Validation Study: Extended Wear Performance of the Zio Monitor - SHASTA II
Phase: NA
Conditions: Cardiac Arrhythmia
Sponsor: iRhythm Technologies, Inc.

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 1 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
 
 
 
 
 
 
 
 
 
Validation Study: Extended Wear Performance of the Zio monitor – SHASTA II 
Protocol Number 
IRT-003-2024 
Version Number 
1.0 
Date 
October 31, 2024 
Principal Investigator 
Minang Turakhia, MD 
Planned Number of Locations and Region(s) 
Up to Five Study Centers in the US 
Protocol Author  
TJ Battisti, Ph.D. 
 
 
 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 2 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
 
 
 
Task 
Name 
Function 
Signature 
Date 
Written 
by 
TJ Battisti 
Sr. Clinical 
Research Scientist 
 
 
Reviewed 
by 
Chevy Brown 
Sr. Manager, 
Clinical Research 
 
 
Reviewed 
by 
Christine Dunn 
Director, 
Regulatory Affairs 
 
 
Approved 
by 
Charlotte Bame 
Director, Clinical 
Research 
Operations 
 
 
Approved 
by 
Chanda Owens 
VP, Quality 
Assurance 
 
 
Approved 
by 
Minang Turakhia 
Chief Medical & 
Scientific Officer & 
EVP, Product 
Innovation 
 
 
Approved 
by 
Vladimir Fokin 
Director, Data 
Management and 
Biostatistics 
 
 
Approved 
by 
Kevin Clarkson 
Sr. Director, 
Product 
Management 
 
 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891
11/15/2024
11/15/2024
11/15/2024
11/15/2024
11/15/2024
11/15/2024
11/15/2024
11/15/2024

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 3 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
 
Table of Contents 
TABLE OF CONTENTS .................................................................................................................. 3 
COMPLIANCE STATEMENT .......................................................................................................... 6 
INVESTIGATOR SIGNATURE PAGE ............................................................................................. 7 
PROTOCOL SUMMARY ................................................................................................................. 8 
1.0 
INTRODUCTION ................................................................................................................ 11 
1.1 
Study Design .................................................................................................................. 11 
1.2 
Study Objectives ............................................................................................................. 11 
2.0 
BACKGROUND AND RATIONALE .................................................................................... 11 
2.1 
Name of the Device ........................................................................................................ 12 
2.2 
Intended Indication for Use ............................................................................................. 12 
2.3 
Description of the Device ................................................................................................ 12 
2.4 
Number of Participants ................................................................................................... 14 
2.5 
Overall Flow of the Study and Follow-up Schedule ......................................................... 14 
2.5.1 Study Safety Committee ............................................................................................. 16 
3.0 
STUDY PERFORMANCE OBJECTIVES AND ADDITIONAL MEASURES ........................ 16 
3.1 
Wear Time Performance Objective ................................................................................. 16 
3.2 
Analyzable Time Performance Objective ........................................................................ 16 
3.3 
Safety Measures ............................................................................................................. 16 
3.4 
Additional Device Measures ........................................................................................... 17 
3.5 
Other Measures .............................................................................................................. 17 
4.0 
PARTICIPANT SELECTION AND WITHDRAWAL ............................................................. 17 
4.1 
Participant Recruitment Population and Retention .......................................................... 17 
4.2 
Participant Screening and Informed Consent .................................................................. 17 
4.2.1 Participant Screening .................................................................................................. 17 
4.2.2 Informed Consent ....................................................................................................... 18 
4.2.3 Disclosure of Participant Personal Contact Information ............................................... 18 
4.3 
Eligibility Criteria ............................................................................................................. 18 
4.3.1 Inclusion Criteria ......................................................................................................... 19 
4.3.2 Exclusion Criteria ........................................................................................................ 19 
4.4 
Participant Enrollment and Inclusion ............................................................................... 19 
4.5 
Participant Payment........................................................................................................ 19 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 4 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
4.6 
Participant Discontinuation ............................................................................................. 20 
4.6.1 Lost-to-Follow-up: ....................................................................................................... 20 
4.7 
Number of Participants Required to be Included in the Study ......................................... 20 
4.8 
Estimated Time Needed to Enroll this Number ............................................................... 20 
4.9 
Expected Duration of Each Participant’s Role ................................................................. 20 
4.10 
Total Expected Duration of the Study ............................................................................. 21 
4.11 
Study Completion ........................................................................................................... 21 
5.0 
BASELINE VISIT AND FOLLOW-UP ASSESSMENTS ...................................................... 21 
5.1 
Baseline (Visit 1) ............................................................................................................. 21 
5.2 
Patch Wear Period ......................................................................................................... 22 
5.3 
Protocol Required Medications ....................................................................................... 22 
5.4 
7-Day and 14-Day (+ 3 days) Participant (Phone Call Visit 2 & 3) ................................... 22 
5.5 
21-Day (+3 days) Participant Follow-up (Visit 4) ............................................................. 22 
5.6 
30-Day (±3 days) Participant Follow-up (Visit 5) ............................................................. 23 
6.0 
ADVERSE EVENTS ........................................................................................................... 24 
6.1 
Definitions ....................................................................................................................... 25 
6.1.1 Adverse Event ............................................................................................................ 25 
6.1.2 Serious Adverse Event ............................................................................................... 25 
6.1.3 Device Malfunction ..................................................................................................... 25 
6.2 
Device Relationship ........................................................................................................ 26 
6.2.1 Unanticipated (Serious Adverse) Device Effect [U(S)ADE] ......................................... 26 
6.3 
Adverse Event/Device Deficiency/Product Experience Reporting ................................... 26 
6.3.1 Adverse Event Reporting ............................................................................................ 26 
6.3.2 Unanticipated Serious Adverse Device Effect Reporting ............................................. 26 
6.3.3 Device Deficiency/Device Malfunction Reporting ........................................................ 26 
6.3.4 Adverse Event Reporting to Country Regulatory Authorities by the Sponsor .............. 27 
7.0 
STATISTICAL ANALYSIS .................................................................................................. 27 
7.1 
Analysis Population ........................................................................................................ 27 
7.2 
Sample Size Calculations and Assumptions ................................................................... 27 
7.3 
Planned Interim Analyses ............................................................................................... 27 
7.4 
Statistical Analyses ......................................................................................................... 27 
7.4.1 Subgroup Analysis ...................................................................................................... 28 
8.0 
QUALITY CONTROL AND QUALITY ASSURANCE .......................................................... 28 
8.1 
Selection of Study Site Locations and Investigators ........................................................ 28 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 5 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
8.2 
Protocol Amendments .................................................................................................... 28 
8.3 
Training .......................................................................................................................... 28 
8.3.1 Study Training ............................................................................................................ 28 
8.3.2 Training of Sponsor’s Monitors ................................................................................... 29 
8.4 
Monitoring ....................................................................................................................... 29 
8.5 
Deviations from Protocol ................................................................................................. 29 
8.6 
Quality Assurance Audit ................................................................................................. 30 
9.0 
DATA HANDLING AND RECORD KEEPING ..................................................................... 30 
9.1 
Source Documentation ................................................................................................... 31 
9.2 
Case Report Form Completion ....................................................................................... 31 
9.3 
Direct Access to Source Data/Documents ...................................................................... 31 
9.4 
Record Retention ............................................................................................................ 32 
10.0 
ETHICAL CONSIDERATION .............................................................................................. 32 
10.1 
Institutional Review Board Review .................................................................................. 32 
11.0 
PUBLICATION POLICY ..................................................................................................... 32 
12.0 
RISK ANALYSIS ................................................................................................................ 32 
12.1 
Anticipated Clinical Benefits ............................................................................................ 32 
12.2 
Foreseeable Adverse Events and Anticipated Adverse Device Effects ........................... 32 
12.3 
Risks Associated with Participation in Clinical Study....................................................... 33 
12.4 
Possible Interactions with Protocol-Required Concomitant Medications ......................... 33 
12.5 
Steps That Will be Taken to Control or Mitigate Risks .................................................... 34 
12.6 
Risk to Benefit Rationale ................................................................................................ 34 
APPENDIX I:  ABBREVIATIONS AND ACRONYMS .................................................................... 35 
APPENDIX II:  DEFINITIONS ........................................................................................................ 36 
REVISION HISTORY ..................................................................................................................... 40 
 
 
 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 6 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
 
COMPLIANCE STATEMENT  
 
This Study will be conducted in accordance with this Protocol, the Declaration of Helsinki, applicable 
Good Clinical Practices and applicable regulations and standards (e.g., US 21 CFR Parts 50, 56, 
812, and 820.30, US 45 CFR Part 46, ISO 14155:2020, and ISO 13485) and the appropriate local 
legislation(s).  
The most stringent requirements, guidelines or regulations must always be followed. The conduct of 
the study will be approved by the appropriate Review Board (IRB) of the respective sponsor locations 
and by the applicable regulatory authorities, when applicable. 
 
 
 
 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 7 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
INVESTIGATOR SIGNATURE PAGE 
I have read this Clinical Investigation Plan and agree to adhere to the requirements described in this 
plan, including but not restricted to the latest version of the Declaration of Helsinki, Good Clinical 
Practice, ISO 14155, Code of Federal Regulations Title 21, and applicable local, regional and 
national regulatory requirements.  
I will ensure that no study-specific tests or procedures will be undertaken prior to Institutional Review 
Board (IRB) approval and/or any other local, regional and national approvals have been obtained. 
Reporting requirements and conditions imposed by the relevant IRB will be observed and followed.  
Any participant enrolled in the study will be fully informed about the study objectives and scope and 
signed informed consent will be obtained before any study specific procedures are initiated.  
I will also ensure that all site staff under my supervision will be trained adequately about the study 
scope and requirements, and I will supervise the study conduct in accordance with above stated 
regulations.  
First Name: 
 
Last Name: 
 
Title: 
 
Signature: 
 
Date: 
          DDMMMYYYY
 
One copy for the Principal Investigator, one copy for iRhythm Technologies, Inc. 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 8 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
PROTOCOL SUMMARY 
 
Protocol Number  
IRT-003-2024 
Title 
Design Validation Study: Extended Wear Performance of the Zio 
monitor¹ 
Objective 
To evaluate the wear performance of the Zio monitor device in a 
representative population over an extended wear period (of up to 30 
continuous days) to demonstrate that the device can be worn with 
adequate patch adherence and signal quality through 21 days.  
Assessment of wear performance will include evaluation of the wear 
duration 
of 
the 
patch 
and 
percentage 
of 
analyzable 
electrocardiographic time.   
Product safety will be assessed by collection of all adverse events. 
Study Device 
Zio monitor 
Targeted Number of 
Participants  
A total of up to 75 participants will be enrolled at US locations. The 
study may enroll participants from the community surrounding San 
Francisco, CA and Deerfield, IL as referred by FieldWork® (or 
another recruitment vendor) at the iRhythm clinic in those 
locations.  
The study may also enroll participants from identified clinical 
locations at up to 3 additional health care institutions.    
Study Design 
A Prospective, multi-center, single-arm study to validate the design 
of the Zio monitor/Zio MCT device form factor in extended (21-day) 
wear. 
Performance 
Objectives and 
Measures  
Performance Objectives 
Mean wear duration and percent analyzable time of the Zio 
monitor will be assessed.  Performance goals include mean wear 
duration of 21 days and percent analyzable time of 80%.   
Performance objectives will be met if the mean wear duration is 
greater than 21 days, and percent analyzable time is greater than 
80% in 90% of subjects. 
 
Safety Measures 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 9 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
The proportion of participants that experience clinically significant 
skin irritation through 30 days of wear will be assessed through 
capture and reporting of all adverse events. 
Additional Device Measures 
 
Signal Artifact (%) – Defined as the proportion of ECG 
signal that is artifact over the wear duration, reported for 
each study device.  
 
Device Functionality (%)  – Defined as the proportion of Zio 
monitors recording a continuous ECG signal through 21 
days, and through 30 days. 
Other Measures 
Observational assessment of participant skin types that will be 
reported include: 
 
Participant Skin Type – Dry, Oily, Normal (Baseline only) 
 
Known Hyperhidrosis Status – Primary, Secondary or None 
(Baseline only) 
 
Fitzpatrick Skin Type (Baseline only) 
 
Chest Hair Density – e.g., smooth/no hair, some hair, 
moderately hairy, or very hairy (baseline and follow-up) in 
the target patch placement area 
Participant Visits 
On-location visits are planned for Baseline (time of patch 
application), 21 days, and 30 days following patch application. 
 
Telephone calls to the participants are planned for 7-day and 14-
day visits. 
Inclusion Criteria 
1. Participant must be 18 years or older at time of informed 
consent. 
2. Participant is willing and able to provide informed consent and 
be able to complete all visits for the study. 
Exclusion Criteria 
1. Participant has a known allergy to adhesives. 
2. Participant has a current skin infection or injury at location for 
study device placement. 
3. Participant is a member of a vulnerable population. 
4. Participant is a current or prior employee of iRhythm.  
5. Participant is unable or unwilling to participate or comply with 
study protocol. 
6. The local Investigator deems the participant has a condition that 
could limit the participant’s ability or willingness to participate in 
the study, or ability to comply with study required procedures 
and/or follow-up visits. 
7. Participant has experienced symptomatic episodes where 
instance variations in cardiac performance could result in 
immediate danger to the participant.
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 10 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
¹ The study device includes the wearable ECG adhesive assembly and symptom button common to both the Zio monitor and next 
generation Zio AT (Zio MCT) ambulatory cardiac monitoring devices.  The gateway associated with Zio MCT necessary for transmission 
of ECG data during device wear will not be included as part of this study.  For simplicity, the study device will be referred to Zio monitor 
within this protocol.  Additional information regarding the study device is included in Section 2.3. 
 
8. Participant has an external cardiac defibrillator or may be 
exposed to high frequency surgical equipment near strong 
magnetic fields or devices such as MRI during the wear period. 
9. Participant has a neuro-stimulator, as it may disrupt the quality 
of ECG data. 
10. Participant does not have the competency to wear the device for 
the prescribed monitoring period. 
11. Participant does not have the ability to consent for themselves 
(i.e., no LARs). 
Analysis 
Populations 
All analyses will be performed on the population of enrolled 
participants on whom the Zio monitor application was attempted.  
The age, sex at birth, and application type (HCP designee vs. self-
application) of participants will be monitored throughout the 
enrollment period to ensure representation across key user groups. 
 
Performance within subgroups including (but not limited to) sex at 
birth, age, and application type will be assessed. 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 11 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
1.0 
INTRODUCTION 
1.1 
Study Design 
This study is a prospective, multi-center, single-arm study to validate the design of the Zio® 
monitor2/Zio MCT® device form factor in extended (21-day) wear.  
1.2 
Study Objectives 
The objective of the study is to evaluate the wear performance of the Zio monitor device in a 
representative population over an extended wear period (of up to 30 continuous days) to 
demonstrate that the device can be worn with adequate patch adherence and signal quality through 
21 days. Assessment of wear performance will include evaluation of the wear duration of the patch 
and percentage of analyzable electrocardiographic time.  Product safety will be assessed by 
collection of all adverse events. 
2.0 
BACKGROUND AND RATIONALE 
Patients who are suspected of suffering from an arrhythmia-related condition typically undergo 
electrocardiography (ECG) monitoring.  Clinical symptoms associated with arrhythmia may include 
palpitations, shortness of breath, dizziness, lightheadedness, pre-syncope, syncope, or anxiety. 
Arrhythmias may also present asymptomatically.  Arrhythmias often occur infrequently and may not 
be detected with in-clinic 12-lead ECG monitoring (which records 10 seconds of data), or traditional 
ambulatory monitoring (i.e., with a Holter device up to 48 hours).  Long-term 14-day continuous 
ambulatory ECG monitoring is useful for the detection of infrequent arrhythmic events [1], though 
further extending the monitoring period may aid in detection of additional arrhythmias and provide 
additional clinical insights.  
The Zio monitor (K202359) received FDA 510(k) clearance on May 21, 2021 and is a long-term 
continuous ambulatory patch ECG monitor which adheres to the patient’s left pectoral region.  
Additional description of the device is provided in Table 1.  The Zio monitor is substantially equivalent 
to the predicate Zio XT device but is designed to be smaller and more than 50% lighter.   
The Zio monitor is breathable with a waterproof housing³, and a more flexible design for a secure 
attachment.  These refinements allow for a more comfortable wear experience [2] with longer wear 
times and, therefore, provide more complete diagnostic data [3].  
Like the predicate Zio XT device, Zio monitor is currently indicated for long-term continuous 
monitoring of up to 14 days.  However, successful performance verification testing at iRhythm has 
demonstrated that the Zio monitor is capable of recording continuous ECG data for up to 21 days. 
This extended wear clinical design validation study will assess the extended wear performance of 
the Zio monitor device, by having participants wear the device for as long as possible (up to 30 days) 
and recording their experience.   
 
 
²The study device includes the wearable ECG adhesive assembly and symptom button common to both the Zio monitor and next 
generation Zio AT  (Zio MCT) ambulatory cardiac monitoring devices.  The gateway associated with Zio MCT necessary for transmission 
of ECG data during device wear will not be included as part of this study.  For simplicity, the study device will be referred to Zio monitor 
within this protocol.  Additional information regarding the study device is included in Section 2.3. 
³The Zio monitor device should not be submerged in water. During a bath, keep the device above water. Please refer to the Zio monitor 
labeling instructions or Patient Guide for the full set of details. 
 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 12 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
Additionally, the percentage of analyzable ECG signal (i.e., percent analyzable time) will be 
assessed against a performance benchmark of 80%.  The device tested in this extended wear study 
will be the design cleared in K202359, with minor improvements for manufacturability and with the 
programming configurations updated to allow for continuous ECG data recording for up to 30 days.  
Performance objectives include a mean wear time of at least 21 days, and percent analyzable time 
(i.e., artifact-free ECG signal) greater than 80% for at least 90% of study participants. 
2.1 
Name of the Device 
The device to be tested is the modified Zio® monitor (iRhythm Technologies, Inc., San Francisco, 
CA), inventory part number DFG0001, or equivalent.   
2.2 
Intended Indication for Use 
The Zio monitor is a prescription-only, single-patient-use ECG monitor that continuously records 
data for up to 14 days. It is indicated for use on patients who may be asymptomatic or who may 
suffer from transient symptoms such as palpitations, shortness of breath, dizziness, lightheadedness, 
pre-syncope, syncope, fatigue or anxiety.   
In this extended wear clinical study, the Zio monitor is being evaluated in participants who will wear 
the device for up to 30 days, in order to achieve a mean wear time of greater than 21 days. 
2.3 
Description of the Device 
The Zio monitor is a non-sterile, single-patient-use ECG monitor and recorder that provides a 
continuous, single-channel recording, and is substantially equivalent to the predicate commercial Zio 
XT Patch (K121319).  The device is FDA cleared to be marketed commercially for recording of up 
to 14 days.  See “Table 1: Device Comparison” for additional details. The predicate Zio XT device 
has been the subject of extensive clinical study.  Findings have demonstrated improved diagnostic 
yield as compared to 24-48 Holter monitoring [4-7] and other ambulatory monitoring modalities [8]. 
The patch will be applied to the upper left pectoral region and activated by the study participants 
either in the clinic or at home, under the guidance of trained Study Staff.  Once activated, the Zio 
monitor records ECG data without patient interaction, with the goal of improving patient compliance 
via simplicity of operation.  There is a surface LED light that blinks to indicate proper activation and 
that the device is working or to indicate loss of connection with the skin or the presence of error 
conditions. 
When applied, the device provides continuous, single-channel ECG recording into memory without 
patient interaction for the duration of the prescribed monitoring. The Zio monitor features an 
embedded real-time clock (RTC) for reporting purposes.  The RTC is initialized at the manufacturing 
facility and requires no patient or user interaction.  ECG data are acquired via electrodes mounted 
on the underside – the skin contact side – of the patch.  Data are sampled with an analog/digital 
converter (ADC), and subsequently saved to the onboard memory.  Stored ECG data are recorded 
into non-volatile memory, so data will not be lost in the event of power supply failure or battery expiry.  
There is a button on the surface of the patch, which may be pressed by the patient to indicate when 
he or she is experiencing a symptom. This button press is logged by software into a secondary data 
stream, where event time is noted. Recording continues without interruption. 
During normal operation, the device dynamically adjusts the input signal gain to a level that will 
maximize usage of ADC dynamic range and improve digital resolution of the recorded ECG signal, 
thereby improving the fidelity and contributing to improved interpretation results, particularly in 
situations of low-amplitude input signals. 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 13 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
At the conclusion of the wear period, the participant will remove the patch using the supplied 
materials and return it to the Sponsor. Once received, the recorded data will be downloaded for 
analysis by the Sponsor. The recorded ECG data are processed for detection of arrhythmias using 
an FDA-cleared (K222389) set of artificial intelligence algorithms [9] combined with trained cardiac 
technician review to generate a preliminary report describing rhythm findings.   
Table 1: Device Comparison (Substantial Equivalence Summary) 
Feature 
Predicate Commercial Device: 
Zio® XT Patch (K121319) 
Study Device: 
Zio® monitor (K202359) 
Indications for Use 
Indications for Use Statements 
The Zio® Patch is a prescription-only, single-
patient-use, 
continuously 
recording 
ECG 
monitor that can be worn up to 14 days. It is 
indicated for use on patients who may be 
asymptomatic or who may suffer from 
transient symptoms such as palpitations, 
shortness 
of 
breath, 
dizziness, 
light-
headedness, presyncope, syncope, fatigue, or 
anxiety. 
The Zio® monitor is a prescription-only, single-
patient-use ECG monitor that continuously records 
data for up to 14 days. It is indicated for use on 
patients who may be asymptomatic or who 
may suffer from transient symptoms such as 
palpitations, shortness of breath, dizziness, 
lightheadedness, pre-syncope, syncope, fatigue or 
anxiety. 
General Characteristics  
Classification 
Class II:  21CFR870.2800
Same
Product Code 
DSH
Same
Patient Environment 
Ambulatory 
Same 
Patient Population 
Non-pediatric, non-critical care patients 
Same 
Programmed ECG Storage 
Duration  
14 days 
Up to 30 days 
Technological Characteristics  
Event Trigger 
Manually by patient 
Same 
Size 
The Zio Monitor has a reduced form factor 
Performance Characteristics  
 
