/A 
If you have any other medical conditions we should be aware of, please explain below. 
If yes, please explain: 
 
 
 
N/A 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
43 of 58 
 Health History Form 
Name: (Last)  
 
  (First)   
 
 (Middle Initial)  
 
Date of Birth: (MM/DD/YYYY)   
 
 
Address: (Street)  
 
 
 
(City)   
 (State)  
  (Zip)  
 
 
 
 
 
Phone:   
 
 Email:   
 
 
 
Medical Questions 
Yes* 
No 
1. 
Do you have any allergies? 
2. 
Are you currently participating in any other medical studies? 
3. 
Do you have a history of fainting when needles are used on you? 
4. 
Are you taking any medications? 
 
 
5. 
Have you been hospitalized in the past 14 days? 
 
 
6. 
Have you been sick or had an infection in the past 14 days? 
 
 
7. 
Have you received IV therapy in the past 14 days? 
 
 
8. 
Do you have tattoos covering more than half of your inner forearms or back of your hands? 
 
 
9. 
Do you have significant scar tissue on your inner forearms or back of your hands? 
 
 
10. Do you have an absence of sensation in your arms? 
 
 
11. (For females only) Are you currently pregnant? 
 
N/A 
*If yes to any of the above, please explain: 
 
N/A 
 
 
Temperature: __________ ˚F 
 
**Eligible 
 
Ineligible 
 
ivWatch Staff Signature 
_____________________________ Date _____________ 
 
Medical History 
Condition 
Yes* 
No 
Condition 
Yes* 
No 
Bleeding Disorder 
 
 
Immune Deficiency Disorders 
 
 
Cardiopulmonary Disorders 
 
 
Lymphedema 
 
 
Clotting Disorders 
 
 
Radiation/Chemotherapy 
 
 
Currently anemic  
 
 
Seizures/Epilepsy  
 
 
Hepatitis  
 
 
Stroke 
 
 
HIV/Aids 
 
 
Tuberculosis  
 
 
*If yes to above, please explain: 
 
 
N/A 
If you have any other medical conditions we should be aware of, please explain below. 
If yes, please explain: 
 
N/A 
**If “yes” is checked for any of the shaded “Yes” boxes and there isn’t acceptable reasoning, the subject is ineligible. If 
you are unsure about the subject’s eligibility, consult the physician/nurse on staff to determine eligibility. 
 
Date 
 
Time 
 
Consulted physician/nurse 
 
Notes from consultation: 
 
 
 
 
 
 
N/A 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
44 of 58 
Skin Pigmentation Worksheet 
Skin Pigmentation Worksheet 
CRF Number: _________ 
Reaction to Sun Exposure 
Score 
0 
1 
2 
3 
4 
What happens 
when you stay in 
the sun too long? 
Painful 
redness, 
blistering, 
peeling 
Blistering 
followed by 
peeling 
Burns 
sometimes 
followed by 
peeling 
Rare burns 
Never had 
burns 
To what degree 
do you turn 
brown? 
Hardly or not 
at all 
Light color 
tan 
Reasonable 
tan 
Tan very 
easy 
Turn dark 
brown 
quickly 
Do you turn brown 
within several 
hours after sun 
exposure? 
Never 
Seldom 
Sometimes 
Often 
Always 
How does your 
face react to the 
sun? 
Very 
sensitive 
Sensitive 
Normal 
Very 
resistant 
Never had a 
problem 
 
Total Score for Reaction to Sun Exposure: ___________ 
 
 
 
 
Tanning Habits 
Score 
0 
1 
2 
3 
4 
When did you last 
expose your body 
to sun (or artificial 
sunlamp/tanning 
cream)? 
More than 3 
months ago 
2-3 months 
ago 
1-2 months 
ago 
Less than a 
month ago 
Less than 2 
weeks ago 
Did you expose 
the area to be 
treated to the 
sun? 
Never 
Hardly ever 
Sometimes 
Often 
Always 
 
Total Score for Tanning Habits: ___________ 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
45 of 58 
 
Skin Pigmentation Worksheet 
CRF Number: _________ 
Genetic Disposition 
Score 
0 
1 
2 
3 
4 
What is the color 
of your eyes? 
Light Blue, 
Gray, Green 
Blue, Gray 
or Green 
Blue 
Dark Brown 
Brownish 
Black 
What is the natural 
color of your hair? 
Sandy Red 
Blond 
Chestnut/ 
Dark Blond 
Dark Brown 
Black 
What is the color 
of your skin (non-
exposed areas)? 
Reddish 
Very Pale 
Pale with 
Beige tint 
Light Brown 
Dark Brown 
Do you have 
freckles on 
unexposed areas? 
Many 
Several 
Few 
Incidental 
None 
 