Weight 
24.7 g 
10.0 g 
Dimensions 
5.2 x 2.0 x 0.5 in 
5.5 x 2.2 x 0.4 in 
Photograph or Drawing 
 
 
 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 14 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
Feature 
Predicate Commercial Device: 
Zio® XT Patch (K121319) 
Study Device: 
Zio® monitor (K202359) 
Zio XT (K121319) 
Zio® monitor (K202359) 
 
In addition to the Zio monitor and Zio XT long-term continuous ambulatory ECG monitors, a mobile 
cardiac telemetry device, Zio® MCT, is currently in development.  Zio MCT will leverage the same 
patch ECG form factor and end-of-wear ECG review as Zio monitor, but also enables transmission 
and review of symptomatic or auto-triggered events during the wear period.  Zio MCT-specific 
features, including auto-detection and event transmission during wear will not be enabled nor 
evaluated as part of this study.  However, this assessment of extended wear performance is 
applicable to both Zio monitor and Zio MCT as the patch devices share the identical electrical, 
mechanical, and adhesive assembly.  The main difference in the patch design is the firmware and 
the activation of the Bluetooth communication to the Gateway.  This is not expected to impact wear 
duration on Zio MCT as it is not adding weight or changing adhesive area vs Zio Monitor. 
The gateway which enables transmissions will not be included in this study. 
2.4 
Number of Participants 
A total of up to 75 participants will be enrolled in this study.  
2.5 
Overall Flow of the Study and Follow-up Schedule 
Figure 1 shows the overall flow of the study.  Participants who meet all inclusion and none of the 
exclusion criteria are eligible for enrollment into the study.  Study visits will be performed in-clinic 
(Baseline, 21 day and 30 day) and by telephone (7 and 14 day).   
Participants must read, understand, and sign (by hand or electronically) the study Informed Consent 
Form prior to the initiation of the baseline assessment visit and start of device wear.  Once consented, 
participants will have a study device applied to their chest by a study staff member, or be provided 
a study device to self-apply at home or on-site.  Study devices must be applied no later than the 
expiration date indicated on the kit.  Participants will be considered enrolled after they have signed 
the Informed Consent Form and attempted patch application has occurred.  Attempted patch 
application is defined as the opening of the patch kit and initiation of the shaving step necessary for 
skin preparation. 
During the wear period, participants will be contacted by phone to determine adverse events and 
remind them of their next visit. Enrolled participants will undergo clinical evaluation at baseline and 
21 days and 30 days after on-site or at-home patch application. They will also be provided a contact 
number to report any adverse events that occur between planned visits. 
 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 15 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
 
 
Important Notes: 
1. 
Participants will be considered enrolled after they have signed the Informed Consent Form and have 
attempted to apply the patch.   
2. 
Follow-up visits are conducted at the indicated days following application of the patch, whether in 
clinic or by phone. 
3. 
Early patch detachment and/or completion of the 30-day visit also includes a study completion form. 
Candidate Participant 
Meets All Inclusion and  
No Exclusion Criteria? 
Participant does not 
qualify for the study 
30-Day Follow-Up Visit (+ 3 days) 
•
Assess device condition 
•
Assess for any Adverse Event 
•
Remove device 
•
Skin Assessment
Device Analysis 
•
ECG data from device are downloaded for endpoint analyses
21-Day Follow-Up Visit (+ 3 days) 
•
Assess device condition 
•
Assess for any Adverse Event 
•
Schedule final visit 
14-Day Follow-Up Phone Visit (+ 3 days) 
•
Assess device condition 
•
Assess for any Adverse Event 
•
Remind of next visit
7-Day Follow-Up Phone Visit (+ 3 days) 
•
Assess device condition 
•
Assess for any Adverse Event 
Baseline Visit 
•
Eligibility is confirmed 
•
Participant reviews and signs the Consent Form after all 
questions are answered 
•
Baseline assessments 
•
Device is applied to begin study device wear 
Figure 1: Overall Study Flow 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 16 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
2.5.1 
Study Safety Committee 
A study safety committee will meet as needed to assess any safety events that may occur.  The 
study safety committee meetings will be conducted according to a separate charter.  The charter will 
include meeting scope, roles and activity specifics. 
3.0 
STUDY PERFORMANCE OBJECTIVES AND ADDITIONAL MEASURES 
3.1 
Wear Time Performance Objective 
Wear duration is defined as the number of days the patch is attached to the participant.  Wear 
duration measurement will start at the time of device application and will end at any of the following 
events: 
 
the device is removed at the 30-day follow-up visit, or 
 
the device fails to adequately adhere to the skin 
All enrolled participants on whom patch application was attempted will be included as part of the 
mean wear duration analysis. However, participants who discontinue wear of the device for 
reasons outside of the study protocol, or occurrence of an adverse event not related to the study, 
will not be counted in the analysis. Full disclosure for reasons of discontinuation will be provided in 
the study report. 
Mean wear duration will be compared to a performance goal of 21 days. The performance 
objectives will be met if the mean wear duration is greater than 21 days. 
3.2 
Analyzable Time Performance Objective 
Analyzable time is the percentage of time during the wear of the Zio monitor device which yields 
analyzable ECG signal (i.e., free from signal artifact).   
All enrolled participants in whom patch application was attempted will be included as part of the 
percent analyzable time analysis. However, participants who discontinue wear of the device for 
reasons outside of the study protocol, or occurrence of an adverse event not related to the study, 
will not be counted in the analysis. Full disclosure for reasons of discontinuation will be provided in 
the study report. 
Percent analyzable time will be compared to a performance objective of 80%. The performance 
objective will be met if the percent analyzable time is greater than 80% in 90% of subjects.  
3.3 
Safety Measures 
All enrolled participants on whom patch application was attempted will be included in the safety 
analysis.  The proportion of participants that experience clinically significant skin irritation through 
30 days of wear will be assessed. 
 
 
Reaction severity will be assessed and reported, as follows [10]: 
o Weak Positive Reaction:  Presence of erythema infiltration, discrete papules 
o Strong Positive Reaction:  Presence of erythema infiltration, papules, discrete 
vesicles 
o Extreme Positive Reaction:  Presence of bullous or ulcerative reaction, coalescing 
vesicles 
An ‘Extreme Positive Reaction’ will be considered a clinically significant skin irritation. 
Any skin reaction should be reported as an adverse event. 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 17 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
3.4 
Additional Device Measures 
 
Signal Artifact (%) – Defined as the proportion of ECG signal that is artifact over the wear 
duration, reported for each study device 
 
Device Functionality (%) – Defined as the proportion of Zio monitors recording a continuous 
ECG signal for (1) 21 days, and (2) for 30 days  
3.5 
Other Measures 
Observational assessment⁸ of participant skin types that will be reported include: 
 
Participant Skin Type – Dry, Oily, Normal (Baseline only) 
 
Known Hyperhidrosis Status – Primary, Secondary or None (Baseline only) 
 
Fitzpatrick Skin Type -Type I-VI (Baseline only) 
 
Chest Hair Density – e.g., smooth/no hair, some hair, moderately hairy, or very hairy 
(baseline and follow-up) in the target patch placement area 
4.0 
PARTICIPANT SELECTION AND WITHDRAWAL  
4.1 
Participant Recruitment Population and Retention 
A study population representative of the intended population and who meet the study eligibility 
criteria will be approached for participation.  iRhythm may utilize a recruitment firm such as 
FieldWorks® or community clinics who are qualified by experience and able to support this study.  
The clinics and FieldWorks may utilize email solicitation, social media posting, review of their current 
research database of potential participants and/or flyer posting with prior approval by the IRB.  
Recruitment of at least 61 participants will be needed, and enrollment may continue up to a total of 
75 participants.  
To ensure recruitment of a population representative of patients undergoing long-term continuous 
monitoring, age, gender, and in-clinic (HCP designee) vs. self-application will be tracked by the study 
team. The following represent enrollment targets across these key groups: 
 
Approximately 1/3 of participants ≥51 and <70 years of age 
 
Approximately 1/3 of participants ≥70 years of age 
 
At least 40% of participants should be female 
 
Devices are self-applied for approximately 1/3 of the study population  
4.2 
Participant Screening and Informed Consent 
Participant screening and informed consent may be performed in-person, by telephone, or by 
videotelephony (e.g., Zoom).   
⁸See Appendix II for assessment definitions. 
4.2.1 
Participant Screening 
A recruitment firm may be utilized for initial screening. Participants who have been identified by the 
recruitment firm will be seen at one of two Sponsor locations (San Francisco, CA or Deerfield, IL), 
the investigator or research staff, who have been trained to the Protocol, will verify all participants 
meet all inclusion and no exclusion criteria to determine if the potential participant is eligible for study 
enrollment.   
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 18 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
Community clinics who have been identified, selected, trained and have provided all appropriate 
documentation for the study may also be utilized for screening and enrollment. The participants from 
this group may be clinically indicated for a Zio monitor prescription and willing to wear the Zio for an 
extended period of time.  
In both cases, potential participants will be assigned a screening number (assigned 
sequentially/chronologically).  An accurate and up-to-date screening log of all participants 
considered for the trial will be maintained at each study location.  The result of the participant 
screening process shall be documented in the screening log to include presentation route, whether 
the participant met eligibility criteria (and if not, which eligibility criteria were not met), and whether 
the participant was subsequently enrolled.   
4.2.2 
Informed Consent 
The Study and the Study Informed Consent Form (ICF) must receive approval by an independent 
IRB prior to beginning enrollment into the Study. The central IRB for this study is Advarra. 
During the informed consent process, the investigator or designee, who has been trained on the 
Protocol, will explain the nature and scope of the trial, potential risks and benefits of participation, 
and answer questions from potential participants.   
All participants must sign and date the IRB-approved informed consent form prior to any trial-specific 
procedures.  Those who are not able to provide consent on their own will not be enrolled.  Obtaining 
the consent, provision of copy to the participant, along with date and time must be documented in 
the participant’s source documents.  
The informed consent form must also be signed by the investigator or designee. The investigator or 
designee is responsible for advising the participant of any new information about the study or the 
study device(s) that may become known during the study.  The consent may be administered by 
paper or through the use of an electronic consent form. 
An authorization for use and disclosure of the participant’s protected health information, in 
accordance with the Health Insurance Portability and Accountability Act (HIPAA), must be obtained 
from the participant. The requirements of HIPAA elements may be incorporated into the Informed 
Consent Form or it may exist as a standalone document 
4.2.3 
Disclosure of Participant Personal Contact Information 
In order to conduct a phone visit with the participant, the study team at iRhythm may collect the 
participant’s phone number and email.  The participant’s identity will be anonymized to the extent 
possible.  Only those iRhythm study staff individuals who are directly involved with the study will 
have access to the participant’s PHI for those individuals enrolled through the iRhythm clinics.  
Participants enrolled in the community clinics will have their information pseudo anonymized and 
only the community clinic study staff will have access to their full information. 
4.3 
Eligibility Criteria 
Participants shall be screened per the criteria listed below.  Assessment for eligibility criteria will be 
completed through an interview with a potential participant. Participants must meet ALL of the 
inclusion criteria to be considered for the study. If ANY of the exclusion criteria are met, the 
participant is excluded from the study.  Participants meeting these criteria will be approached to 
provide informed consent for participation in the Study and included on the screening log. 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 19 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
4.3.1 
Inclusion Criteria 
Participants must meet all of the following inclusion criteria in order to participate in the study: 
1. Participant must be 18 years or older at time of informed consent.  
2. Participant is willing and able to provide informed consent and able to complete all visits for 
this study. 
4.3.2 
Exclusion Criteria 
Participants who meet any of the following exclusion criteria may not participate in the study: 
1. Participant has a known allergy to adhesives. 
2. Participant has a current skin infection or injury at location for study device placement. 
3. Participant is a member of a vulnerable population. 
4. Participant is a current or prior employee of iRhythm. 
5. Participant is unable or unwilling to participate or comply with study protocol. 
6. The local Investigator deems the participant has a condition that could limit their ability or 
willingness to participate in the study, or ability to comply with study required procedures 
and/or follow-up visits. 
7. Participant has experienced symptomatic episodes where instance variations in cardiac 
performance could result in immediate danger to the participant. 
8. Participant has an external cardiac defibrillator or may be exposed to high frequency surgical 
equipment near strong magnetic fields or devices such as MRI during the wear period. 
9. Participant has a neuro-stimulator, as it may disrupt the quality of ECG data. 
10. Participant does not have the competency to wear the device for the prescribed monitoring 
period. 
11. Participant does not have the ability to consent for themselves (i.e., no LARs). 
4.4 
Participant Enrollment and Inclusion  
Participants are considered enrolled after they have signed the Informed Consent Form and patch 
application has been attempted.  Attempted patch application is defined as the opening of the Patch 
kit and initiation of the first step necessary for skin preparation. 
Enrolled participants on whom patch application is attempted will be included in the analysis 
population. Consistent with recent FDA guidance on increasing diversity in clinical trial enrollment 
(Enhancing the Diversity of Clinical Trial Populations – Eligibility Criteria, Enrollment Practices, and 
Trial Designs:  Guidance for Industry, Issued November 2020), iRhythm will attempt to implement 
measures to ensure that the study population reflects the characteristics of clinically relevant 
population. Section 4.1 above describes measures taken to ensure enrollment of a relevant 
population with respect to age, sex and device application (in clinic or self-application).   
In addition, diversity across races and ethnic groups will be considered in selection of study sites 
and through recruitment activities. The study intends to enroll a diverse group of participants 
representative of the US population at large. 
4.5 
Participant Payment  
Participants who meet eligibility and are enrolled in the study may be eligible to receive a stipend.  
In the event that the recruiting firm was utilized for the participant enrolled, the firm will manage all 
activities for payments including reporting of the payments to the Internal Revenue Service if 
required.  
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 20 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
For those participants enrolled in the study through the clinical study site, stipends may also be 
included. However, the device is considered to be used in a clinical care setting and will be provided 
at no charge to the participant; the full study report will be provided to the ordering investigator at 
the conclusion of the wear time. No submission to the participant’s insurance should be made for 
this portion of the visit. 
For those participants enrolled through the recruitment firm to the iRhythm clinics payment for 
participation, parking, travel, etc. will be managed by the recruitment firm.  
The amount of the participant stipend will be included in the Informed Consent form and approved 
by the IRB.   
4.6 
Participant Discontinuation 
Participants shall remain in the study until completion of the required follow-up period, unless the 
device experiences early detachment. The participant’s involvement in any clinical study is voluntary 
and the participant has the right to withdraw at any time without penalty or loss of benefit. 
Conceivable reasons for discontinuation may include, but are not limited to, the following: 
 
Participant death 
 
Participant voluntary withdrawal  
 
Participant withdrawal by physician as clinically-indicated 
 
Participant lost-to follow-up as described below  
The Sponsor study staff must be notified of the reason(s) for participant discontinuation. Study staff 
are required to report this to the central IRB as defined by the IRB’s requirements.  
No additional follow-up will be required or data recorded from participants once withdrawn, except 
for the status (deceased/alive). 
4.6.1 Lost-to-Follow-up: 
If the participant misses the scheduled follow-up time point and the attempts at contacting the 
participant detailed below are unsuccessful, then the participant is considered lost to follow-up. Study 
personnel shall make all reasonable efforts to locate and communicate with the participant (and 
document these efforts in the source documents), including the following, at each contact time point: 
 
A minimum of 2 telephone calls or emails on different days over a 10-day period to contact 
the participant should be recorded in the source documentation, including date, time and 
initials of study personnel trying to make contact. 
 
If these attempts are unsuccessful, a certified letter should be sent to the participant.  The 
letter will request the participant to contact the investigator. Study staff will also request return 
of the Zio to iRhythm as soon as possible.  
4.7 
Number of Participants Required to be Included in the Study 
A total of up to 75 participants will be included in the study. 
4.8 
Estimated Time Needed to Enroll this Number  
It is anticipated that it may take up to 8 weeks to enroll all required participants.   
4.9 
Expected Duration of Each Participant’s Role 
The expected duration of participation is approximately 30 days.   
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 21 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
4.10 
Total Expected Duration of the Study 
The time to complete the Study is estimated to be approximately four months (two months to 
complete participant enrollment, one month follow-up and one month to complete analysis and 
generate the study report).   
4.11 
Study Completion 
A participant is considered to have completed the study when any of the following has occurred: 
 
The participant is considered lost to follow-up per the above definition  
 
The participant withdraws consent 
 
The investigator withdraws the participant from the Study  
 
The participant has died  
 
The Study has been completed (e.g., the participant’s 30-day or final follow-up time point has 
been reached)  
 
The patch has prematurely detached from the participant (in the case of early detachment 
the participant should notify study staff of the date and time of detachment, and a study 
completion visit will be scheduled).      
 
The Sponsor has terminated the Study 
Sponsor must be notified of the reason for participant discontinuation.  Investigators must also report 
this to their IRB, as required. Participants will not be replaced. 
5.0 
BASELINE VISIT AND FOLLOW-UP ASSESSMENTS 
5.1 
Baseline (Visit 1) 
During the baseline visit (visit 1) the participant will be consented and the consent documented prior 
to patch application additional activities include: 
Baseline health and demographic information: 
The following information will be gathered from each participant in order to establish representation 
of the population and includes minimum:  
 
Medical Background/History, including:  
­ Cardiac Disease History 
 
Including indication for monitoring if enrolled at a clinical care site 
­ Skin characteristics as reported by the participant 
 
Skin Type (e.g., dry, oily, or normal) 
 
Hyperhidrosis Status (e.g., primary, secondary, or none – see definitions in 
appendix ) 
 
Fitzpatrick Skin Type (e.g., Type I-VI) – using the Fitzpatrick Skin Type 
assessment questionnaire completed by the participant 
 
Chest Hair Density by visual inspection (e.g., smooth/no hair, some hair, 
moderately hairy, or very hairy) in the target patch placement area 
­ List of current medications 
 
Demographic Information 
 
­ 
Age 
­ 
Sex at birth 
­ 
Race 
­ 
Ethnicity 
­ 
Weight 
­ 
Height 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 22 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
 
 
Patch application: 
The Zio monitor will be applied to the participant’s left upper chest/pectoral region and may be 
completed by either the participant (self-application) or by a Health Care Provider (HCP) or designee 
(i.e. the study coordinator or cardiac technician). The application process for this study will be 
conducted as outlined in the Zio Monitor Instructions for Use – LB10117.01. 
During the baseline visit, participants will either have a patch applied by a HCP designee or study 
staff member or participants will self-apply the patch. In the event of self-application, the study 
participant will open the Zio monitor kit and the Zio monitor Instructions for Use and will self-apply 
the device in the presence of a study staff member. The study staff member is allowed to provide 
some guidance, but every effort should be made to allow the participant to place the patch without 
intervention for the study staff. 
If external community clinic sites are utilized the patch can be applied in the standard method for the 
site. 
5.2 
Patch Wear Period 
All consented participants in whom the Zio monitor Patch application is attempted will be considered 
enrolled in the study.  Patch application is considered to have been attempted when the Zio monitor 
Patch kit is opened and the first step necessary for skin preparation has been initiated.  The 
participant will be instructed to wear the device for as long as possible, up to the 30-day visit.   
Study participants will be instructed to press and hold along the edges of the patch if they notice the 
patch peeling or lifting at the edges during the wear period.  If a patch completely detaches from the 
participant’s chest, the patch will not be re-applied.  In the case of early patch detachment, the 
participant should notify study staff of the date and time of detachment, and a study completion visit 
should be scheduled as soon as possible.      
At any time after patch application, if the device is determined to no longer be functioning (for 
example, if a rapidly blinking orange light is observed), the device will not be replaced.  The date 
and time the determination of function failure will be noted as close to accurate as possible. As a 
non-functioning device does not present a safety concern, the participant will be asked to continue 
wearing the non-functioning patch for as long as possible, in order to record wear duration and wear 
experience data.   
5.3 
Protocol Required Medications 
There are no protocol required medications for this study, and no medications will be administered 
for the study. A complete list of current medications will be requested during the baseline visit. 
Updates to the list may be made if there is a change in the medication regime during the time of 
participation. 
5.4 
7-Day and 14-Day (+ 3 days) Participant (Phone Call Visit 2 & 3) 
A phone call at days 7 and 14 will be conducted in order to assess the status of the participant and 
the patch adherence.  
5.5 
21-Day (+3 days) Participant Follow-up (Visit 4) 
At day 21 following patch application and up to day 24, participants will be asked to return to the 
clinic and the following activities will be conducted: 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 23 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
- 
Skin assessment by HCP or designee, including photograph of the area 
- 
Adverse Event review 
- 
Answering of any questions and verification of ongoing consent to study participation  
5.6 
30-Day (±3 days) Participant Follow-up (Visit 5) 
At day 30 following patch application and up to day 33, participants will be asked to return to the 
clinic and the following activities will be conducted: 
- 
Skin assessment by HCP or designee, including photograph of the area 
- 
Adverse Event review 
- 
Zio patch removal and visual inspection 
- 
Patch return to iRhythm Technologies, Inc. 
Participants who applied the Zio to themselves at the Baseline visit will be asked to remove the patch. 
They may ask a Study Staff member to provide guidance in the removal process.  
Study clinical assessments and activities are summarized in Table 2. 
 
 
This area intentionally left blank 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 24 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
Table 2: Clinical Assessment Schedule 
Required Assessments to be Collected 
Baseline 
(Visit 1) 
7 & 14-Day 
(Visit 2 & 3) 
21-Day2 
(Visit 4) 
30-Day2 
(Visit 5) 
±3 days 
Phone Call 
only 
+3 days 
+3 days  
Informed Consent1 
X 
X 
- 
- 
Medical and Cardiac Background/History 
X 
- 
- 
- 
Fitzpatrick Skin Assessment 
X 
- 
- 
- 
Skin Condition Assessment2 
X 
- 
X 
X 
Assessment of Device Adhesion 
Performance, Including photograph 
- 
- 
X 
X 
Adverse Events3 
X4 
X 
X 
X 
1. Continued Informed Consent will be verified at each post-baseline contact.  
2. Including chest hair density, as applicable. 
3. Adverse Events include serious adverse events, all device-related complications, device 
deficiencies, device malfunctions, procedures and any hospitalizations.  
4. AEs are only assessed following Informed Consent and participant enrollment into the study. 
 
The study device will be returned to iRhythm Technologies, Inc. for download and analysis of the 
ECG signal collected during the wear.   
Upon completion of study follow-up, all devices will be retrieved from study participants and returned 
to the Sponsor for analysis. Those devices that were applied to participants in the community clinic 
setting will be processed through the algorithm and reviewed by the clinical research qualified 
cardiac technicians, the preliminary report will be provided to the Investigator at the clinic consistent 
with iRhythm Technologies, Inc. standard process. It will be up to the Investigator or HCP at that 
location for any needed clinical decision making. 
For those devices that were applied to participants from the recruitment firm and enrolled at an 
iRhythm location will also be processed through the algorithm and reviewed by a clinical research 
qualified technician. The preliminary report will be provided to a Safety Committee and reviewed by 
a licensed cardiologist for finalization and determination of any diagnosis. A copy of the report will 
also be provided to the participant for their records and to share with their personal physicians. 
6.0 
ADVERSE EVENTS 
Adverse events will be monitored and reviewed with the Study Investigator to determine any 
necessary action.  To comply with standards and guidelines on clinical study adverse event reporting, 
the following standard definitions and reporting timelines will be adhered to for this study.  
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 25 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
6.1 
Definitions 
6.1.1 
Adverse Event 
An adverse event (AE) is any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in participants, users or other 
persons, whether or not related to the medical device. For those participants enrolled at the 
community clinic locations it is anticipated that arrhythmias will be noted on the scans. These are 
not considered adverse events and do not require reporting unless they have caused an adverse 
event (i.e., rapid atrial fibrillation is noted on scan, during this time the subject had a syncopal episode 
that resulted in bruising. The atrial fibrillation is not the AE but the syncopal episode is an AE and 
must be reported). 
For this study AEs will be defined as follows:  
 
Mild:  Transient or mild discomfort; no limitation in activity; no medical intervention/therapy 
required. 
 
Moderate:  Mild-to-moderate limitation in activity, some assistance may be needed; no or 
minimal medical intervention/therapy required. 
 
Severe:  Marked limitation in activity, some assistance usually required; medical 
intervention/therapy required, hospitalizations possible. 
 
Life-threatening:  Extreme limitation in activity, significant assistance required; significant 
medical intervention/therapy required hospitalization or hospice care probable. 
6.1.2 
Serious Adverse Event 
If the AE meets any of the criteria below, it is regarded as a serious adverse event (SAE) and is 
required to be reported according to the FDA guidelines for SAE reporting.  
a) Led to a death, 
b) Led to a serious deterioration in health that either: 
1) Resulted in a life-threatening illness or injury, or 
2) Resulted in a permanent impairment of a body structure or a body function, or 
3) Required in-patient hospitalization or prolongation of existing hospitalization, or 
4) Resulted in medical or surgical intervention to prevent life threatening illness or injury or 
permanent impairment to a body structure or a body function. 
c) Led to fetal distress, fetal death or a congenital abnormality or birth defect. 
An important medical event that may not result in death, be life-threatening, or require hospitalization 
but may be considered serious when, based upon appropriate medical judgment, may jeopardize 
the participant and/or may require intervention to prevent one of the outcomes listed in this definition 
may also be considered an SAE. 
Note 1: This includes device deficiencies that might have led to a serious adverse event if a) suitable 
action had not been taken or b) intervention had not been made or c) if circumstances had been less 
fortunate. These are handled under the SAE reporting system. 
Note 2: A planned hospitalization for pre-existing condition, or a procedure required by the Clinical 
Protocol, without a serious deterioration in health, is not considered to be a serious adverse event. 
6.1.3 
Device Malfunction 
A device malfunction (DM) is the failure of a device to meet its performance specifications or 
otherwise perform as intended, when used in accordance with the IFU or protocol. 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 26 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
6.2 
Device Relationship 
Determination of whether there is a reasonable possibility that a product or device caused or 
contributed to an AE is to be determined by a study staff and recorded on the appropriate CRF. 
Determination should be based on assessment of temporal relationships, evidence of alternative 
etiology, medical/biologic plausibility, and patient condition (pre-existing condition). 
6.2.1 
Unanticipated (Serious Adverse) Device Effect [U(S)ADE] 
Unanticipated serious adverse device effect (USADE) refers to any serious adverse effect on health 
or safety or any life-threatening problem or death caused by, or associated with, a device, if that 
effect, problem, or death was not previously identified in nature, severity, or degree of incidence in 
the protocol or application (including a supplementary plan or application), or any other unanticipated 
serious problem associated with a device that relates to the rights, safety, or welfare of participants.  
See Anticipated Device Effects (Section 12.2). 
6.3 
Adverse Event/Device Deficiency/Product Experience Reporting 
6.3.1 
Adverse Event Reporting  
Occurrences of adverse events will be monitored for each participant during the course of the study 
as required by this protocol, per AE and SAE definitions as noted in the sections above. 
All information must be entered in the Electronic Data Capture (EDC) system as soon as feasible. 
AEs need to be collected for consented participants on the appropriate AE CRF. Additional 
information with regards to an adverse event should be updated within the appropriate CRF and 
source records. 
Serious adverse events (SAEs) that occurred in the user or persons other than the study participant 
should not be entered in the CRF; they should be reported to researchstudies@irhythmtech.com.  
Study staff will regularly monitor this email address and will investigate all events reported.  
The investigator will report all SAEs to the Sponsor as soon as possible but no later than 3 calendar 
days from the day the study personnel became aware of the event or as per the investigative 
location’s local requirements, if the requirement is more stringent than those outlined. The date the 
study staff became aware that the event met the criteria of a serious adverse event must be recorded 
in the source document. The Investigator will further report the SAE to the local IRB according to 
reporting requirements. 
6.3.2 
Unanticipated Serious Adverse Device Effect Reporting 
iRhythm (the Sponsor) is required to report and document any USADE as soon as possible, but at 
least within 24 hours of the Investigator’s knowledge of the event.  
6.3.3 
Device Deficiency/Device Malfunction Reporting 
All device deficiencies/malfunctions should be reported on the appropriate CRF no later than 3 
calendar days from the day the study personnel became aware of the event or as per the 
investigative location’s local requirements, if the requirement is more stringent than those outlined. 
An email address (researchstudies@irhythmtech.com) will be made available to allow the 
investigator to report device deficiencies/malfunctions. This does not replace the CRF. All 
information must still be entered in the CRF as soon as feasible.  Study staff will regularly monitor 
this email address and will investigate all events reported.  
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 27 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
In case a device deficiency/malfunction occurred before the patient ID has been assigned, the device 
deficiency should also be reported to iRhythm via researchstudies@irhythmtech.com.  
The device, if not applied or not remaining on the participant, should be returned to iRhythm 
Technologies, Inc. 
Device deficiencies/malfunctions should be reported to the IRB per the investigative location’s local 
requirements and IRB requirements. 
6.3.4 
Adverse Event Reporting to Country Regulatory Authorities by the Sponsor 
Where required by local or regional requirements, the Sponsor will report the SAEs and DDs to the 
appropriate regulatory authority.  
7.0 
STATISTICAL ANALYSIS 
7.1 
Analysis Population 
All analyses will be performed on the population of enrolled participants in whom patch application 
was attempted. 
7.2 
Sample Size Calculations and Assumptions 
A prior study of 30 subjects instructed to wear the Zio monitor device up to 30 days resulted in a 
mean wear time of >24 days (24.9 ± 9.3 days).  
Therefore, a power analysis was performed using the following assumptions: 
 
Performance goal:  > 21 days 
 
Estimated wear duration with the Zio monitor patch:  24.0 days 
 
Estimated standard deviation of wear duration with the Zio monitor patch:  9.3 days 
 
Statistical test:  One sample t-test 
 
Statistical Power:  80% 
 
Significance level:  One-sided alpha = 0.05 
Given these assumptions, enrollment of 61 participants is required to assess performance of wear 
duration performance.   
SAS Enterprise Guide 8.3 was used for all calculations.  
In order to assess the frequency of adverse events with reasonable precision, and to account for the 
possibility that up to 25% of enrolled participants may not provide ECG data at the 30-day visit due 
to device removal or loss to follow-up, enrollment of up to 75 participants is planned. 
7.3 
Planned Interim Analyses 
There is no planned interim analysis for this study.  
7.4 
Statistical Analyses 
For wear duration performance, mean wear duration, standard deviation and 95% confidence 
interval will be reported.  For analyzable time performance, the mean percent analyzable time, 
standard deviation, 95% confidence interval, and percentage of patients with analyzable time 
>80% will be reported.  Performance objectives will be met if the mean wear duration is greater 
than 21 days, and percent analyzable time is greater than 80% in 90% of subjects. 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 28 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
For other analyses, mean and standard deviation or median, interquartile range, minimum and 
maximum will be reported for continuous variables; counts and percentages will be reported for 
categorical variables. 
7.4.1 
Subgroup Analysis 
Performance within subgroups including (but not limited to) sex, age, and application method (in-
clinic HCP or designee vs. self-applied) will be assessed.  
8.0 
QUALITY CONTROL AND QUALITY ASSURANCE 
8.1 
Selection of Study Site Locations and Investigators 
iRhythm Technologies, Inc. will utilize two iRhythm locations for the recruitment firm’s referrals and 
participant enrollment. The locations will ensure study staff at their locations are trained appropriately. 
Contract Study Coordinators may be utilized at these locations to decrease any biases. The primary 
investigator of the study will also serve as the Principal Investigator at the iRhythm locations. 
Community Clinic Study centers will be selected based on qualifications of the center. At a minimum, 
they will have an investigator who has experience in clinical research, has staffing to meet the needs 
of the study, has adequate population to recruit for the study and has passed the qualification 
process conducted by iRhythm’s study management team. 
Prior to receipt of study devices all locations must be trained to the protocol, the CRFs, and other 
appropriate study activities. For community clinic study centers they must also have a contract in 
place specific to this study. All centers and locations MUST have IRB approval to recruit and enroll 
participants. 
Good Clinical Practice certification is required for all study staff who will have direct contact with the 
study participants or their data. 
8.2 
Protocol Amendments 
The Sponsor will provide approved Protocol amendments to the Investigator(s) prior to implementing 
the amendment. The Principal Investigator is responsible for notifying the IRB or equivalent 
committee of the Protocol amendment (administrative changes) or obtaining IRB’s approval of the 
Protocol amendment (changes in participant care or safety), according to the instructions provided 
by the Sponsor with the Protocol amendment.   
Acknowledgement/approval by the IRB of the Protocol amendment must be documented in writing 
prior to implementation of the Protocol amendment. Copies of this documentation must also be 
provided to iRhythm Technologies, Inc. 
8.3 
Training 
8.3.1 
Study Training 
All Investigators/study personnel, designee, etc. are required to attend the study training sessions, 
which may be conducted at a sponsor location initiation visit (SIV) or other appropriate training 
sessions. Over-the-phone, ‘webinar’, or self-training to the study and/or the device may take place 
as needed. Training of Investigators/study personnel will include, but is not limited to, the Protocol 
requirements, device usage, electronic CRF completion and study personnel responsibilities.  
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 29 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
All Investigators/study personnel that are trained must sign a training log (or an equivalent) upon 
completion of the training. Prior to signing the training log, Investigator/study personnel must not 
perform any study-related activities that are not considered standard of care at the sponsor location. 
All study personnel who has been trained to the study must also be listed on the Delegation of 
Authority log provided by iRhythm. The log must be kept updated throughout the study. A final copy 
of the DOA log will be collected from each study center and location for filing in the TMF for the study.  
8.3.2 
Training of Sponsor’s Monitors 
Sponsor and/or designated study monitors will be trained to the Protocol, case report forms and 
device usage (as appropriate). Documentation of this training will be according to written procedures. 
8.4 
Monitoring 
Centralized monitoring will occur through routine internal data review. This monitoring is designed 
to identify missing and inconsistent data, data outliers, and potential Protocol deviations that may be 
indicative of non-compliance at the sponsor location. On-site monitoring may occur at the discretion 
of the Sponsor. 
Prior to initiating any procedure, the Sponsor monitor (or delegate) will ensure that the following 
criteria are met: 
 
The investigator understands and accepts the obligation to conduct the research study 
according to the Protocol and applicable regulations and has signed the Investigator 
Agreement or the Clinical Study Agreement. 
 
The Investigator and his/her staff have sufficient time and facilities to conduct the study and 
that they have access to an adequate number of appropriate participants to conduct the study.  
 
Source documentation (including original medical records, if applicable) must be available to 
substantiate proper informed consent procedures, adherence to Protocol procedures, 
training records and appropriate delegation of roles, adequate reporting and follow-up of 
adverse events, accuracy of data collected on case report forms, and device information.  
 