Total Score for Genetic Disposition: ___________ 
 
Add up the total scores for each of the three sections for your Skin Type Score. 
Skin Type Score 
Fitzpatrick Skin Type 
0-7 
I 
8-16 
II 
17-25 
III 
26-30 
IV 
over 30 
V-VI 
 
 
My Skin Score 
 
 
My Skin Type 
 
 
 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
46 of 58 
Pre-Study Checklist 
CRF#: ________ 
Step 
Role 
Status 
Task 
1.  
Subject 
 
Sign in at the reception desk and show identification. 
2.  
Research 
Assistant 
 
Subject taken to private screening room. 
3.  
Research 
Assistant 
 
Provide informed consent form with description of the study. 
4.  
Research 
Assistant 
 
Discuss study and ask if the subject has questions regarding the 
study and/or their rights as a participant. 
5.  
Subject 
 
Review and either sign consent form or opt-out of study. 
6.  
Research 
subject 
 
Take subject to health screening room. 
7.  
Nurse 
 
Provide health history form to subject.  
8.  
Subject 
 
Complete health history form. 
9.  
Nurse 
 
Ask subject if they have questions regarding the health history 
form. Measure body temperature of the subject and record at 
the bottom of the form. 
10.  
Nurse 
 
Review the completed health history form. If a section is marked 
“yes,” confirm the subject has provided an explanation. If 
necessary, consult with the physician on staff for sections marked 
as “yes” and determine the subject’s eligibility. 
11.  
Nurse 
 
If health history form is accepted, complete Sections 1-3 of the 
Case Report Form. 
12.  
Nurse 
 
Perform health screening of the subject to measure weight, 
height, blood pressure, and forearm circumference. Record 
measurements in Section 4 of the Case Report Form. 
13.  
Nurse 
 
Work through the Subject Pigmentation Worksheet with the 
subject. Calculate the final score for the subject and record in 
Section 5 of the Case Report Form. 
14.  
Nurse 
 
Use personal judgement to determine the skin tone of the subject 
and record in Section 5 of the Case Report Form. 
15.  
Nurse 
 
If the subject has passed the health history form and Sections 1-6 
are completed in the Case Report Form, take subject to the test 
area.  
 
 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
47 of 58 
Data Collection Checklist 
CRF#: ________ 
Step 
Role 
Status Task 
1 
Research 
Assistant 
 
Subject taken to test room. Ensure subject comfort. 
2 
Nurse 
 
Nurse and ultrasound tech to perform hand hygiene. Apply latex-free 
gloves. 
3 
Research 
Assistant 
 
Review Sections 1-6 of the case report form. 
4 
Research 
Assistant 
 
Record the serial/lot numbers of the ivWatch equipment in Section 7 
of the case report form. 
5 
Nurse 
 
On the Fiber Optic IPM, set up the run and verify the cable is 
functioning properly. The IPM should show the placement screen.  
Prepare Site on Left Arm 
6 
Nurse 
 
If necessary, shave the site location. 
7 
Research 
Assistant 
 
Photograph VeinViewer illumination at site. Record File ID of 
VeinViewer Photograph in Section 7 of case report form. 
8 
Research 
Assistant 
 
Photograph bare site. Record File ID of Pre-Insertion Photograph in 
Section 7 of the case report form. 
9 
Nurse 
 
Clean selected area on subject with CHG Swabstick for 30 seconds 
and allow to air dry for 30 seconds. 
10 
Nurse 
 
Place catheter tip next to a vein typically used for IV therapy. If 
needed, use ultrasound during placement. Discard needle in sharps 
container.  
11 
US Tech 
 
Record post-insertion ultrasound images of injection site.  
• 
Capture in-plane ultrasound image of catheter and measure 
depth of catheter tip.  
• 
Capture out-of-plane ultrasound image of catheter and measure 
depth of catheter tip. 
• 
Record ultrasound file IDs (time) and catheter depth in section 7 
of the case report form. If images are in the same minute, label the 
second image with “a”. 
• 
Remove ultrasound gel from site using gauze and clean area with 
two alcohol wipes. 
12 
Nurse 
 