If monitoring visits are scheduled, the Investigator/sponsor location will permit access to such 
records. A monitoring visit sign-in log will be maintained by study staff. The Investigator will 
agree to dedicate an adequate amount of time to the monitoring process. The Investigator 
and/or research coordinator will be available for monitoring visits. It is expected that the 
Investigator will provide the study monitor with a suitable working environment for review of 
study-related documents. 
8.5 
Deviations from Protocol 
The Investigator will ensure that the study does not deviate from the IRB approved Protocol for any 
reason without prior written approval from Sponsor except in cases of medical emergencies, when 
the deviation is necessary to protect the rights, safety and well-being of the participant or eliminate 
an apparent immediate hazard to the participant. In that event, the Investigator will notify Sponsor 
immediately by phone or in writing. All deviations must be reported to the Sponsor. In participant-
specific deviations from the Protocol, a Protocol deviation case report form will be completed. The 
occurrence of Protocol deviations will be monitored by the Sponsor for evaluation of investigator 
compliance to the Protocol and regulatory requirements and dealt with according to written 
procedures. Investigators will inform their IRB or equivalent committee of all Protocol deviations in 
accordance with their specific IRB or equivalent committee reporting policies and procedures.  
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 30 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
In the event of repeated non-compliance, as determined by the Sponsor, a Sponsor’s monitor or 
company representative will attempt to secure compliance by one or more of the following (and not 
limited to):  
 
Visiting the investigator and/or delegate 
 
Telephoning the investigator and/or delegate 
 
Corresponding with the investigator and/or delegate 
Repeated non-compliance with the signed agreement, the Protocol or any other conditions of the 
study may result in further escalation in accordance with the Sponsor’s written procedures including 
securing compliance or, at its sole discretion; Sponsor may terminate the investigator's participation 
in the study.  
8.6 
Quality Assurance Audit 
A Sponsor representative or designee may request access to all clinical study records, including 
source documentation, for inspection and duplication during a Quality Assurance audit.  
In the event that an investigator is contacted by a Regulatory Agency in relation to this clinical study, 
the Investigator will notify Sponsor immediately. The Investigator and Research Coordinator must 
be available to respond to reasonable requests and audit queries made during the audit process. 
The Investigator must provide Sponsor with copies of all correspondence that may affect the review 
of the current clinical study (e.g., Form FDA 483, Inspectional Observations, Warning Letters, 
Inspection Reports, etc.). Sponsor may provide any needed assistance in responding to regulatory 
audits. 
9.0 
DATA HANDLING AND RECORD KEEPING 
All CRF data collection will be performed by authorized personnel to enter, review or correct data in 
a secure EDC System. Access will be strictly confidential. 
For the clinical study duration, the Investigator will maintain complete and accurate documentation 
including, but not limited to, source documents, clinical study progress records, electronic case 
report forms, signed ICFs, device accountability records, correspondence with the IRB and clinical 
study monitor/Sponsor, adverse event reports, and information regarding participant discontinuation 
or completion of the clinical study.  Protocol deviations are not anticipated, but if they occur, they will 
be recorded in the EDC System.  All study related documents will be stored in a secured location. 
The handling, storage, transfer and destruction of the data will comply with all applicable national 
and local laws. 
The following persons will have access to identifiable data in order to review and ensure the Study 
is run appropriately: the Sponsor representatives (such as contract monitors or study managers) 
visiting the study sponsor location, the study staff participating and running the Study, regulatory (i.e. 
FDA) and health authorities.  Participants consenting to participate will allow these persons to read 
the identifiable information. 
The Sponsor (including persons working under the Sponsor) will have access to de-identified data 
only.  The Sponsor will take reasonable measures to keep the data confidential and secure. 
Data Management will include documentation of the systems and procedures used in data collection 
for the duration of the study. 
All CRF data collection will be performed by personnel authorized to enter, review or correct data. 
Data will be strictly confidential. 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 31 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
All CRF data will be reformatted into a data structure acceptable to iRhythm. The data will be 
subjected to consistency and validation checks and will be subject to supplemental validation. 
t the conclusion of the study, completed CRF images with the date-and-time stamped audit trail 
indicating the user, the data entered, and any reason for change (if applicable) will be archived for 
each sponsor location and a backup copy archived with iRhythm. 
9.1 
Source Documentation 
Regulations and Good Clinical Practice (GCP) require that the Investigator maintain information in 
the participant’s original source documents (including medical records) that corroborates data 
collected on the case report forms. In order to comply with these regulatory requirements/GCP, the 
following information should be included in the participant record as/if applicable to the study: 
 
Medical history/physical condition of the participant before involvement in the study sufficient 
to verify Protocol entry criteria 
 
Dated and signed notes on the day of entry into the study referencing the Sponsor, Protocol 
number, participant ID number and a statement that informed consent was obtained 
 
Dated and signed notes from each participant visit (for specific results of procedures and 
exams) 
 
Adverse events reported and their resolution including supporting documents such as 
discharge summaries, catheterization laboratory reports, ECGs, and lab results, etc. 
including documentation of awareness of SAEs and of investigator device relationship 
assessment of SAEs at the sponsor location 
 
Notes regarding prescription medications taken during the study. For those medications 
taken for the treatment of an Adverse Event the documentation should also include start and 
stop dates. 
 
Participant’s condition upon completion of or withdrawal from the study 
 
Any other documents or records required to substantiate data entered into the CRF 
9.2 
Case Report Form Completion 
Primary data collection based on source-document review will be performed clearly and accurately 
by study personnel trained on the Protocol and CRF completion. CRF data will be collected for all 
participants in the study.  In the event the EDC System is unavailable, study personnel may complete 
paper CRFs and enter the data in the EDC System as soon as it is available.    
9.3 
Direct Access to Source Data/Documents 
The investigator/institution will permit direct access to source data/documents in order for clinical 
study-related monitoring, audits, IRB review and regulatory inspections to be performed. 
Participants providing informed consent are agreeing to allow Sponsor and/or its designee access 
and copying rights to pertinent information in their source document concerning their participation in 
this clinical study. The investigator will obtain, as part of the informed consent, permission for clinical 
study monitors or regulatory authorities to review, in confidence, any records identifying the 
participants in this clinical study. This information may be shared with regulatory agencies; however, 
Sponsor undertakes not to otherwise release the participant's personal and private information. 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 32 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
9.4 
Record Retention 
The Sponsor will archive and retain all documents pertaining to the study as per the applicable 
regulatory record retention requirements. The Investigator must obtain permission from Sponsor in 
writing before destroying or transferring control of any clinical study records. 
10.0 
ETHICAL CONSIDERATION 
10.1 
Institutional Review Board Review 
Institutional Review Board approval for the Protocol, ICF and other written information provided to 
the patient will be obtained by the Principal Investigator at each sponsor location or community 
clinical study site prior to participation in this validation study. The approval letter must be received 
prior to the start of this validation study and a copy must be provided to the Sponsor. No changes 
will be made to the Protocol or ICF or other written information provided to the patient/participant 
without appropriate approvals, including IRB, the Sponsor, and/or the regulatory agencies.  
Until the validation study is completed, the Investigator will advise the IRB of the progress of this 
study, per IRB requirements. Ongoing written approval will be obtained according to the IRB 
requirements. Additionally, any amendments to the Protocol as well as associated ICF changes will 
be submitted to the IRB and written approval obtained prior to implementation. 
11.0 
PUBLICATION POLICY 
The data and results from the study are the sole property of the Sponsor. The Sponsor shall have 
the right to access and use all data and results generated during this wear validation study. The 
Sponsor may publish a manuscript regarding the study results.  The recorded ECG information may 
be used for educational (including medical publications) or training purposes only, but only de-
identified information will be used. 
The preliminary and final reports from the patch for those participants who were enrolled through the 
community clinic study site belong to the participant as part of their medical record. 
12.0 
RISK ANALYSIS 
12.1 
Anticipated Clinical Benefits 
This is a post-clearance study on the extended wear performance of the study device. Study 
participants will be asked to wear the device for as long as possible (up to 30 days) to validate 
performance of the device in up to 21 days of wear.  There are no immediate potential benefits to 
study participants; the primary long-range potential benefit is improvement in clinical standard of 
care for others (altruistic benefit to study participants).  
12.2 
Foreseeable Adverse Events and Anticipated Adverse Device Effects 
Table 3 provides a list of anticipated adverse events with wearing the study device.  If a participant 
experiences severe reaction to the device, it is recommended that the participant remove the device.  
 
 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 33 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
Table 3: Foreseeable / Anticipated Adverse Device Effects 
Anticipated Adverse 
Device Effects (ADE)
ADE Definition 
Allergic reaction 
Localized allergic reaction or allergic symptoms (i.e., acute urticaria) 
associated with serious injury.
Delayed healing 
Atypical or otherwise prolonged recovery period post-wear resulting in non-
permanent injury.
Discomfort 
Transient physical or psychological distress. 
Infection (local) 
Localized evidence of tissue invasion by pathogenic microorganisms, 
resulting in non-permanent tissue injury.
Infection (systemic) 
Evidence of pathogenic microorganism proliferation progressed to a 
systemic disease state associated with serious injury.
Non-functional defects 
Defects that are imperceptible to participant but identified by study staff 
(i.e., compromised aesthetics).
Pain 
Transient physical or psychological suffering or other unpleasant feelings. 
Skin or soft tissue 
damage (permanent, 
major)
Serious injury presenting as permanent signs of tissue structural or 
functional damage (i.e., gross scarring, localized neuropathy). 
Skin or soft tissue 
damage (permanent, 
minor)
Serious injury presenting as permanent changes in epidermis (i.e., 
abnormal pigmentation, blemishes). 
Skin or soft tissue 
damage (temporary, 
major)
Signs of probable irritant contact dermatitis (edema, erythema, pruritus). 
Skin or soft tissue 
damage (temporary, 
minor)
Minor irritation, not yet at probable irritant contact dermatitis. 
Participant annoyance 
Inconvenience perceptible to participant but unlikely to cause injury. 
Participant 
inconvenience
Inconvenience imperceptible to participant but identified by study staff (i.e., 
burdensome packaging).
 
12.3 
Risks Associated with Participation in Clinical Study 
Participation in the study requires submission of data that may or may not be protected heath 
information.  This information will be kept confidential, but there is a risk that some of the information 
could be unintentionally made non-confidential.  The risk of this happening for this study is no greater 
than the risk of loss of confidentiality in any study.   
12.4 
Possible Interactions with Protocol-Required Concomitant Medications 
There are no protocol-required medications being used as part of this study. Due to the nature of 
some medications having effect on the skin, a list of current medications will be requested at the 
Baseline visit. New medications that are added during the course of the patch wear will also be 
requested.   
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 34 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
12.5 
Steps That Will be Taken to Control or Mitigate Risks 
Risks associated with the use of the device during this clinical study are minimized through device 
design, investigator selection and training, pre-specified patient eligibility requirements, and study 
monitoring to ensure adherence to the protocol.   
Devices manufactured for this extended wear study will be the design cleared in K202359, with minor 
improvements in manufacturability and with the modifications necessary to allow for ECG recording 
up to 30 days.  The Sponsor will have completed and documented internal Design Control 
requirements for all components of the study devices prior to first use in the extended wear study.  
All adverse events and device deficiencies will be reported to iRhythm and will be monitored 
internally for safety surveillance purposes. 
The contraindications, warnings and precautions are listed in the IFU in the Zio monitor Clinical 
Reference Manual (Part Number DLB0035 or clinical study equivalent) that will be provided with all 
devices to be used during this study.  
12.6 
Risk to Benefit Rationale 
Foreseeable risks are outlined in Table 3.  There are no other types of foreseeable risk to participants 
by virtue of participation in this study.  Apparently healthy study participants will equally be exposed 
to such physical risks, but will be fully informed in order to assess the wear performance of the 
investigational device on a human skin.  The value of the information to be gained outweighs these 
procedural-related risks as it will support intended performance of the device. 
Participants participating in this study will be receiving the latest technology of the currently cleared 
Zio monitor patch.  
Participants participating in the study have a small risk of loss of confidentiality as part of the data 
collection process.  This risk is mitigated to as low as possible with the use of data collection systems, 
methods and procedures that are used commonly in clinical research.  This includes the use of only 
validated electronic systems, the training of study personnel and the use of pseudo anonymized data 
for all data entry.  Based upon the established safety profile of the study device, the low risk of loss 
of confidentiality is adequately mitigated to justify use of the study device for participants in this study. 
 
 
 
 
 
This area intentionally left blank 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 35 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
 
APPENDIX I:  ABBREVIATIONS AND ACRONYMS 
 
 
 
 
 
 
 
 
AE 
Adverse Event 
CRF 
Case Report Form 
DD 
Device Deficiency 
DM 
Device Malfunction 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
FDA 
U.S. Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
SAE 
Serious Adverse Event 
UADE 
Unanticipated Adverse Device Event 
USADE 
Unanticipated Serious Adverse Device Event 
 
 
 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 36 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
APPENDIX II:  DEFINITIONS 
 
DEATH (All Cause) 
All deaths regardless of cause.  Death is further divided into 2 categories: 
1.  CARDIOVASCULAR DEATH  
Per the Valve Academic Research Consortium (VARC) [11], as any one of the following: 
 
Any death due to proximate cardiac cause (e.g. MI, cardiac tamponade, worsening 
heart failure) 
 
Unwitnessed death and death of unknown cause 
 
All procedure-related deaths, including those related to a complication of the 
procedure or treatment for a complication of the procedure 
 
Death caused by non-coronary vascular conditions such as cerebrovascular 
disease, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or 
other vascular disease 
2. NON-CARDIOVASCULAR DEATH 
Any death not covered by the VARC definitions of Cardiovascular Death, such as death 
caused by infection, malignancy, sepsis, pulmonary causes, accident, suicide, or trauma. 
FITZPATRICK SKIN TYPE 
The Fitzpatrick skin type is a 6-point scale [12]. 
 
Fitzpatrick 
Skin Type 
Skin 
Skin Reaction to Sun Exposure 
I 
Pale White 
Always Burns, Never Tans 
II 
Fair 
Usually Burns, Tans Minimally 
III 
Darker White 
Sometimes Mild Burn, Tans Uniformly 
IV 
Light Brown 
Burn Minimally, Always Tans Well 
V 
Brown 
Very Rarely burns, Tans Very Easily 
VI 
Dark Brown or Black 
Never Burns 
HOSPITALIZATION (ALL CAUSE) 
Defined as admission to inpatient unit or ward in the hospital for at least 24 hours, including 
emergency department stay.  Excludes hospitalizations planned for pre-existing conditions, unless 
there is worsening of a pre-existing condition.  
HYPERHYDROSIS STATE 
Hyperhidrosis status will be determined by the following definition: 
• 
Primary – Focal, visible, and excessive sweating for no apparent cause. Typically at axillae, 
palms, soles, inguinal areas, and face. 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 37 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
• 
Secondary – Caused by underlying medical condition.  Can be either focal or general 
sweating. 
• 
None – Only sweat during exercise, hot environment, physical, and/or psychological stress 
CHEST HAIR DENSITY 
Chest hair density will be measured by visual inspection and classified as smooth/no hair, some hair, 
moderately hairy, or very hairy in the target patch placement area. 
SKIN IRRITATION 
Severity of skin irritation will be assessed per Table 4 below.  Interpretation of the reaction will be 
based on the method recommended by the International Contact Dermatitis Research Group 
(ICDRG) [10,13]. This scale has been modified to incorporate the U.S. Food & Drug Administration 
(FDA) Guidance for Industry Skin Irritation and Sensitization Testing of Generic Transdermal Drug 
Products. 
Table 4: Skin Irritation Assessment 
 
Negative reaction 
(= -) 
 
 
 
Weak positive reaction 
Erythema Infiltration Discrete 
papules ( = +) 
FDA = 1 minimal erythema, 
barely perceptible 
 
Doubtful reaction 
Faint macular or homogeneous 
erythema, no infiltration (= ?) 
FDA = 0 no evidence of irritation 
 
Strong positive reaction 
Erythema Infiltration Papules 
Discrete vesicles ( = ++) 
FDA = 2-3 definite erythema, 
readily visible, papules 
 
Irritant reaction of different 
types* (= IR) 
 
Extreme positive reaction 
Coalescing vesicles/bullous 
reaction (= +++) 
FDA = 4-7 definite edema, 
erythema, papules, vesicular 
eruption, spreading beyond site 
SKIN TYPE 
Skin type will be assessed at the planned patching location of the study device. 
• 
Normal 
• 
Dry – Scaling (visible peeling of outer skin layer) and skin cracking; also known as xeroderma 
• 
Oily – Excess sebum (oil) production producing shiny appearance; also known as seborrhea 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 38 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
 
VULNERABLE POPULATION (ICH E6(R2) Definition) 
Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the 
expectation, whether justified or not, of benefits associated with participation, or of a retaliatory 
response from senior members of a hierarchy in case of refusal to participate. Examples are 
members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing 
students, subordinate hospital and laboratory personnel, employees of the pharmaceutical industry, 
members of the armed forces, and persons kept in detention. Other vulnerable participants include 
those with incurable diseases, persons in nursing homes, unemployed or impoverished persons, 
persons in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, 
minors, and those incapable of giving consent.   
 
 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 39 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
BIBLIOGRAPHY 
1. Turakhia MP, Hoang DD, Zimetbaum P, Miller JD, Froelicher VF, Kumar UN, Xu X, Yang F, 
Heidenreich PA. Diagnostic utility of a novel leadless arrhythmia monitoring device. Am J 
Cardiol. 2013;112:520–524. 
2. Survey data on file. 
3. Knight BP, et al.  Performance of a Novel Next-Generation Ambulatory ECG Long-Term 
Patch Monitor: A Multicenter Post- Market Evaluation.  Heart Rhythm 2024;21(9 Suppl):S796. 
4. Barrett PM, Komatireddy R, Haaser S, Topol S, Sheard J, Encinas J, Fought AJ, Topol EJ. 
Comparison of 24-hour Holter Monitoring with 14-day Novel Adhesive Patch 
Electrocardiographic Monitoring. The American Journal of Medicine. 2014;127:95.e11-
95.e17. 
5. Rosenberg MA, Samuel M, Thosani A, Zimetbaum PJ. Use of a noninvasive continuous 
monitoring device in the management of atrial  fibrillation: a pilot study. Pacing Clin 
Electrophysiol. 2013;36:328–333. 
6. Kaura A, Sztriha L, Chan FK, Aeron-Thomas J, Gall N, Piechowski-Jozwiak B, Teo JT. Early 
prolonged ambulatory cardiac monitoring in stroke (EPACS): An open-label randomised 
controlled trial. Eur J Med Res. 2019;24:25. 
7. Gupta N, Yang J, Reynolds K, Lenane J, Garcia E, Sung SH, Harrison TN, Solomon MD, Go 
AS. Diagnostic Yield, Outcomes, and Resource Utilization With Different Ambulatory 
Electrocardiographic Monitoring Strategies. Am J Cardiol. 2022;166:38-44. 
8. Reynolds MR, Passman R, Swindle J, Mohammadi I, Wright B, Boyle K, Turakhia MP, Mittal 
S. Comparative effectiveness and healthcare utilization for ambulatory cardiac monitoring 
strategies in Medicare beneficiaries. Am Heart J. 2024;269:25-34. 
9. Hannun AY, Rajpurkar P, Haghpanahi M, Tison GH, Bourn C, Turakhia MP, Ng AY. 
Cardiologist-level arrhythmia detection and classification in ambulatory electrocardiograms 
using a deep neural network. Nat Med. 2019;25:65–69. 
10. Fonacier L, et. al.; American Academy of Allergy, Asthma & Immunology; American College 
of Allergy, Asthma & Immunology; Joint Council of Allergy, Asthma & Immunology. Contact 
dermatitis: a practice parameter-update 2015. J Allergy Clin Immunol Pract. 2015 May-
Jun;3(3 Suppl):S1-39. 
11. Updated standardized endpoint definitions for transcatheter aortic valve implantation: The 
Valve Academic Research Consortium-2 consensus document. Kappetein, A. Pieter et al.  
The Journal of Thoracic and Cardiovascular Surgery, Volume 145, Issue 1, 6 – 23 
12. Fitzpatrick TB. The validity and practicality of sun-reactive skin types I through VI. Arch 
Dermatol. 1988 Jun;124(6):869-71. 
13. Rietschel RL, Fowler JF Jr. Fisher's Contact Dermatitis. 5th ed. Baltimore, Md: Williams & 
Wilkins; 2001.   
 