Connect IV Tubing to Catheter 
• 
Remove air from catheter hub using normal saline. 
• 
Connect IV tubing to catheter. 
• 
Dry area around catheter using gauze. 
• 
Place a piece of tape over catheter to hold in place. 
13 
Nurse 
 
The configuration is not over dressing. 
a. Apply occlusive dressing over injection site. 
b. Adhere ivWatch sensor on the same side of the vein as the 
catheter while using spare catheter for placement. 
c. Verify sensor is approximately 5 mm from the catheter. 
14 
Nurse 
 
Perform cable management and secure sensor cable to IV tubing 
using medical tape. 
15 
Nurse 
 
Check that the sensor is connected to the corresponding ivWatch 
patient monitor (IPM). 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
48 of 58 
16 
Research 
Assistant 
 
Photograph monitoring site. Record File ID of Post-Insertion 
Photograph in Section 7 of case report form. 
Prepare Site on Right Arm 
17 
Research 
Assistant 
 
Photograph VeinViewer illumination at site. Record File ID of 
VeinViewer Photograph in Section 7 of case report form. 
18 
Research 
Assistant 
 
Photograph bare site. Record File ID of Pre-Insertion Photograph in 
Section 7 of the case report form. 
19 
Nurse 
 
Clean selected area on subject with CHG Swabstick for 30 seconds 
and allow to air dry for 30 seconds. 
20 
Nurse 
 
Place catheter tip next to a vein typically used for IV therapy. If 
needed, use ultrasound to place the catheter. Discard needle in 
sharps container. 
21 
US Tech 
 
Record post-insertion ultrasound images of injection site. 
• 
Capture in-plane ultrasound image of catheter and measure 
depth of catheter tip. 
• 
Capture out-of-plane ultrasound image of catheter and measure 
depth of catheter tip. 
• 
Record ultrasound file IDs and catheter depth in section 7 of the 
case report form. If the images are in the same minute, label the 
second image with “a”. 
• 
Remove ultrasound gel from site using gauze and clean area with 
two alcohol wipes.  
22 
Nurse 
 
Connect IV Tubing to Catheter 
• 
Remove air from catheter hub using normal saline. 
• 
Connect IV tubing to catheter. 
• 
Dry area around catheter using gauze. 
• 
Place a piece of tape over catheter to hold in place. 
23 
Nurse 
 
The configuration is not over dressing. 
a. Apply occlusive dressing over injection site. 
b. Adhere ivWatch sensor on the same side of the vein as the 
catheter while using the spare catheter for placement. 
c. Verify sensor is approximately 5 mm from the catheter.  
24 
Nurse 
 
Perform cable management and secure sensor cable to IV tubing 
using medical tape. 
25 
Nurse 
 
Check that the sensor is connected to the corresponding ivWatch 
patient monitor (IPM). 
26 
Research 
Assistant 
 
Photograph monitoring site. Record File ID of Post-Insertion 
Photograph in Section 7 of case report form. 
27 
Nurse 
 
Clean ultrasound probe by wiping thoroughly with Sani-Cloth Wipe. 
 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
49 of 58 
Data Collection 
28 
Nurse 
 
Site Circumference Measurement. Mark a line on the dressing 
indicating where to place the measuring tape, such that the 
circumference is measured at the approximate location of the 
catheter tip. Complete this on both arms. Record Site Circumferences 
in Section 7 of case report form. 
29 
Nurse 
 
Start data acquisition on IPMs. Using the digital clock, 
record acquisition start time in Section 8 of case report 
form. 
t = 0 min 
30 
Nurse 
 
Start IV pumps. Record start times in Section 8 of case 
report form. 
t = 5 min 
31 
Nurse 
 
Record stop times in Section 8 of case report form. 
10 mL infiltrated 
32 
Nurse 
 
Stop data acquisition on IPM. Record acquisition stop 
time (digital clock) in Section 8 of case report form. 
5 minutes after 
both pumps 
stopped 
33 
Nurse 
 
Measure circumference of the subcutaneous injection sites on both 
arms using previous markings. Record Site Circumferences in Section 
9 of the case report form. 
34 
Research 
Assistant 
 
Begin data transfer on the IPMs. 
Left Arm Post Study Assessment 
35 
Research 
Assistant 
 
Photograph monitoring site. Record File ID of Dressed Site Photograph 
in Section 9 of case report form. 
36 
Nurse 
 