 
 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

                                          PN# TP rev. 01 
2024-11-14_SHASTA II_Clean FINAL V1 PROT 
Page 40 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
REVISION HISTORY 
Version # 
Released Date 
Description of Change 
01 
15 November 2024 
Initial Release 
 
 
 
Docusign Envelope ID: D5497427-2AB8-4C9B-9DCC-E8C38FF42891

Certificate Of Completion
Envelope Id: D54974272AB84C9B9DCCE8C38FF42891
Status: Completed
Subject: Complete with Docusign: 2024-11-14_SHASTA II_Clean FINAL V1 PROT.pdf
Source Envelope: 
Document Pages: 40
Signatures: 8
Envelope Originator: 
Certificate Pages: 6
Initials: 0
Char Bame
AutoNav: Enabled
EnvelopeId Stamping: Enabled
Time Zone: (UTC-08:00) Pacific Time (US & Canada)
650 Townsend St Ste 380
San Francisco, CA  94103-6248
char.bame@irhythmtech.com
IP Address: 73.232.122.244 
Record Tracking
Status: Original
             11/15/2024 12:17:16 PM
Holder: Char Bame
             char.bame@irhythmtech.com
Location: DocuSign
Signer Events
Signature
Timestamp
Chanda Owens
chanda.owens@irhythmtech.com
Security Level: Email, Account Authentication 
(None)
Signature Adoption: Pre-selected Style
Using IP Address: 68.5.133.129
Sent: 11/15/2024 12:23:56 PM
Viewed: 11/15/2024 2:15:56 PM 
Signed: 11/15/2024 2:16:06 PM
Electronic Record and Signature Disclosure: 
      Accepted: 11/15/2024 2:15:56 PM
      ID: 786934dc-5bbd-43f3-bc88-efbbfdb87c0f
Charlotte M Bame
char.bame@irhythmtech.com
Director, Clin. Research Ops
iRhythm Technologies, Inc.
Security Level: Email, Account Authentication 
(None)
Signature Adoption: Pre-selected Style
Using IP Address: 73.232.122.244
Sent: 11/15/2024 12:23:57 PM
Viewed: 11/15/2024 12:37:16 PM 
Signed: 11/15/2024 12:55:42 PM
Electronic Record and Signature Disclosure: 
      Not Offered via DocuSign
Chevy Brown
chevy.brown@irhythmtech.com
Security Level: Email, Account Authentication 
(None)
Signature Adoption: Pre-selected Style
Using IP Address: 99.147.221.54
Signed using mobile
Sent: 11/15/2024 12:23:58 PM
Viewed: 11/15/2024 12:30:48 PM 
Signed: 11/15/2024 12:31:09 PM
Electronic Record and Signature Disclosure: 
      Not Offered via DocuSign
Christine Dunn
christine.dunn@irhythmtech.com
Sr. RA Mgr. International
Security Level: Email, Account Authentication 
(None)
Signature Adoption: Uploaded Signature Image
Using IP Address: 67.160.87.74
Sent: 11/15/2024 12:24:01 PM
Viewed: 11/15/2024 1:12:41 PM 
Signed: 11/15/2024 1:12:50 PM
Electronic Record and Signature Disclosure: 
      Accepted: 11/15/2024 1:12:41 PM
      ID: 46ce8249-d0aa-4a1e-ae74-d340d400435a

Signer Events
Signature
Timestamp
Kevin Clarkson
kevin.clarkson@irhythmtech.com
Director, Zio XT
Security Level: Email, Account Authentication 
(None)
Signature Adoption: Pre-selected Style
Using IP Address: 71.255.89.116
Sent: 11/15/2024 12:23:58 PM
Viewed: 11/15/2024 1:51:24 PM 
Signed: 11/15/2024 1:51:30 PM
Electronic Record and Signature Disclosure: 
      Accepted: 11/15/2024 1:51:24 PM
      ID: 969daf84-c862-40fc-a06d-c777f5494b2a
Minang Turakhia
mintu.turakhia@irhythmtech.com
CMO
Security Level: Email, Account Authentication 
(None)
Signature Adoption: Pre-selected Style
Using IP Address: 205.220.129.25
Signed using mobile
Sent: 11/15/2024 12:23:59 PM
Viewed: 11/15/2024 12:35:24 PM 
Signed: 11/15/2024 12:48:25 PM
Electronic Record and Signature Disclosure: 
      Accepted: 11/15/2024 12:35:24 PM
      ID: 7ad8e83f-c5ce-4c04-8ef5-a58244cfdf39
TJ Battisti
tj.battisti@irhythmtech.com
Security Level: Email, Account Authentication 
(None)
Signature Adoption: Pre-selected Style
Using IP Address: 99.196.129.117
Signed using mobile
Sent: 11/15/2024 12:24:00 PM
Viewed: 11/15/2024 1:06:22 PM 
Signed: 11/15/2024 1:11:34 PM
Electronic Record and Signature Disclosure: 
      Accepted: 11/15/2024 1:06:22 PM
      ID: a80456f6-2088-4415-8e92-d2a641081bc3
Vladimir Fokin
vladimir.fokin@irhythmtech.com
Director, Data Management and Biostatistics
Security Level: Email, Account Authentication 
(None)
Signature Adoption: Pre-selected Style
Using IP Address: 47.227.204.35
Sent: 11/15/2024 12:24:00 PM
Viewed: 11/15/2024 12:27:07 PM 
Signed: 11/15/2024 12:32:06 PM
Electronic Record and Signature Disclosure: 
      Accepted: 11/15/2024 12:27:07 PM
      ID: c650b1ee-f564-46d0-9932-31d110c5d9fc
In Person Signer Events
Signature
Timestamp
Editor Delivery Events
Status
Timestamp
Agent Delivery Events
Status
Timestamp
Intermediary Delivery Events
Status
Timestamp
Certified Delivery Events
Status
Timestamp
Carbon Copy Events
Status
Timestamp
Witness Events
Signature
Timestamp
Notary Events
Signature
Timestamp

Envelope Summary Events
Status
Timestamps
Envelope Sent
Hashed/Encrypted
11/15/2024 12:24:01 PM
Certified Delivered
Security Checked
11/15/2024 12:27:07 PM
Signing Complete
Security Checked
11/15/2024 12:32:06 PM
Completed
Security Checked
11/15/2024 2:16:06 PM
Payment Events
Status
Timestamps
Electronic Record and Signature Disclosure

ELECTRONIC RECORD AND SIGNATURE DISCLOSURE  
From time to time, iRhythm Technologies, Inc. (we, us or Company) may be required by law to 
provide to you certain written notices or disclosures. Described below are the terms and 
conditions for providing to you such notices and disclosures electronically through the DocuSign 
system. Please read the information below carefully and thoroughly, and if you can access this 
information electronically to your satisfaction and agree to this Electronic Record and Signature 
Disclosure (ERSD), please confirm your agreement by selecting the check-box next to ‘I agree to 
use electronic records and signatures’ before clicking ‘CONTINUE’ within the DocuSign 
system. 
 
Getting paper copies  
At any time, you may request from us a paper copy of any record provided or made available 
electronically to you by us. You will have the ability to download and print documents we send 
to you through the DocuSign system during and immediately after the signing session and, if you 
elect to create a DocuSign account, you may access the documents for a limited period of time 
(usually 30 days) after such documents are first sent to you. After such time, if you wish for us to 
send you paper copies of any such documents from our office to you, you will be charged a 
$0.00 per-page fee. You may request delivery of such paper copies from us by following the 
procedure described below. 
 
Withdrawing your consent  
If you decide to receive notices and disclosures from us electronically, you may at any time 
change your mind and tell us that thereafter you want to receive required notices and disclosures 
only in paper format. How you must inform us of your decision to receive future notices and 
disclosure in paper format and withdraw your consent to receive notices and disclosures 
electronically is described below. 
 
Consequences of changing your mind  
If you elect to receive required notices and disclosures only in paper format, it will slow the 
speed at which we can complete certain steps in transactions with you and delivering services to 
you because we will need first to send the required notices or disclosures to you in paper format, 
and then wait until we receive back from you your acknowledgment of your receipt of such 
paper notices or disclosures. Further, you will no longer be able to use the DocuSign system to 
receive required notices and consents electronically from us or to sign electronically documents 
from us. 
 
All notices and disclosures will be sent to you electronically  
Electronic Record and Signature Disclosure created on: 1/5/2021 2:43:58 PM
Parties agreed to: Chanda Owens, Christine Dunn, Kevin Clarkson, Minang Turakhia, TJ Battisti, Vladimir Fokin

Unless you tell us otherwise in accordance with the procedures described herein, we will provide 
electronically to you through the DocuSign system all required notices, disclosures, 
authorizations, acknowledgements, and other documents that are required to be provided or made 
available to you during the course of our relationship with you. To reduce the chance of you 
inadvertently not receiving any notice or disclosure, we prefer to provide all of the required 
notices and disclosures to you by the same method and to the same address that you have given 
us. Thus, you can receive all the disclosures and notices electronically or in paper format through 
the paper mail delivery system. If you do not agree with this process, please let us know as 
described below. Please also see the paragraph immediately above that describes the 
consequences of your electing not to receive delivery of the notices and disclosures 
electronically from us. 
 
How to contact iRhythm Technologies, Inc.:  
You may contact us to let us know of your changes as to how we may contact you electronically, 
to request paper copies of certain information from us, and to withdraw your prior consent to 
receive notices and disclosures electronically as follows: 
To contact us by email send messages to: _hr@irhythmtech.com 
 
To advise iRhythm Technologies, Inc. of your new email address  
To let us know of a change in your email address where we should send notices and disclosures 
electronically to you, you must send an email message to us at _hr@irhythmtech.com and in the 
body of such request you must state: your previous email address, your new email address.  We 
do not require any other information from you to change your email address.  
If you created a DocuSign account, you may update it with your new email address through your 
account preferences.  
 
To request paper copies from iRhythm Technologies, Inc.  
To request delivery from us of paper copies of the notices and disclosures previously provided 
by us to you electronically, you must send us an email to _hr@irhythmtech.com and in the body 
of such request you must state your email address, full name, mailing address, and telephone 
number. We will bill you for any fees at that time, if any. 
 
To withdraw your consent with iRhythm Technologies, Inc.  
To inform us that you no longer wish to receive future notices and disclosures in electronic 
format you may: 

i. decline to sign a document from within your signing session, and on the subsequent page, 
select the check-box indicating you wish to withdraw your consent, or you may; 
ii. send us an email to _hr@irhythmtech.com and in the body of such request you must state your 
email, full name, mailing address, and telephone number. We do not need any other information 
from you to withdraw consent..  The consequences of your withdrawing consent for online 
documents will be that transactions may take a longer time to process.. 
 
Required hardware and software  
The minimum system requirements for using the DocuSign system may change over time. The 
current system requirements are found here: https://support.docusign.com/guides/signer-guide-
signing-system-requirements.  
 
Acknowledging your access and consent to receive and sign documents electronically  
To confirm to us that you can access this information electronically, which will be similar to 
other electronic notices and disclosures that we will provide to you, please confirm that you have 
read this ERSD, and (i) that you are able to print on paper or electronically save this ERSD for 
your future reference and access; or (ii) that you are able to email this ERSD to an email address 
where you will be able to print on paper or save it for your future reference and access. Further, 
if you consent to receiving notices and disclosures exclusively in electronic format as described 
herein, then select the check-box next to ‘I agree to use electronic records and signatures’ before 
clicking ‘CONTINUE’ within the DocuSign system. 
By selecting the check-box next to ‘I agree to use electronic records and signatures’, you confirm 
that: 
 
You can access and read this Electronic Record and Signature Disclosure; and 
 
You can print on paper this Electronic Record and Signature Disclosure, or save or send 
this Electronic Record and Disclosure to a location where you can print it, for future 
reference and access; and 
 
Until or unless you notify iRhythm Technologies, Inc. as described above, you consent to 
receive exclusively through electronic means all notices, disclosures, authorizations, 
acknowledgements, and other documents that are required to be provided or made 
available to you by iRhythm Technologies, Inc. during the course of your relationship 
with iRhythm Technologies, Inc.. 

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 1 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
 
 
 
 
 
 
 
 
 
Validation Study: Extended Wear Performance of the Zio monitor – SHASTA II 
Protocol Number 
IRT-003-2024 
Version Number 
2.0 
Date 
April 15, 2025 
Principal Investigator 
Minang Turakhia, MD 
Planned Number of Locations and Region(s) 
Up to Five Study Centers in the US 
Protocol Author  
TJ Battisti, Ph.D. 
 
 
 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 2 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
 
 
 
Task 
Name 
Function 
Signature 
Date 
Written by 
TJ Battisti 
Director, Scientific 
Affairs 
 
 
Reviewed 
by 
Chevy Brown 
Sr. Manager, 
Clinical Research 
 
 
Reviewed 
by 
Christine Dunn 
Director, Regulatory 
Affairs 
 
 
Approved 
by 
Charlotte Bame 
Sr. Director, Global 
Clinical Research 
Operations 
 
 
Approved 
by 
Chanda Owens 
VP, Quality 
Assurance 
 
 
Approved 
by 
Minang Turakhia 
Chief Medical & 
Scientific Officer & 
EVP, Product 
Innovation 
 
 
Approved 
by 
Vladimir Fokin 
Director, Data 
Management and 
Biostatistics 
 
 
Approved 
by 
Kevin Clarkson 
Sr. Director, 
Product 
Management 
 
 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3
04/29/2025
04/23/2025
04/23/2025
04/24/2025
04/24/2025
04/30/2025
04/23/2025
04/23/2025

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 3 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
 
Table of Contents 
TABLE OF CONTENTS ......................................................................................................................... 3 
COMPLIANCE STATEMENT .................................................................................................................. 6 
INVESTIGATOR SIGNATURE PAGE ....................................................................................................... 7 
PROTOCOL SUMMARY ........................................................................................................................ 8 
1.0 
INTRODUCTION .................................................................................................................... 11 
1.1 
Study Design .................................................................................................................... 11 
1.2 
Study Objectives .............................................................................................................. 11 
2.0 
BACKGROUND AND RATIONALE ............................................................................................ 11 
2.1 
Name of the Device .......................................................................................................... 12 
2.2 
Intended Indication for Use ............................................................................................... 12 
2.3 
Description of the Device .................................................................................................. 12 
2.4 
Number of Participants ..................................................................................................... 14 
2.5 
Overall Flow of the Study and Follow-up Schedule .............................................................. 14 
2.5.1 Study Safety Committee................................................................................................ 16 
3.0 
STUDY PERFORMANCE OBJECTIVES AND ADDITIONAL MEASURES .......................................... 16 
3.1 
Wear Time Performance Objective ..................................................................................... 16 
3.2 
Analyzable Time Performance Objective ............................................................................ 16 
3.3 
Safety Measures .............................................................................................................. 16 
3.4 
Additional Device Measures .............................................................................................. 17 
3.5 
Other Measures ............................................................................................................... 17 
4.0 
PARTICIPANT SELECTION AND WITHDRAWAL ......................................................................... 17 
4.1 
Participant Recruitment Population and Retention ............................................................. 17 
4.2 
Participant Screening and Informed Consent ..................................................................... 17 
4.2.1 Participant Screening ................................................................................................... 18 
4.2.2 Informed Consent ......................................................................................................... 18 
4.2.3 Disclosure of Participant Personal Contact Information ................................................... 18 
4.3 
Eligibility Criteria .............................................................................................................. 18 
4.3.1 Inclusion Criteria .......................................................................................................... 19 
4.3.2 Exclusion Criteria .......................................................................................................... 19 
4.4 
Participant Enrollment and Inclusion ................................................................................. 19 
4.5 
Participant Payment ......................................................................................................... 19 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 4 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
4.6 
Participant Discontinuation ............................................................................................... 20 
4.6.1 Lost-to-Follow-up: ......................................................................................................... 20 
4.7 
Number of Participants Required to be Included in the Study .............................................. 20 
4.8 
Estimated Time Needed to Enroll this Number ................................................................... 20 
4.9 
Expected Duration of Each Participant’s Role ..................................................................... 20 
4.10 
Total Expected Duration of the Study ................................................................................. 20 
4.11 
Study Participant Completion ............................................................................................ 20 
5.0 
BASELINE VISIT AND FOLLOW-UP ASSESSMENTS .................................................................. 21 
5.1 
Baseline (Visit 1) .............................................................................................................. 21 
5.2 
Patch Wear Period ............................................................................................................ 22 
5.3 
Protocol Required Medications ......................................................................................... 22 
5.4 
7-Day and 14-Day (+ 3 days) Participant (Phone Call or Video Visit 2 & 3) ............................ 22 
5.5 
21-Day (+3 days) Participant Follow-up (Visit 4).................................................................. 23 
5.6 
30-Day (±3 days) Participant Follow-up (Visit 5).................................................................. 23 
6.0 
ADVERSE EVENTS ................................................................................................................ 24 
6.1 
Definitions ....................................................................................................................... 25 
6.1.1 Adverse Event .............................................................................................................. 25 
6.1.2 Serious Adverse Event .................................................................................................. 25 
6.1.3 Device Malfunction ....................................................................................................... 25 
6.2 
Device, Process or Procedure Relationship ........................................................................ 26 
6.2.1 Unanticipated (Serious Adverse) Device Effect [U(S)ADE] ................................................ 26 
6.3 
Adverse Event/Device Deficiency/Product Experience Reporting ......................................... 26 
6.3.1 Adverse Event Reporting ............................................................................................... 26 
6.3.2 Unanticipated Serious Adverse Device Effect Reporting .................................................. 26 
6.3.3 Device Deficiency/Device Malfunction Reporting ............................................................ 26 
6.3.4 Adverse Event Reporting to Country Regulatory Authorities by the Sponsor ...................... 27 
7.0 
STATISTICAL ANALYSIS ......................................................................................................... 27 
7.1 
Analysis Population .......................................................................................................... 27 
7.2 
Sample Size Calculations and Assumptions ....................................................................... 27 
7.3 
Planned Interim Analyses ................................................................................................. 27 
7.4 
Statistical Analyses .......................................................................................................... 27 
7.4.1 Subgroup Analysis ........................................................................................................ 28 
8.0 
QUALITY CONTROL AND QUALITY ASSURANCE ....................................................................... 28 
8.1 
Selection of Study Site Locations and Investigators ............................................................ 28 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 5 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
8.2 
Protocol Amendments ...................................................................................................... 28 
8.3 
Training ........................................................................................................................... 28 
8.3.1 Study Training .............................................................................................................. 28 
8.3.2 Training of Sponsor’s Monitors ...................................................................................... 29 
8.4 
Monitoring ....................................................................................................................... 29 
8.5 
Deviations from Protocol ................................................................................................... 29 
8.6 
Quality Assurance Audit .................................................................................................... 30 
9.0 
DATA HANDLING AND RECORD KEEPING ............................................................................... 30 
9.1 
Source Documentation ..................................................................................................... 30 
9.2 
Case Report Form Completion .......................................................................................... 31 
9.3 
Direct Access to Source Data/Documents ......................................................................... 31 
9.4 
Record Retention ............................................................................................................. 31 
10.0 
ETHICAL CONSIDERATION ..................................................................................................... 31 
10.1 
Institutional Review Board Review ..................................................................................... 31 
11.0 
PUBLICATION POLICY ........................................................................................................... 32 
12.0 
RISK ANALYSIS .................................................................................................................... 32 
12.1 
Anticipated Clinical Benefits .............................................................................................. 32 
12.2 
Foreseeable Adverse Events and Anticipated Adverse Device Effects .................................. 32 
12.3 
Risks Associated with Participation in Clinical Study ........................................................... 33 
12.4 
Possible Interactions with Protocol-Required Concomitant Medications ............................... 33 
12.5 
Steps That Will be Taken to Control or Mitigate Risks ......................................................... 33 
12.6 
Risk to Benefit Rationale .................................................................................................. 33 
APPENDIX I:  ABBREVIATIONS AND ACRONYMS ................................................................................. 35 
APPENDIX II:  DEFINITIONS ............................................................................................................... 36 
REVISION HISTORY .......................................................................................................................... 40 
 
 
 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 6 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
 
COMPLIANCE STATEMENT  
 
This Study will be conducted in accordance with this Protocol, the Declaration of Helsinki, applicable Good 
Clinical Practices and applicable regulations and standards (e.g., US 21 CFR Parts 50, 56, 812, and 
820.30, US 45 CFR Part 46, ISO 14155:2020, and ISO 13485) and the appropriate local legislation(s).  
The most stringent requirements, guidelines or regulations must always be followed. The conduct of the 
study will be approved by the appropriate Institutional Review Board (IRB) of the respective sponsor 
locations and by the applicable regulatory authorities, when applicable. 
 