Remove occlusive dressing and ivWatch sensor from site. Mark 
location of sensor head. 
37 
Research 
Assistant 
 
Photograph VeinViewer illumination at site. Record File ID of 
VeinViewer Photograph in Section 9 of case report form. 
38 
US Tech 
 
Record ultrasound images of injection site after infiltration complete. 
• 
Capture in-plane ultrasound image of catheter and measure 
catheter depth. 
• 
Capture out-of-plane ultrasound image of catheter and measure 
catheter depth. 
• 
Record ultrasound file IDs and catheter depth in section 9 of the 
case report form. If the images are in the same minute, label the 
second image with “a”. 
• 
Remove ultrasound gel from site using gauze. 
• 
Measure displacement between catheter tip and sensor. Record 
in Section 9 of case report form. 
39 
Nurse 
 
Remove catheter. Apply light pressure until bleeding stops. Try not to 
displace infiltrated fluid. 
40 
Research 
Assistant 
 
Photograph bare site for record of skin integrity. Record File ID of Bare 
Site Photograph in Section 9 of case report form. 
41 
Nurse 
 
Apply adhesive bandage to site. 
Right Arm Post Study Assessment 
42 
Research 
Assistant 
 
Photograph monitoring site. Record File ID of Dressed Site Photograph 
in Section 9 of case report form. 
43 
Nurse 
 
Remove occlusive dressing and ivWatch sensor from site. Mark 
location of sensor head. 
44 
Research 
Assistant 
 
Photograph VeinViewer illumination at site. Record File ID of 
VeinViewer Photograph in Section 9 of case report form. 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
50 of 58 
45 
US Tech 
 
Record ultrasound images of injection site after infiltration complete. 
• 
Capture in-plane ultrasound image of catheter and measure 
catheter depth. 
• 
Capture out-of-plane ultrasound image and measure catheter 
depth. 
• 
Record ultrasound file IDs and catheter depth in section 9 of the 
case report form. If the images are in the same minute, label the 
second image with “a”. 
• 
Remove ultrasound gel from site using gauze. 
• 
Measure displacement between catheter tip and sensor and 
record in Section 9 of case report form. 
46 
Nurse 
 
Remove catheter. Apply light pressure until bleeding stops. Try not to 
displace infiltrated fluid. 
47 
Research 
Assistant 
 
Photograph bare site for record of skin integrity. Record File ID of Bare 
Site Photograph in Section 9 of case report form. 
48 
Nurse 
 
Apply adhesive bandage to site. 
49 
Nurse 
 
Clean ultrasound probe by wiping with Sani-Cloth Wipe. 
Study Completion 
50 
Research 
Assistant 
 
Complete Sections 10-13 in case report form. 
51 
Research 
Assistant 
 
Take subject to front reception desk and provide study participation 
payment. Provide a copy of the patient’s ICF should they have 
questions after leaving. 
52 
Subject 
 
Sign and date the check-out sheet to verify receipt of payment. The 
subject leaves. 
53 
Research 
Assistant 
 
Remove tape connecting IV tubing and sensor cable. Dispose of the 
IV tubing. Clean the ivWatch sensor with hospital-grade disinfectant 
wipes. Bundle the cable and store on the IV pole. 
54 
Research 
Assistant 
 
Clean the test area.   
55 
Research 
Assistant 
 
Transfer the following to the network server: 
1. ivWatch Data (via USB drive) 
2. Ultrasound Images (via USB drive) 
3. Camera Images 
56 
Research 
Assistant 
 
Store paperwork (case report form and checklists) in manila folder. 
Provide paperwork containing private health information to HIPAA 
officer for separate and secure storage. 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
51 of 58 
FDA Clearance Letters for ivWatch Model 400 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
52 of 58 
 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
53 of 58 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
54 of 58 
  

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
55 of 58 
 Investigator Signatures 
Example [I certify that I am knowledgeable about the regulations and policies governing research 
with human subjects. I have reviewed this document and agree to conduct the study in 
accordance with the approved protocol.] 
 