 
 
 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 7 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
INVESTIGATOR SIGNATURE PAGE 
I have read this Clinical Investigation Plan and agree to adhere to the requirements described in this plan, 
including but not restricted to the latest version of the Declaration of Helsinki, Good Clinical Practice, ISO 
14155, Code of Federal Regulations Title 21, and applicable local, regional and national regulatory 
requirements.  
I will ensure that no study-specific tests or procedures will be undertaken prior to Institutional Review 
Board (IRB) approval and/or any other local, regional and national approvals have been obtained. 
Reporting requirements and conditions imposed by the relevant IRB will be observed and followed.  
Any participant enrolled in the study will be fully informed about the study objectives and scope and 
signed informed consent will be obtained before any study specific procedures are initiated.  
I will also ensure that all site staff under my supervision will be trained adequately about the study scope 
and requirements, and I will supervise the study conduct in accordance with above stated regulations.  
First Name: 
 
Last Name: 
 
Title: 
 
Signature: 
 
Date: 
 
 
           MM/DD/YYYY 
 
One copy for the Principal Investigator, one copy for iRhythm Technologies, Inc. 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 8 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
PROTOCOL SUMMARY 
 
Protocol Number  
IRT-003-2024 
Title 
Validation Study: Extended Wear Performance of the Zio monitor¹ – 
SHASTA II  
Objective 
To evaluate the wear performance of the Zio monitor device in a 
representative population over an extended wear period (of up to 30 
continuous days) to demonstrate that the device can be worn with 
adequate patch adherence and signal quality through 21 days.  
Assessment of wear performance will include evaluation of the wear 
duration 
of 
the 
patch 
and 
percentage 
of 
analyzable 
electrocardiographic time.   
Product safety will be assessed by collection of all adverse events. 
Study Device 
Zio monitor 
Targeted Number of 
Participants  
A total of up to 150 participants will be enrolled at US iRhythm 
locations. The study may enroll participants from the community 
surrounding San Francisco, CA and Deerfield, IL as referred by 
FieldWork® (or another recruitment vendor) at the iRhythm clinic in 
those locations.  
Study Design 
A prospective, multi-center, single-arm study to validate the design of 
the Zio monitor/Zio MCT device form factor in extended (21-day) wear 
when utilizing an updated skin prep process. 
Performance 
Objectives and 
Measures  
Performance Objectives 
Mean wear duration and percent analyzable time of the Zio monitor 
will be assessed.  Performance goals include mean wear duration of 
21 days and percent analyzable time of 80%.   
Performance objectives will be met if the mean wear duration is 
greater than 21 days, and percent analyzable time is greater than 
80% in 90% of subjects. 
Safety Measures 
The proportion of participants that experience clinically significant 
skin irritation through 30 days of wear will be assessed through 
capture and reporting of all adverse events. 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 9 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
Additional Device Measures 
• 
Signal Artifact (%) – Defined as the proportion of ECG signal 
that is artifact over the wear duration, reported for each study 
device.  
• 
Device Functionality (%)  – Defined as the proportion of Zio 
monitors recording a continuous ECG signal through 21 days, 
and through 30 days. 
Other Measures 
Observational assessment of participant skin types that will be 
reported include: 
• 
Participant Skin Type – Dry, Oily, Normal (Baseline only) 
• 
Known Hyperhidrosis Status – Primary, Secondary or None 
(Baseline only) 
• 
Fitzpatrick Skin Type (Baseline only) 
• 
Chest Hair Density – e.g., smooth/no hair, some hair, 
moderately hairy, or very hairy (Baseline and follow-up) in the 
target patch placement area 
Participant Visits 
On-location visits are planned for Baseline (time of patch application), 
21 days, and 30 days following patch application. 
 
Telephone/video calls to the participants are planned for 7-day and 14-
day visits. 
Inclusion Criteria 
1. Participant must be 18 years or older at time of informed consent. 
2. Participant is willing and able to provide informed consent and be 
able to complete all visits for the study. 
Exclusion Criteria 
1. Participant has a known allergy to adhesives. 
2. Participant has a current skin infection or injury at location for study 
device placement. 
3. Participant is a member of a vulnerable population. 
4. Participant is a current or prior employee of iRhythm.  
5. Participant is unable or unwilling to participate or comply with study 
protocol. 
6. The local Investigator deems the participant has a condition that 
could limit the participant’s ability or willingness to participate in 
the study, or ability to comply with study required procedures 
and/or follow-up visits. 
7. Participant has experienced symptomatic episodes where instance 
variations in cardiac performance could result in immediate danger 
to the participant. 
8. Participant has an external cardiac defibrillator or may be exposed 
to high frequency surgical equipment near strong magnetic fields 
or devices such as MRI during the wear period. 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 10 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
¹The study device includes the wearable ECG adhesive assembly and symptom button common to both the Zio monitor and next generation 
Zio AT (Zio MCT) ambulatory cardiac monitoring devices.  The gateway associated with Zio MCT necessary for transmission of ECG data during 
device wear will not be included as part of this study.  For simplicity, the study device will be referred to Zio monitor within this protocol.  
Additional information regarding the study device is included in Section 2.3. 
 
9. Participant has a neuro-stimulator, as it may disrupt the quality of 
ECG data. 
10. Participant does not have the competency to wear the device for 
the prescribed monitoring period. 
11. Participant does not have the ability to consent for themselves (i.e., 
no LARs). 
Analysis Populations 
All analyses will be performed on the population of enrolled participants 
on whom the Zio monitor application was attempted.  The age, sex at 
birth, and application type (HCP designee vs. self-application) of 
participants will be monitored throughout the enrollment period to 
ensure representation across key user groups. 
 
Performance within subgroups including (but not limited to) sex at birth, 
age, and application type will be assessed. 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 11 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
1.0 
INTRODUCTION 
1.1 
Study Design 
This study is a prospective, multi-center, single-arm study to validate the design of the Zio® monitor2/Zio 
MCT® device form factor in extended (21-day) wear.  
1.2 
Study Objectives 
The objective of the study is to evaluate the wear performance of the Zio monitor device in a 
representative population over an extended wear period (of up to 30 continuous days) utilizing an 
updated skin preparation process to demonstrate that the device can be worn with adequate patch 
adherence and signal quality through 21 days. Assessment of wear performance will include evaluation 
of the wear duration of the patch and percentage of analyzable electrocardiographic time.  Product safety 
will be assessed by collection of all adverse events. 
2.0 
BACKGROUND AND RATIONALE 
Patients who are suspected of suffering from an arrhythmia-related condition typically undergo 
electrocardiography (ECG) monitoring.  Clinical symptoms associated with arrhythmia may include 
palpitations, shortness of breath, dizziness, lightheadedness, pre-syncope, syncope, or anxiety. 
Arrhythmias may also present asymptomatically.  Arrhythmias often occur infrequently and may not be 
detected with in-clinic 12-lead ECG monitoring (which records 10 seconds of data), or traditional 
ambulatory monitoring (i.e., with a Holter device up to 48 hours).  Long-term 14-day continuous 
ambulatory ECG monitoring is useful for the detection of infrequent arrhythmic events [1], though further 
extending the monitoring period may aid in detection of additional arrhythmias and provide additional 
clinical insights.  
The Zio monitor (K202359) received FDA 510(k) clearance on May 21, 2021 and is a long-term 
continuous ambulatory patch ECG monitor which adheres to the patient’s left pectoral region.  Additional 
description of the device is provided in Table 1.  The Zio monitor is substantially equivalent to the 
predicate Zio XT device but is designed to be smaller and more than 50% lighter.   
The Zio monitor is breathable with a waterproof housing³, and a more flexible design for a secure 
attachment.  These refinements allow for a more comfortable wear experience [2] with longer wear times 
and, therefore, provide more complete diagnostic data [3].  
Like the predicate Zio XT device, Zio monitor is currently indicated for long-term continuous monitoring of 
up to 14 days.  However, successful performance verification testing at iRhythm has demonstrated that 
the Zio monitor is capable of recording continuous ECG data for up to 21 days. 
This extended wear clinical design validation study will assess the extended wear performance of the Zio 
monitor device, by having participants wear the device for as long as possible (up to 30 days)   following 
an updated skin preparation process. 
 
2The study device includes the wearable ECG adhesive assembly and symptom button common to both the Zio monitor and next generation Zio 
AT (Zio MCT) ambulatory cardiac monitoring devices.  The gateway associated with Zio MCT necessary for transmission of ECG data during device 
wear will not be included as part of this study.  For simplicity, the study device will be referred to Zio monitor within this protocol.  Additional 
information regarding the study device is included in Section 2.3. 
3The Zio monitor device should not be submerged in water. During a bath, keep the device above water. Please refer to the Zio monitor application 
instructions for the full set of details. 
 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 12 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
Additionally, the percentage of analyzable ECG signal (i.e., percent analyzable time) will be assessed 
against a performance benchmark of 80%.  The device tested in this extended wear study will be the 
design cleared in K202359, with minor improvements for manufacturability and with the programming 
configurations updated to allow for continuous ECG data recording for up to 30 days.  Performance 
objectives include a mean wear time of at least 21 days, and percent analyzable time (i.e., artifact-free 
ECG signal) greater than 80% for at least 90% of study participants. 
2.1 
Name of the Device 
The device to be tested is the modified Zio® monitor (iRhythm Technologies, Inc., San Francisco, CA), 
inventory part number DFG0001, or equivalent.   
2.2 
Intended Indication for Use 
The Zio monitor is a prescription-only, single-patient-use ECG monitor that continuously records data for 
up to 14 days. It is indicated for use on patients who may be asymptomatic or who may suffer from 
transient symptoms such as palpitations, shortness of breath, dizziness, lightheadedness, pre-syncope, 
syncope, fatigue or anxiety.   
In this extended wear clinical study, the Zio monitor is being evaluated in participants who will wear the 
device for up to 30 days, in order to achieve a mean wear time of greater than 21 days. 
2.3 
Description of the Device 
The Zio monitor is a non-sterile, single-patient-use ECG monitor and recorder that provides a continuous, 
single-channel recording, and is substantially equivalent to the predicate commercial Zio XT Patch 
(K121319).  The device is FDA cleared to be marketed commercially for recording of up to 14 days.  See 
“Table 1: Device Comparison” for additional details. The predicate Zio XT device has been the subject of 
extensive clinical study.  Findings have demonstrated improved diagnostic yield as compared to 24-48 
Holter monitoring [4-7] and other ambulatory monitoring modalities [8]. 
The patch will be applied to the upper left pectoral region and activated by either the patient at home or 
in the clinic by a trained health care provider. Once activated, the Zio monitor records ECG data without 
patient interaction, with the goal of improving patient compliance via simplicity of operation.  There is a 
surface LED light that blinks to indicate proper activation and that the device is working or to indicate 
loss of connection with the skin or the presence of error conditions. 
When applied, the device provides continuous, single-channel ECG recording into memory without patient 
interaction for the duration of the prescribed monitoring. The Zio monitor features an embedded real-
time clock (RTC) for reporting purposes.  The RTC is initialized at the manufacturing facility and requires 
no patient or user interaction.  ECG data are acquired via electrodes mounted on the underside – the 
skin contact side – of the patch.  Data are sampled with an analog/digital converter (ADC), and 
subsequently saved to the onboard memory.  Stored ECG data are recorded into non-volatile memory, so 
data will not be lost in the event of power supply failure or battery expiry.  
There is a button on the surface of the patch, which may be pressed by the patient to indicate when he 
or she is experiencing a symptom. This button press is logged by software into a secondary data stream, 
where event time is noted. Recording continues without interruption. 
During normal operation, the device dynamically adjusts the input signal gain to a level that will maximize 
usage of ADC dynamic range and improve digital resolution of the recorded ECG signal, thereby improving 
the fidelity and contributing to improved interpretation results, particularly in situations of low-amplitude 
input signals. 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 13 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
At the conclusion of the wear period, the Study Staff or participant will remove the patch using the 
supplied materials and return it to the Sponsor. Once received, the recorded data will be downloaded for 
analysis by the Sponsor. The recorded ECG data are processed for detection of arrhythmias using an FDA-
cleared (K222389) set of artificial intelligence algorithms [9] combined with trained cardiac technician 
review to generate a preliminary report describing rhythm findings.   
Table 1: Device Comparison (Substantial Equivalence Summary) 
Feature 
Predicate Commercial Device: 
Zio® XT Patch (K121319) 
Study Device: 
Zio® monitor (K202359) 
Indications for Use 
Indications for Use Statements 
The Zio® Patch is a prescription-only, single-
patient-use, 
continuously 
recording 
ECG 
monitor that can be worn up to 14 days. It is 
indicated for use on patients who may be 
asymptomatic or who may suffer from 
transient symptoms such as palpitations, 
shortness 
of 
breath, 
dizziness, 
light-
headedness, presyncope, syncope, fatigue, or 
anxiety. 
The Zio® monitor is a prescription-only, single-
patient-use ECG monitor that continuously records 
data for up to 14 days. It is indicated for use on 
patients who may be asymptomatic or who  
may suffer from transient symptoms such as 
palpitations, shortness of breath, dizziness, 
lightheadedness, pre-syncope, syncope, fatigue or 
anxiety. 
General Characteristics  
Classification 
Class II:  21CFR870.2800 
Same 
Product Code 
DSH 
Same 
Patient Environment 
Ambulatory 
Same 
Patient Population 
Non-pediatric, non-critical care patients 
Same 
Programmed ECG Storage 
Duration  
14 days 
Up to 30 days 
Technological Characteristics  
Event Trigger 
Manually by patient 
Same 
Size 
The Zio Monitor has a reduced form factor 
Performance Characteristics  
 
Weight 
24.7 g 
10.0 g 
Dimensions 
5.2 x 2.0 x 0.5 in 
5.5 x 2.2 x 0.4 in 
Photograph or Drawing 
 
 
 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 14 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
Feature 
Predicate Commercial Device: 
Zio® XT Patch (K121319) 
Study Device: 
Zio® monitor (K202359) 
 
Zio XT (K121319) 
 
Zio® monitor (K202359) 
 
In addition to the Zio monitor and Zio XT long-term continuous ambulatory ECG monitors, a mobile cardiac 
telemetry device, Zio® MCT, is currently in development.  Zio MCT will leverage the same patch ECG form 
factor and end-of-wear ECG review as Zio monitor, but also enables transmission and review of 
symptomatic or auto-triggered events during the wear period.  Zio MCT-specific features, including auto-
detection and event transmission during wear will not be enabled nor evaluated as part of this study.  
However, this assessment of extended wear performance is applicable to both Zio monitor and Zio MCT 
as the patch devices share the identical electrical, mechanical, and adhesive assembly.  The main 
difference in the patch design is the firmware and the activation of the Bluetooth communication to the 
Gateway.  This is not expected to impact wear duration on Zio MCT as it is not adding weight or changing 
adhesive area vs Zio Monitor. 
The gateway which enables transmissions will not be included in this study. 
2.4 
Number of Participants 
A total of up to 150 participants will be enrolled in this study. Seventy-five participants have already been 
enrolled in the first phase of this study which utilized the iRhythm legacy skin preparation process. An 
additional 75 participants will be enrolled utilizing an updated skin prep process detailed in Section 5.1. 
2.5 
Overall Flow of the Study and Follow-up Schedule 
Figure 1 shows the overall flow of the study.  Participants who meet all inclusion and no exclusion criteria 
are eligible for enrollment into the study.  Study visits will be performed in-clinic (Baseline, 21-day and 
30-day) and by telephone or video (7- and 14-day).   
Participants must read, understand, and sign (by hand) the study Informed Consent Form prior to the 
initiation of the Baseline assessment visit and start of device wear.  Once consented, participants will 
have a study device applied to their chest by a Study Staff member or be provided a study device to self-
apply (i.e., simulated at-home patch application) on-site.  Study devices must be applied no later than the 
expiration date indicated on the kit.  Participants will be considered enrolled after they have signed the 
Informed Consent Form and attempted patch application has occurred.  Attempted patch application is 
defined as the opening of the patch kit and initiation of the shaving step necessary for skin preparation. 
During the wear period, participants will be contacted by phone or video call to determine adverse events 
and remind them of their next visit. Enrolled participants will undergo clinical evaluation at Baseline and 
21 days and 30 days after on-site or simulated at-home patch application. They will also be provided a 
contact number to report any adverse events that occur between planned visits. 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 15 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
 
 
Important Notes: 
1. Participants will be considered enrolled after they have signed the Informed Consent Form and have 
attempted to apply the patch.   
Candidate participant 
meets all inclusion and  
no exclusion criteria? 
Participant does not 
qualify for the study 
30-Day Follow-Up Visit (+ 3 days) 
•
Assess device condition (photo) 
•
Assess for any Adverse Event 
•
Remove device 
•
Skin Assessment (photo) 
Device Analysis 
•
ECG data from device are downloaded for endpoint analyses 
21-Day Follow-Up Visit (+ 3 days) 
•
Assess device condition (photo) 
•
Assess for any Adverse Event 
•
Schedule final visit 
14-Day Follow-Up Phone/Video Visit (+ 3 days) 
•
Assess device condition 
•
Assess for any Adverse Event 
•
Schedule next visit 
7-Day Follow-Up Phone/Video Visit (+ 3 days) 
•
Assess device condition 
•
Assess for any Adverse Event 
•
Schedule next visit 
Baseline Visit 
•
Eligibility is confirmed 
•
Participant reviews and signs the Informed Consent Form 
after all questions are answered 
•
Baseline assessments are performed 
•
Device is applied to begin study device wear (photo) 
•
Schedule next visit 
Figure 1: Overall Study Flow 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 16 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
2. Follow-up visits are conducted at the indicated days following application of the patch, whether in clinic 
or by phone/video call. 
3. Early patch detachment and/or completion of the 30-day visit also includes a study completion form. 
4. Photos are to be taken at Baseline before and after application, at the 21-day visit of the device, at the 
30-day visit of the device both on and off the participant as well as a photo of the skin at the location 
the patch was worn. Optionally, photos may also be taken at the 7-day and/or 14-day visits if they occur 
via video call. 
2.5.1 
Study Safety Committee 
A study safety committee will meet as needed to assess any safety events that may occur.  The study 
safety committee meetings will be conducted according to a separate charter.  The charter will include 
meeting scope, roles and activity specifics. 
3.0 
STUDY PERFORMANCE OBJECTIVES AND ADDITIONAL MEASURES 
3.1 
Wear Time Performance Objective 
Wear duration is defined as the number of days the patch is attached to the participant.  Wear duration 
measurement will start at the time of device application and will end at any of the following events: 
• 
the device is removed at the 30-day follow-up visit, or 
• 
the device fails to adequately adhere to the skin. 
All enrolled participants on whom patch application was attempted will be included as part of the mean 
wear duration analysis. However, participants who discontinue wear of the device for reasons outside of 
the study protocol, or occurrence of an adverse event not related to the study, will not be counted in the 
analysis. Full disclosure for reasons of discontinuation will be provided in the study report. 
Mean wear duration will be compared to a performance goal of 21 days. The performance objectives 
will be met if the mean wear duration is greater than 21 days. 
3.2 
Analyzable Time Performance Objective 
Analyzable time is the percentage of time during the wear of the Zio monitor device which yields 
analyzable ECG signal (i.e., free from signal artifact).   
All enrolled participants in whom patch application was attempted will be included as part of the 
percent analyzable time analysis. However, participants who discontinue wear of the device for reasons 
outside of the study protocol, or occurrence of an adverse event not related to the study, will not be 
counted in the analysis. Full disclosure for reasons of discontinuation will be provided in the study 
report. 
Percent analyzable time will be compared to a performance objective of 80%. The performance 
objective will be met if the percent analyzable time is greater than 80% in 90% of subjects.  
3.3 
Safety Measures 
All enrolled participants on whom patch application was attempted will be included in the safety 
analysis.  The proportion of participants that experience clinically significant skin irritation through 30 
days of wear will be assessed.  
• 
Reaction severity will be assessed and reported, as follows [10]: 
o Weak Positive Reaction:  Presence of erythema infiltration, discrete papules 
o Strong Positive Reaction:  Presence of erythema infiltration, papules, discrete vesicles 
o Extreme Positive Reaction:  Presence of bullous or ulcerative reaction, coalescing 
vesicles 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 17 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
An ‘Extreme Positive Reaction’ will be considered a clinically significant skin irritation. 
Any skin reaction should be reported as an adverse event. Skin reactions are anticipated (see Section 
12.2). All adverse events will be reviewed by a physician on the safety committee. 
3.4 
Additional Device Measures 
• 
Signal Artifact (%) – Defined as the proportion of ECG signal that is artifact over the wear duration, 
reported for each study device. 
• 
Device Functionality (%) – Defined as the proportion of Zio monitors recording a continuous ECG 
signal for (1) 21 days, and (2) for 30 days.  
3.5 
Other Measures 
Observational assessment⁸ of participant skin types that will be reported include: 
• 
Participant Skin Type – Dry, Oily, Normal (Baseline only) 
• 
Known Hyperhidrosis Status – Primary, Secondary or None (Baseline only) 
• 
Fitzpatrick Skin Type -Type I-VI (Baseline only) 
• 
Chest Hair Density – e.g., smooth/no hair, some hair, moderately hairy, or very hairy (baseline 
and follow-up) in the target patch placement area 
4.0 
PARTICIPANT SELECTION AND WITHDRAWAL  
4.1 
Participant Recruitment Population and Retention 
A study population representative of the intended population and who meet the study eligibility criteria 
will be approached for participation.  iRhythm may utilize a recruitment firm such as FieldWork® or 
community clinics who are qualified by experience and able to support this study.  
The clinics and FieldWork may utilize email solicitation, social media posting, review of their current 
research database of potential participants and/or flyer posting with prior approval by the IRB.  
Recruitment of at least 61 participants will be needed, and enrollment may continue up to a total of 75 
participants for each of the two (2) phases. Seventy-five participants have already been enrolled in the 
first phase of this study which utilized the iRhythm legacy skin preparation process. An additional 75 
participants will be enrolled utilizing an updated skin prep process. Therefore, up to 150 participants will 
be enrolled. 
To ensure recruitment of a population representative of patients undergoing long-term continuous 
monitoring, age, gender, and in-clinic HCP designee vs. self-application (i.e., simulated at-home patch 
application) will be tracked by the study team. The following represent enrollment targets across these 
key groups: 
• 
Approximately 1/3 of participants <51 years of age 
• 
Approximately 1/3 of participants ≥51 and <70 years of age 
• 
Approximately 1/3 of participants ≥70 years of age 
• 
At least 40% of participants should be female 
• 
Devices are self-applied for approximately 1/3 of the study population.  
4.2 
Participant Screening and Informed Consent 
Informed consent will be obtained in-person, in the clinic. Participant screening may be performed in-
person, by telephone, or by videotelephony (e.g., Zoom).  
⁸See Appendix II for assessment definitions. 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 18 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
 