 
Principal Investigator 
Name: 
William J. Naramore 
Signature: 
 
Date: 
 
 
 
Investigator 
Name: 
Susan Brown, MSN, MSED, BA, VA-BC 
Signature: 
 
Date: 
 
 
 
Investigator 
Name: 
Gregory J. Schears, M.D. 
Signature: 
 
Date: 
 
 
 
Investigator 
Name: 
Marisa A. Cole 
Signature: 
 
Date: 
 
 
 
 
 
 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
56 of 58 
 Statistical Monte Carlo Analysis 
clear variables; 
close all; 
clc; 
  
% Parameters of the Monte Carlo Simulation 
simulation.number_of_trials = 1000000; 
simulation.alternative_hypothesis_sensitivity = 0.90; 
  
% Perform the Monte Carlo Simulation (method included below) 
results = simulate_study2(simulation); 
  
% Generate figure of simulated distributions 
figure; 
h(1) = bar(results.bins, results.null_sensitivities_bins/max(results.null_sensitivities_bins)); 
hold on; 
h(2) 
= 
bar(results.bins, 
results.alternative_sensitivities_bins/max(results.alternative_sensitivities_bins)); 
set(h(2),'FaceColor','r'); 
set(get(h(1),'Children'),'EdgeAlpha',0) 
set(get(h(2),'Children'),'EdgeAlpha',0) 
set(get(h(1),'Children'),'FaceAlpha',0.5) 
set(get(h(2),'Children'),'FaceAlpha',0.5) 
xlim([0 110]) 
xlabel('Infiltration Sensitivity (%)') 
h_legend = legend('Null Hypothesis', 'Alternative Hypothesis'); 
set(h_legend,'Location','NorthWest') 
children = get(h_legend,'Children'); 
alt_box = get(children(1),'Children'); 
null_box = get(children(3),'Children'); 
set(alt_box,'FaceAlpha',0.5); 
set(null_box,'FaceAlpha',0.5); 
set(alt_box,'EdgeAlpha',0); 
set(null_box,'EdgeAlpha',0); 
set(h_legend,'EdgeColor',[1 1 1]); 
hold on; 
plot(results.threshold*[1 1], [0,1],'r-') 
  
% Printe statistical metrics to MATLAB console 
fprintf(1,'Threshold: 
%f 
(%f 
H0 
cases 
below 
this 
threhsold)\r', 
results.threshold, 
results.confidence); 
fprintf(1,'Statistical Power (1-Beta): %f\r', results.power); 
fprintf(1,'Alpha: %f (one-sided)\r', results.alpha); 
fprintf(1,'Beta: %f\r',results.beta); 
fprintf(1,'Mean Null: %f', results.mean_null); 
  
% Generate plot showing statistical power as a function of the sensitivity  
% of the alternative hypothesis 
alternative_hypotheses = [0.25:0.01:1]; 
h = waitbar(0,'Please be patient Jason'); 
for i=1:length(alternative_hypotheses) 
    simulation.alternative_hypothesis_sensitivity = alternative_hypotheses(i); 
    results = simulate_study2(simulation); 
    powers(i) = results.power; 
    waitbar(i/length(alternative_hypotheses),h); 
end 
close(h); 
figure; 
plot(alternative_hypotheses*100,100* powers,'r-'); 
xlabel('Device Sensitivity (Alternative Hypothesis)'); 
ylabel('Statistical Power (%)'); 
title('70 PIV Site Study') 
grid 
  
% Save figure 
%gtb_save_figure(figure(1),'MonteCarloAnalysis') 
%gtb_save_figure(figure(2),'StatisticalPowerAnalysis') 
  

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
57 of 58 
 
function [results] = simulate_study2(simulation) 
  
% Load study simulation details 
number_of_trials = simulation.number_of_trials; 
number_of_subjects = 90; 
% Load the alternative hypothesis sensitivity (predicted sensitivity of 
% ivWatch device) 
alternative_hypothesis_sensitivity = simulation.alternative_hypothesis_sensitivity; 
  
% The volume limit  
Vlim = 10; 
  
% List of rates 
rates = [5; 25; 50; 75; 100; 125; 150]; 
  
% Detection by the perfect clinician is uniformly distirbuted between 0 and 
% 60 minutes 
  
for i=1:number_of_trials 
    % Detection times uniformly distributed between 0 and 60 minutes 
    detection_matrix_null = 60*rand(7,14); 
  
    % The perfect clinician detects the infiltration if 
    % (detection_matrix_null)<Vlim/R*60 
    sensitivity_matrix_null = detection_matrix_null < Vlim./repmat(rates,1,14)*60; 
  
    % Sensitivity for the perfect clinician for this particular trial 
    null_sensitivities(i) 
= 
sum(sensitivity_matrix_null(:))/length(sensitivity_matrix_null(:))*100; 
  
    % Generate matrix with uniformly distributed numbers between 0 and 1. 
    sensitivity_matrix_alt = rand(7,14); 
     
    % Sensitivity for the ivWatch device for this particular trial 
    alternative_sensitivities(i) 
= 
sum(sensitivity_matrix_alt(:)<alternative_hypothesis_sensitivity) 
/ 
length(sensitivity_matrix_alt(:))*100; 
end 
  
% Bin the results 
bins = (1:number_of_subjects)/number_of_subjects*100; 
null_sensitivities_bins = hist(null_sensitivities,bins); 
alternative_sensitivities_bins = hist(alternative_sensitivities,bins); 
  
% Figure out a threshold where > 95% of the clinician sensitivities are 
% less than this threshold 
null_cumsum = cumsum(null_sensitivities_bins)./ sum(null_sensitivities_bins); 
pos = find(null_cumsum > 0.95); 
threshold = (bins(pos(1))+bins(pos(1)+1))/2; 
  
% Calculate statistical metrics 
power = sum(alternative_sensitivities_bins(bins > threshold))/sum(alternative_sensitivities_bins); 
alpha = sum(null_sensitivities_bins(bins > threshold))/sum(null_sensitivities_bins); 
beta = sum(alternative_sensitivities_bins(bins < threshold))/sum(alternative_sensitivities_bins); 
  
% Output results 
results.threshold = threshold; 
results.confidence = 1-alpha; 
results.power = power; 
results.alpha = alpha; 
results.beta = beta; 
results.bins = bins; 
results.null_sensitivities_bins = null_sensitivities_bins; 
results.alternative_sensitivities_bins = alternative_sensitivities_bins; 
results.mean_null = mean(null_sensitivities); 
 
 

IVW-CLR-CS27-400 
ivWatch SmartTouch Sensor: 
Device Validation for Infiltrated Tissues 
 
CONFIDENTIAL 
58 of 58 
 Bibliography 
[1]  E. M. Kagel and G. M. Rayan, "Intravenous catheter complications in the hand and forearm," 
J Trauma-Injury Infection & Crit Care, vol. 56, no. 1, pp. 123-127, Jan 2004.  
[2] R. E. Helm, J. D. Klausner, J. D. Klemperer, L. M. Flint and E. Huang, “Accepted but 
unacceptable: peripheral IV catheter failure,” J Infus Nurs, vol. 38, no. 3, pp. 189-203, May 
2015. 
[3]  C. M. Rickard, J. Webster, M. C. Wallis, N. Marsh, M. R. McGrail, V. French, L. Foster, P. 
Gallagher, J. R. Gowardman, L. Zhang, A. McClymont and M. Whitby, "Routine versus 
clinically indicated replacement of peripheral intravenous catheters: a randomised 
controlled equivalence trial," Lancet, vol. 380, pp. 1066-1074, 2012.  
[4]  D. T. Gault, "Extravasation injuries," Br J Plast Surgery, vol. 46, no. 2, pp. 91-96, Mar 1993.  
[5]  S. Phelps and R. A. Helms, "Risk factors affecting infiltration of peripheral venous lines in 
infants," J Pediatr, vol. 111, no. 3, pp. 384-389, Sep 1987.  
[6]  S. Masoorli, "Infusion therapy lawsuits," J. Intravenous Nursing, vol. 18, pp. 88-91, 1995.  
[7]  J. B. B. a. C. L. Jacobs, "Contrast media reactions and extravasation: Relationship to 
intravenous injection rates," Radiol., vol. 176, pp. 411-416, 1998.  
[8] M. C. Wallis, M. McGrail, J. Webster, N. Marsh, J. Gowardman, E. G. Playford, and C. M. 
Rickard, “Risk factors for peripheral intravenous catheter failure: a multivariate analysis of 
data from a randomized controlled trial,” Infect Control Hosp Epidemiol, vol. 35, no. 1, pp. 
63-68, Jan 2014. 
[9]  J. Pettit, "Assessment of Infant with a Peripheral Intravenous Device," Adv Neonatal Care, vol. 
3, no. 5, 2003.  
[10] Infusion Nurses Society, in Infusion Nursing: An Evidence-Based Approach, St. Louis, Missori, 
Elsevier, 2010, pp. 516-517.