4.2.1 
Participant Screening 
A recruitment firm (FieldWork or similar) will be utilized for initial screening. Participants who have been 
identified by the recruitment firm will be seen at one of two Sponsor locations (San Francisco, CA or  
Deerfield, IL), the Investigator or research staff, who have been trained to the Protocol, will verify all 
participants meet all inclusion and no exclusion criteria to determine if the potential participant is eligible 
for study enrollment.   
Potential participants will be assigned a screening number (assigned sequentially/chronologically).  An 
accurate and up-to-date screening log of all participants considered for the trial will be maintained at 
each study location.  The result of the participant screening process shall be documented in the screening 
log to include presentation route, whether the participant met eligibility criteria (and if not, which eligibility 
criteria were not met), and whether the participant was subsequently enrolled.   
4.2.2 
Informed Consent 
The Study and the Study Informed Consent Form (ICF) must receive approval by an independent IRB prior 
to beginning enrollment into the Study. The central IRB for this study is Advarra. 
During the informed consent process, the Investigator or designee, who has been trained on the Protocol, 
will explain the nature and scope of the trial, potential risks and benefits of participation, and answer 
questions from potential participants.   
All participants must sign and date the IRB-approved Informed Consent Form prior to any trial-specific 
procedures.  Those who are not able to provide consent on their own will not be enrolled.  Obtaining the 
consent, provision of copy to the participant, along with date and time must be documented in the 
participant’s source documents.  
The Informed Consent Form must also be signed by the investigator or designee. The Investigator or 
designee is responsible for advising the participant of any new information about the study or the study 
device(s) that may become known during the study.  The consent will be administered by paper.  
An authorization for use and disclosure of the participant’s protected health information, in accordance 
with the Health Insurance Portability and Accountability Act (HIPAA), must be obtained from the 
participant. The requirements of HIPAA elements may be incorporated into the Informed Consent Form 
or it may exist as a standalone document. 
4.2.3 
Disclosure of Participant Personal Contact Information 
In order to conduct a phone or video visit, or to follow-up regarding study-related activities with the 
participant, the study team at iRhythm will collect the participant’s phone number and email.  The 
participant’s identity will be anonymized to the extent possible.  Only those iRhythm Study Staff individuals 
who are directly involved with the study will have access to the participant’s protected health information 
(PHI) for those individuals enrolled through the iRhythm clinics.  
4.3 
Eligibility Criteria 
Participants shall be screened per the criteria listed below.  Assessment for eligibility criteria will be 
completed through an interview with a potential participant. Participants must meet ALL of the inclusion 
criteria to be considered for the study. If ANY of the exclusion criteria are met, the participant is excluded 
from the study.  Participants meeting these criteria will be approached to provide informed consent for 
participation in the Study and included on the screening log. 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 19 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
4.3.1 
Inclusion Criteria 
Participants must meet all of the following inclusion criteria in order to participate in the study: 
1. Participant must be 18 years or older at time of informed consent.  
2. Participant is willing and able to provide informed consent and able to complete all visits for this 
study. 
4.3.2 
Exclusion Criteria 
Participants who meet any of the following exclusion criteria may not participate in the study: 
1. Participant has a known allergy to adhesives. 
2. Participant has a current skin infection or injury at location for study device placement. 
3. Participant is a member of a vulnerable population. 
4. Participant is a current or prior employee of iRhythm. 
5. Participant is unable or unwilling to participate or comply with study protocol. 
6. The local Investigator deems the participant has a condition that could limit their ability or 
willingness to participate in the study, or ability to comply with study required procedures and/or 
follow-up visits. 
7. Participant has experienced symptomatic episodes where instance variations in cardiac 
performance could result in immediate danger to the participant. 
8. Participant has an external cardiac defibrillator or may be exposed to high frequency surgical 
equipment near strong magnetic fields or devices such as MRI during the wear period. 
9. Participant has a neuro-stimulator, as it may disrupt the quality of ECG data. 
10. Participant does not have the competency to wear the device for the prescribed monitoring period. 
11. Participant does not have the ability to consent for themselves (i.e., no LARs). 
4.4 
Participant Enrollment and Inclusion  
Participants are considered enrolled after they have signed the Informed Consent Form and patch 
application has been attempted.  Attempted patch application is defined as the opening of the Patch kit 
and initiation of the first step necessary for skin preparation. 
Enrolled participants on whom patch application is attempted will be included in the analysis population. 
Consistent with recent FDA guidance on increasing diversity in clinical trial enrollment (Enhancing the 
Diversity of Clinical Trial Populations – Eligibility Criteria, Enrollment Practices, and Trial Designs:  
Guidance for Industry, Issued November 2020), iRhythm will attempt to implement measures to ensure 
that the study population reflects the characteristics of clinically relevant population. Section 4.1 above 
describes measures taken to ensure enrollment of a relevant population with respect to age, sex and 
device application (in-clinic or self-application).   
In addition, diversity across races and ethnic groups will be considered in selection of study sites and 
through recruitment activities. The study intends to enroll a diverse group of participants representative 
of the US population at large. 
4.5 
Participant Payment  
Participants who meet eligibility and are enrolled in the study may be eligible to receive a stipend.  The 
recruitment firm will manage all activities for payments including reporting of the payments to the Internal 
Revenue Service, if required.  
The amount of the participant stipend will be included in the Informed Consent Form and approved by 
the IRB.   
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 20 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
4.6 
Participant Discontinuation 
Participants shall remain in the study until completion of the required follow-up period, unless the device 
experiences early detachment. The participant’s involvement in any clinical study is voluntary and the 
participant has the right to withdraw at any time without penalty or loss of benefit. Conceivable reasons 
for discontinuation may include, but are not limited to, the following: 
• 
Participant death 
• 
Participant voluntary withdrawal  
• 
Participant withdrawal by physician as clinically-indicated 
• 
Participant lost-to follow-up as described below.  
The Sponsor Study Staff must be notified of the reason(s) for participant discontinuation. Study staff are 
required to report this to the central IRB as defined by the IRB’s requirements.  
No additional follow-up will be required or data recorded from participants once withdrawn, except for the 
status (deceased/alive). 
4.6.1 Lost-to-Follow-up: 
If the participant misses the scheduled follow-up time point and the attempts at contacting the participant 
detailed below are unsuccessful, then the participant is considered lost to follow-up. Study personnel 
shall make all reasonable efforts to locate and communicate with the participant (and document these 
efforts in the source documents), including the following, at each contact time point: 
• 
A minimum of 2 telephone calls or emails on different days over a 10-day period to contact the 
participant should be recorded in the source documentation, including date, time and initials of 
study personnel trying to make contact. 
• 
If these attempts are unsuccessful, a certified letter should be sent to the participant.  The letter 
will request the participant to contact the Investigator. Study staff will also request return of the 
Zio monitor to iRhythm as soon as possible.  
4.7 
Number of Participants Required to be Included in the Study 
A total of up to 150 participants will be included in the study. 
4.8 
Estimated Time Needed to Enroll this Number  
It is anticipated that it may take up to 16 weeks to enroll all required participants.   
4.9 
Expected Duration of Each Participant’s Role 
The expected duration of participation is approximately 30 days.   
4.10 
Total Expected Duration of the Study 
The time to complete the Study is estimated to be approximately six months (four months to complete 
participant enrollment, one month follow-up and one month to complete analysis and generate the study 
report).   
4.11 
Study Participant Completion 
A participant is considered to have completed the study when any of the following has occurred: 
• 
The participant is considered lost to follow-up per the above definition  
• 
The participant withdraws consent 
• 
The Investigator withdraws the participant from the Study  
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 21 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
• 
The participant has died  
• 
The Study has been completed (e.g., the participant’s 30-day or final follow-up time point has 
been reached)  
• 
The patch has prematurely detached from the participant (in the case of early detachment the 
participant should notify study staff of the date and time of detachment, and a study completion 
visit will be scheduled)      
• 
The Sponsor has terminated the Study. 
Sponsor must be notified of the reason for participant discontinuation.  Investigators must also report 
this to their IRB, as required. Participants will not be replaced. 
5.0 
BASELINE VISIT AND FOLLOW-UP ASSESSMENTS 
5.1 
Baseline (Visit 1) 
During the Baseline visit (Visit 1) the participant will be consented, and the informed consent process will 
be documented prior to patch application. Additional activities include: 
Baseline health and demographic information: 
The following information will be gathered from each participant in order to establish representation of 
the population and includes minimum:  
• 
Medical Background/History as reported by the participant, including:  
- Cardiac Disease History 
▪ 
Including indication for monitoring if enrolled at a clinical care site 
- Skin characteristics as reported by the participant 
▪ 
Skin Type (e.g., dry, oily, or normal) 
▪ 
Hyperhidrosis Status (e.g., primary, secondary, or none – see definitions in appendix ) 
▪ 
Fitzpatrick Skin Type (e.g., Type I-VI) – using the Fitzpatrick Skin Type assessment 
questionnaire completed by the participant 
▪ 
Chest Hair Density by visual inspection (e.g., smooth/no hair, some hair, moderately 
hairy, or very hairy) in the target patch placement area 
• 
Demographic Information 
 
- 
Age 
- 
Sex at birth 
- 
Race 
- 
Ethnicity 
- 
Weight 
- 
Height 
 
Patch application: 
The Zio monitor will be applied to the participant’s left upper chest/pectoral region and may be completed 
by either the participant (self-application) or by a Health Care Provider (HCP) or designee (i.e., the Study 
Coordinator or cardiac technician). There are two phases to this study. The application process for the 
first 75 study participants was conducted as outlined in the Zio Monitor Instructions for Use – LB10262.A. 
All 75 study participants have been enrolled as of 28 February 2025. Phase two of enrollment will include 
an additional 75 study participants using an updated skin prep process, the formal labeling instructions 
are not yet finalized pending the outcome of this study, but the following steps will be utilized in phase 
two: 
▪ 
Identify the area of skin to be prepared for application. 
▪ 
Shave the area for all genders even if there is no visible hair present.  
• 
Proceed with shaving 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 22 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
• 
Wipe away the hair shavings  
• 
Make sure the skin is dry before continuing 
▪ 
Exfoliate the area with 20 strokes to remove dead skin. 
• 
10 strokes up and down, 10 strokes left to right 
• 
If discomfort occurs, decrease the pressure of the strokes 
▪ 
Clean the prepared skin with the alcohol wipe. 
▪ 
Wait one minute for the skin to dry. Study Staff to take a photo of the prepared skin 
▪ 
Proceed with applying the Zio monitor. 
▪ 
Study Staff to take a photo of the skin after the Zio monitor has been applied. 
During the Baseline visit, participants will either have a patch applied by a Study Staff member (i.e., Study 
Coordinator) or participants will self-apply the patch to simulate home enrollment. In the event of self-
application, the study participant will open the Zio monitor kit and the Zio monitor instructions for 
application and will self-apply the device in the presence of a Study Staff member. The Study Staff 
member is allowed to provide some guidance, but every effort should be made to allow the participant to 
place the patch without intervention from the Study Staff. 
If there is an issue with the device after initial placement (e.g., device fails to activate), the device will be 
removed and a 2nd device may be applied. In the case that a 2nd device is required, the shaving and 
exfoliation steps may be skipped, but the alcohol wipe and drying step will still be completed. 
5.2 
Patch Wear Period 
All consented participants in whom the Zio monitor Patch application is attempted will be considered 
enrolled in the study.  Patch application is considered to have been attempted when the Zio monitor Patch 
kit is opened and the first step necessary for skin preparation has been initiated.  The participant will be 
instructed to wear the device for as long as possible, up to the 30-day visit.   
Study participants will be instructed to press and hold along the edges of the patch if they notice the 
patch peeling or lifting at the edges during the wear period.  If a patch completely detaches from the 
participant’s chest, the patch will not be re-applied.  In the case of early patch detachment, the participant 
should notify study staff of the date and time of detachment, and a study completion visit should be 
scheduled as soon as possible.      
At any time after patch application, if the device is determined to no longer be functioning (for example, 
if a rapidly blinking orange light is observed), the device will not be replaced.  The date and time the 
determination of function failure will be noted as close to accurate as possible. As a non-functioning 
device does not present a safety concern, the participant will be asked to continue wearing the non-
functioning patch for as long as possible, in order to record wear duration and wear experience data.   
5.3 
Protocol Required Medications 
There are no protocol required medications for this study, and no medications will be administered for 
the study. A complete list of current medications will not be requested during the Baseline visit. However, 
medications used to treat an adverse event will be captured.  
5.4 
7-Day and 14-Day (+ 3 days) Participant (Phone Call or Video Visit 2 & 3) 
A phone call or video call at days 7 and 14 will be conducted in order to assess the status of the 
participant and the patch adherence.  
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 23 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
5.5 
21-Day (+3 days) Participant Follow-up (Visit 4) 
At day 21 following patch application and up to day 24, participants will be asked to return to the clinic 
and the following activities will be conducted: 
- 
Skin assessment by HCP or designee, including photograph of the area of the device 
- 
Adverse Event review 
- 
Answering of any questions and verification of ongoing consent to study participation  
5.6 
30-Day (±3 days) Participant Follow-up (Visit 5) 
At day 30 following patch application and up to day 33, participants will be asked to return to the clinic 
and the following activities will be conducted: 
- 
Skin assessment by HCP or designee, including photograph of the area with the device on and also 
upon device removal 
- 
Adverse Event review 
- 
Zio patch removal and visual inspection, including photograph of front and back of patch 
- 
Patch return to iRhythm Technologies, Inc. for data download and evaluation 
 
Participants who applied the Zio to themselves at the Baseline visit will be asked to remove the patch. 
They may ask a Study Staff member to provide guidance in the removal process.  
Study clinical assessments and activities are summarized in Table 2. 
 
 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 24 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
 
Table 2: Clinical Assessment Schedule 
Required Assessments to be Collected 
Baseline 
(Visit 1) 
7 & 14-Day 
(Visit 2 & 3) 
21-Day 
(Visit 4) 
30-Day 
(Visit 5) 
±3 days 
Phone or 
Video Call 
only 
+3 days 
+3 days  
Informed Consent1 
X 
X 
- 
- 
Medical and Cardiac Background/History 
X 
- 
- 
- 
Fitzpatrick Skin Assessment 
X 
- 
- 
- 
Skin Condition Assessment2, Including 
photograph(s) 
X 
- 
X 
X 
Assessment of Device Adhesion 
Performance, Including photograph(s) 
- 
- 
X 
X 
Adverse Events3 
X4 
X 
X 
X 
1. Continued Informed Consent will be verified at each post-baseline contact.  
2. Including chest hair density, as applicable. 
3. Adverse Events include serious adverse events, all device-related complications, device deficiencies, 
device malfunctions, procedures and any hospitalizations. If AEs are ongoing at the 30-day visit, the 
participant should be contacted until resolution, or Day 37, whichever is sooner. 
4. AEs are only assessed following Informed Consent and participant enrollment into the study. 
The study device will be returned to iRhythm Technologies, Inc. for download and analysis of the ECG 
signal collected during the wear.   
Upon completion of study follow-up, all devices will be retrieved from study participants and returned to 
the Sponsor for analysis. Devices will be processed through the algorithm and reviewed by a clinical 
research qualified cardiac technician. The preliminary report will be provided to a Safety Committee and 
reviewed by a licensed cardiologist for finalization and determination of any safety concerns. A copy of 
the report will also be provided to the participant for their medical records and to share with their personal 
physicians. 
NOTE: Following data retrieval from the Zio patch, the patch will be provided to Research & Development 
(R & D) for further review and inspection. Any reporting from potential findings from the device inspection 
by R & D is separate from this study protocol and out of scope. 
6.0 
ADVERSE EVENTS 
Adverse events will be monitored and reviewed with the Study Investigator to determine any necessary 
action.  To comply with standards and guidelines on clinical study adverse event reporting, the following 
standard definitions and reporting timelines will be adhered to for this study.  
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 25 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
6.1 
Definitions 
6.1.1 
Adverse Event 
An adverse event (AE) is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in participants, users or other persons, whether or 
not related to the medical device. It is anticipated that arrhythmias will be noted on the scans. These are 
not considered adverse events and do not require reporting unless they have caused an adverse event 
(i.e., rapid atrial fibrillation is noted on scan, during this time the subject had a syncopal episode that 
resulted in bruising. The atrial fibrillation is not the AE but the syncopal episode is an AE and must be 
reported). 
For this study AEs will be defined as follows:  
• 
Mild:  Transient or mild discomfort; no limitation in activity; no medical intervention/therapy 
required. 
• 
Moderate:  Mild-to-moderate limitation in activity, some assistance may be needed; no or minimal 
medical intervention/therapy required. 
• 
Severe:  Marked limitation in activity, some assistance usually required; medical 
intervention/therapy required, hospitalizations possible. 
• 
Life-threatening:  Extreme limitation in activity, significant assistance required; significant medical 
intervention/therapy required hospitalization or hospice care probable. 
6.1.2 
Serious Adverse Event 
If the AE meets any of the criteria below, it is regarded as a serious adverse event (SAE) and is required 
to be reported according to the FDA guidelines for SAE reporting.  
a) Led to a death, 
b) Led to a serious deterioration in health that either: 
1) Resulted in a life-threatening illness or injury, or 
2) Resulted in a permanent impairment of a body structure or a body function, or 
3) Required in-patient hospitalization or prolongation of existing hospitalization, or 
4) Resulted in medical or surgical intervention to prevent life threatening illness or injury or 
permanent impairment to a body structure or a body function. 
c) Led to fetal distress, fetal death or a congenital abnormality or birth defect. 
An important medical event that may not result in death, be life-threatening, or require hospitalization but 
may be considered serious when, based upon appropriate medical judgment, may jeopardize the 
participant and/or may require intervention to prevent one of the outcomes listed in this definition may 
also be considered an SAE. 
Note 1: This includes device deficiencies that might have led to a serious adverse event if a) suitable 
action had not been taken or b) intervention had not been made or c) if circumstances had been less 
fortunate. These are handled under the SAE reporting system. 
Note 2: A planned hospitalization for pre-existing condition, or a procedure required by the Clinical 
Protocol, without a serious deterioration in health, is not considered to be a serious adverse event. 
6.1.3 
Device Malfunction 
A device malfunction (DM) is the failure of a device to meet its performance specifications or otherwise 
perform as intended, when used in accordance with the IFU or protocol. 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 26 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
6.2 
Device, Process or Procedure Relationship 
Determination of whether there is a reasonable possibility that a product, process or procedure caused 
or contributed to an AE is to be determined by Study Staff and recorded on the appropriate CRF. 
Determination should be based on assessment of temporal relationships, evidence of alternative etiology, 
medical/biologic plausibility, and patient condition (pre-existing condition). 
6.2.1 
Unanticipated (Serious Adverse) Device Effect [U(S)ADE] 
Unanticipated serious adverse device effect (USADE) refers to any serious adverse effect on health or 
safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or degree of incidence in the protocol 
or application (including a supplementary plan or application), or any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or welfare of participants.  See Anticipated 
Device Effects (Section 12.2). 
6.3 
Adverse Event/Device Deficiency/Product Experience Reporting 
6.3.1 
Adverse Event Reporting  
Occurrences of adverse events will be monitored for each participant during the course of the study as 
required by this protocol, per AE and SAE definitions as noted in the sections above. 
All information must be entered in the Electronic Data Capture (EDC) system as soon as feasible. AEs 
need to be collected for consented participants on the appropriate AE CRF. Additional information with 
regards to an adverse event, including whether or not the event was anticipated, should be updated 
within the appropriate CRF and source records. 
Serious adverse events (SAEs) that occurred in the user or persons other than the study participant 
should not be entered in the CRF; they should be reported to researchstudies@irhythmtech.com.  Study 
staff will regularly monitor this email address and will investigate all events reported. These will be 
reported as soon as possible but no later than 3 calendar days from the day the study personnel became 
aware of the event. The SAE will be reported to the local IRB according to reporting requirements. 
6.3.2 
Unanticipated Serious Adverse Device Effect Reporting 
iRhythm (the Sponsor) is required to report and document any USADE as soon as possible, but at least 
within 24 hours of the Investigator’s knowledge of the event.  
6.3.3 
Device Deficiency/Device Malfunction Reporting 
All device deficiencies/malfunctions should be reported on the appropriate CRF no later than 3 calendar 
days from the day the study personnel became aware of the event or as per the investigative location’s 
local requirements, if the requirement is more stringent than those outlined. 
An email address (researchsupport@irhythmtech.com) will be made available to allow the Investigator to 
report device deficiencies/malfunctions. This does not replace the CRF. All information must still be 
entered in the CRF as soon as feasible.  Study staff will regularly monitor this email address and will 
investigate all events reported.  
In case a device deficiency/malfunction occurred before the patient ID has been assigned, the device 
deficiency should also be reported to iRhythm via researchsupport@irhythmtech.com.  
The device, if not applied or not remaining on the participant, should be returned to iRhythm Technologies, 
Inc. 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 27 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
Device deficiencies/malfunctions should be reported to the IRB per the investigative location’s local 
requirements and IRB requirements. 
6.3.4 
Adverse Event Reporting to Country Regulatory Authorities by the Sponsor 
Where required by local or regional requirements, the Sponsor will report the SAEs and DDs to the 
appropriate regulatory authority.  
7.0 
STATISTICAL ANALYSIS 
7.1 
Analysis Population 
Following the Phase I completion of all participant activities an analysis will be conducted. Separately, 
following the Phase II completion of all participant activities an analysis will be conducted. All analyses 
will be performed on the population of enrolled participants in whom patch application was attempted in 
that Phase. Phase 1 analysis is considered separate from Phase 2 and will be conducted and reported 
accordingly. Sections 7.2 and beyond (detailed below) will adhere to this plan.   
7.2 
Sample Size Calculations and Assumptions 
A prior study of 30 subjects instructed to wear the Zio monitor device up to 30 days resulted in a mean 
wear time of >24 days (24.9 ± 9.3 days).  
Therefore, a power analysis was performed using the following assumptions: 
• 
Performance goal:  > 21 days 
• 
Estimated wear duration with the Zio monitor patch:  24.0 days 
• 
Estimated standard deviation of wear duration with the Zio monitor patch:  9.3 days 
• 
Statistical test:  One sample t-test 
• 
Statistical Power:  80% 
• 
Significance level:  One-sided alpha = 0.05 
Given these assumptions, enrollment of 61 participants is required to assess performance of wear 
duration performance.   
SAS Enterprise Guide 8.3 was used for all calculations.  
In order to assess the frequency of adverse events with reasonable precision, and to account for the 
possibility that up to 25% of enrolled participants may not provide ECG data at the 30-day visit due to 
device removal or loss to follow-up, enrollment of up to 75 participants is planned for each of the two (2) 
phases. Seventy-five participants have already been enrolled in the first phase of this study which utilized 
the iRhythm legacy skin preparation process. An additional 75 participants will be enrolled utilizing an 
updated skin prep process. A total of 150 participants will be enrolled under this protocol 
7.3 
Planned Interim Analyses 
There is no planned interim analysis for this study. Each analysis will be considered the final analysis for 
that Phase of the study. 
7.4 
Statistical Analyses 
For wear duration performance, mean wear duration, standard deviation and 95% confidence interval 
will be reported.  For analyzable time performance, the mean percent analyzable time, standard 
deviation, 95% confidence interval, and percentage of patients with analyzable time >80% will be 
reported.  Performance objectives will be met if the mean wear duration is greater than 21 days, and 
percent analyzable time is greater than 80% in 90% of subjects. 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 28 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
For other analyses, mean and standard deviation or median, interquartile range, minimum and maximum 
will be reported for continuous variables; counts and percentages will be reported for categorical 
variables. 
7.4.1 
Subgroup Analysis 
Performance within subgroups including (but not limited to) sex, age, and application method (in-clinic 
HCP or designee vs. self-applied) will be assessed.  
8.0 
QUALITY CONTROL AND QUALITY ASSURANCE 
8.1 
Selection of Study Site Locations and Investigators 
iRhythm Technologies, Inc. will utilize two iRhythm locations for the recruitment firm’s referrals and 
participant enrollment. All Study Staff will be trained appropriately. Contract Study Coordinators will be 
utilized at these locations to decrease any biases. The primary Investigator of the study will also serve as 
the Principal Investigator at the iRhythm locations. 
Prior to receipt of study devices all locations must be trained to the protocol, the CRFs, and other 
appropriate study activities. All locations MUST have IRB approval to recruit and enroll participants. 
Good Clinical Practice certification is required for all study staff who will have direct contact with the study 
participants or their data. 
8.2 
Protocol Amendments 
The Sponsor will provide approved Protocol amendments to the Investigator(s) prior to implementing the 
amendment. The Principal Investigator is responsible for notifying the IRB or equivalent committee of the 
Protocol amendment (administrative changes) or obtaining IRB’s approval of the Protocol amendment 
(changes in participant care or safety), according to the instructions provided by the Sponsor with the 
Protocol amendment.   
Acknowledgement/approval by the IRB of the Protocol amendment must be documented in writing prior 
to implementation of the Protocol amendment. Copies of this documentation must also be provided to 
iRhythm Technologies, Inc. 
8.3 
Training 
8.3.1 
Study Training 
All Investigators/study personnel, designee, etc. are required to attend the study training sessions, which 
may be conducted at a sponsor location initiation visit (SIV) or other appropriate training sessions. Over-
the-phone, video ‘webinar’, or self-training to the study and/or the device may take place as needed. 
Training of Investigators/study personnel will include, but is not limited to, the Protocol requirements, 
device usage, electronic CRF completion and study personnel responsibilities.  
All Investigators/study personnel that are trained must sign a training log (or an equivalent) upon 
completion of the training. Prior to signing the training log, Investigator/study personnel must not perform 
any study-related activities that are not considered standard of care at the sponsor location. 
All study personnel who have been trained to the study must also be listed on the Delegation of Authority 
log provided by iRhythm. The log must be kept updated throughout the study. A final copy of the DOA log 
will be collected from each study center and location for filing in the TMF for the study.  
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 29 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
8.3.2 
Training of Sponsor’s Monitors 
Sponsor and/or designated study monitors will be trained to the Protocol, case report forms and device 
usage (as appropriate). Documentation of this training will be according to written procedures. 
8.4 
Monitoring 
Centralized monitoring will occur through routine internal data review. This monitoring is designed to 
identify missing and inconsistent data, data outliers, and potential Protocol deviations that may be 
indicative of non-compliance at the sponsor location. On-site monitoring may occur at the discretion of 
the Sponsor. 
Prior to initiating any procedure, the Sponsor monitor (or delegate) will ensure that the following criteria 
are met: 
• 
The Investigator understands and accepts the obligation to conduct the research study according 
to the Protocol and applicable regulations and has signed the Investigator Agreement or the 
Clinical Study Agreement. 
• 
The Investigator and his/her staff have sufficient time and facilities to conduct the study and that 
they have access to an adequate number of appropriate participants to conduct the study.  
• 
Source documentation (including original medical records, if applicable) must be available to 
substantiate proper informed consent procedures, adherence to Protocol procedures, training 
records and appropriate delegation of roles, adequate reporting and follow-up of adverse events, 
accuracy of data collected on case report forms, and device information.  
• 
If monitoring visits are scheduled, the Investigator/sponsor location will permit access to such 
records. A monitoring visit sign-in log will be maintained by study staff. The Investigator will agree 
to dedicate an adequate amount of time to the monitoring process. The Investigator and/or 
research coordinator will be available for monitoring visits. It is expected that the Investigator will 
provide the study monitor with a suitable working environment for review of study-related 
documents. 
8.5 
Deviations from Protocol 
The Investigator will ensure that the study does not deviate from the IRB approved Protocol for any reason 
without prior written approval from Sponsor except in cases of medical emergencies, when the deviation 
is necessary to protect the rights, safety and well-being of the participant or eliminate an apparent 
immediate hazard to the participant. In that event, the Investigator will notify Sponsor immediately by 
phone or in writing. All deviations must be reported to the Sponsor. In participant-specific deviations from 
the Protocol, a Protocol deviation case report form will be completed. The occurrence of Protocol 
deviations will be monitored by the Sponsor for evaluation of Investigator compliance to the Protocol and 
regulatory requirements and dealt with according to written procedures. Investigators will inform their IRB 
or equivalent committee of all Protocol deviations in accordance with their specific IRB or equivalent 
committee reporting policies and procedures.  
In the event of repeated non-compliance, as determined by the Sponsor, a Sponsor’s monitor or company 
representative will attempt to secure compliance by one or more of the following (and not limited to):  
• 
Visiting the Investigator and/or delegate 
• 
Telephoning the Investigator and/or delegate 
• 
Corresponding with the Investigator and/or delegate 
Repeated non-compliance with the signed agreement, the Protocol or any other conditions of the study 
may result in further escalation in accordance with the Sponsor’s written procedures including securing 
compliance or, at its sole discretion; Sponsor may terminate the Investigator's participation in the study.  
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 30 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
8.6 
Quality Assurance Audit 
A Sponsor representative or designee may request access to all clinical study records, including source 
documentation, for inspection and duplication during a Quality Assurance audit.  
In the event that an Investigator is contacted by a Regulatory Agency in relation to this clinical study, the 
Investigator will notify the Sponsor immediately. The Investigator and Research Coordinator must be 
available to respond to reasonable requests and audit queries made during the audit process. The 
Investigator must provide the Sponsor with copies of all correspondence that may affect the review of the 
current clinical study (e.g., Form FDA 483, Inspectional Observations, Warning Letters, Inspection Reports, 
etc.). Sponsor may provide any needed assistance in responding to regulatory audits. 
9.0 
DATA HANDLING AND RECORD KEEPING 
All CRF data collection will be performed by authorized personnel to enter, review or correct data in a 
secure EDC System. Access will be strictly confidential. 
For the clinical study duration, the Investigator will maintain complete and accurate documentation 
including, but not limited to, source documents, clinical study progress records, electronic case report 
forms, signed ICFs, device accountability records, correspondence with the IRB and clinical study 
monitor/Sponsor, adverse event reports, and information regarding participant discontinuation or 
completion of the clinical study.  Protocol deviations are not anticipated, but if they occur, they will be 
recorded in the EDC System.  All study related documents will be stored in a secured location. 
The handling, storage, transfer and destruction of the data will comply with all applicable national and 
local laws. 
The following persons will have access to identifiable data in order to review and ensure the Study is run 
appropriately: the Sponsor representatives (such as contract monitors or study managers) visiting the 
study sponsor location, the Study Staff participating and running the Study, regulatory (i.e., FDA) and 
health authorities.  Participants consenting to participate will allow these persons to read the identifiable 
information. 
The Sponsor (including persons working under the Sponsor) will have access to de-identified data only.  
The Sponsor will take reasonable measures to keep the data confidential and secure. 
Data Management will include documentation of the systems and procedures used in data collection for 
the duration of the study. 
All CRF data collection will be performed by personnel authorized to enter, review or correct data. Data 
will be strictly confidential. 
All CRF data will be reformatted into a data structure acceptable to iRhythm. The data will be subjected 
to consistency and validation checks and will be subject to supplemental validation. 
At the conclusion of the study, completed CRF images with the date-and-time stamped audit trail 
indicating the user, the data entered, and any reason for change (if applicable) will be archived for each 
sponsor location and a backup copy archived with iRhythm. 
9.1 
Source Documentation 
Regulations and Good Clinical Practice (GCP) require that the Investigator maintain information in the 
participant’s original source documents (including medical records) that corroborates data collected on 
the case report forms. In order to comply with these regulatory requirements/GCP, the following 
information should be included in the participant record as/if applicable to the study: 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 31 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
• 
Self-reported medical history of the participant before involvement in the study sufficient to verify 
Protocol entry criteria 
• 
Dated and signed notes on the day of entry into the study referencing the Sponsor, Protocol 
number, participant ID number and a statement that informed consent was obtained 
• 
Dated and signed notes from each participant visit (for specific results of procedures and exams) 
• 
Adverse events reported and their resolution including supporting documents such as discharge 
summaries, catheterization laboratory reports, ECGs, and lab results, etc. including 
documentation of awareness of SAEs and of investigator device relationship assessment of SAEs 
at the sponsor location 
• 
Notes regarding prescription medications taken during the study for the treatment of an Adverse 
Event, the documentation will also include start and stop dates 
• 
Participant’s condition upon completion of or withdrawal from the study 
• 
Any other documents or records required to substantiate data entered into the CRF 
9.2 
Case Report Form Completion 
Primary data collection based on source-document review will be performed clearly and accurately by 
study personnel trained on the Protocol and CRF completion. The Investigator will review and sign source 
documents upon study completion for each participant, unless a clinically significant event occurs. All 
adverse events and ECG data will be assessed by medically trained Study Staff. CRF data will be collected 
for all participants in the study.  In the event the EDC System is unavailable, study personnel may 
complete paper CRFs and enter the data in the EDC System as soon as it is available.    
9.3 
Direct Access to Source Data/Documents 
The Investigator/institution will permit direct access to source data/documents in order for clinical study-
related monitoring, audits, IRB review and regulatory inspections to be performed. 
Participants providing informed consent are agreeing to allow Sponsor and/or its designee access and 
copying rights to pertinent information in their source document concerning their participation in this 
clinical study. The Investigator will obtain, as part of the informed consent, permission for clinical study 
monitors or regulatory authorities to review, in confidence, any records identifying the participants in this 
clinical study. This information may be shared with regulatory agencies; however, Sponsor undertakes 
not to otherwise release the participant's personal and private information. 
9.4 
Record Retention 
The Sponsor will archive and retain all documents pertaining to the study as per the applicable regulatory 
record retention requirements. The Investigator must obtain permission from Sponsor in writing before 
destroying or transferring control of any clinical study records. 
10.0 
ETHICAL CONSIDERATION 
10.1 
Institutional Review Board Review 
Institutional Review Board approval for the Protocol, ICF and other written information provided to the 
patient will be obtained by the Principal Investigator at each sponsor location or community clinical study 
site prior to participation in this validation study. The approval letter must be received prior to the start of 
this validation study and a copy must be provided to the Sponsor. No changes will be made to the Protocol 
or ICF or other written information provided to the patient/participant without appropriate approvals, 
including IRB, the Sponsor, and/or the regulatory agencies.  
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 32 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
Until the validation study is completed, the Investigator will advise the IRB of the progress of this study, 
per IRB requirements. Ongoing written approval will be obtained according to the IRB requirements. 
Additionally, any amendments to the Protocol as well as associated ICF changes will be submitted to the 
IRB and written approval obtained prior to implementation. 
11.0 
PUBLICATION POLICY 
The data and results from the study are the sole property of the Sponsor. The Sponsor shall have the right 
to access and use all data and results generated during this wear validation study. The Sponsor may 
publish a manuscript regarding the study results.  The recorded ECG information may be used for 
educational (including medical publications) or training purposes only, but only de-identified information 
will be used. 
The preliminary and final reports from the patch for those participants who were enrolled through the 
community clinic study site belong to the participant as part of their medical record. 
12.0 
RISK ANALYSIS 
12.1 
Anticipated Clinical Benefits 
This is a post-clearance study on the extended wear performance of the study device. Study participants 
will be asked to wear the device for as long as possible (up to 30 days) to validate performance of the 
device in up to 21 days of wear.  There are no immediate potential benefits to study participants; the 
primary long-range potential benefit is improvement in clinical standard of care for others (altruistic 
benefit to study participants).  
12.2 
Foreseeable Adverse Events and Anticipated Adverse Device Effects 
Table 3 provides a list of anticipated adverse events with wearing the study device.  If a participant 
experiences severe reaction to the device, it is recommended that the participant remove the device. 
 
Table 3: Foreseeable / Anticipated Adverse Device Effects 
Anticipated Adverse 
Device Effects (ADE) 
ADE Definition 
Allergic reaction 
Localized allergic reaction or allergic symptoms (i.e., acute urticaria) 
associated with serious injury. 
Delayed healing 
Atypical or otherwise prolonged recovery period post-wear resulting in non-
permanent injury. 
Discomfort 
Transient physical or psychological distress. 
Infection (local) 
Localized evidence of tissue invasion by pathogenic microorganisms, resulting 
in non-permanent tissue injury. 
Infection (systemic) 
Evidence of pathogenic microorganism proliferation progressed to a systemic 
disease state associated with serious injury. 
Non-functional defects 
Defects that are imperceptible to participant but identified by study staff (i.e., 
compromised aesthetics). 
Pain 
Transient physical or psychological suffering or other unpleasant feelings. 
Skin or soft tissue 
damage (permanent, 
Serious injury presenting as permanent signs of tissue structural or functional 
damage (i.e., gross scarring, localized neuropathy). 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 33 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
major) 
Skin or soft tissue 
damage (permanent, 
minor) 
Serious injury presenting as permanent changes in epidermis (i.e., abnormal 
pigmentation, blemishes). 
Skin or soft tissue 
damage (temporary, 
major) 
Signs of probable irritant contact dermatitis (edema, erythema, pruritus). 
Skin or soft tissue 
damage (temporary, 
minor) 
Minor irritation, not yet at probable irritant contact dermatitis. 
Participant annoyance 
Inconvenience perceptible to participant but unlikely to cause injury. 
Participant inconvenience 
Inconvenience imperceptible to participant but identified by study staff (i.e., 
burdensome packaging). 
 
12.3 
Risks Associated with Participation in Clinical Study 
Participation in the study requires submission of data that may or may not be protected heath 
information.  This information will be kept confidential, but there is a risk that some of the information 
could be unintentionally made non-confidential.  The risk of this happening for this study is no greater 
than the risk of loss of confidentiality in any study.   
12.4 
Possible Interactions with Protocol-Required Concomitant Medications 
There are no protocol-required medications being used as part of this study. Only medications used to 
treat adverse events will be reported.   
12.5 
Steps That Will be Taken to Control or Mitigate Risks 
Risks associated with the use of the device during this clinical study are minimized through device design, 
Investigator selection and training, pre-specified patient eligibility requirements, and study monitoring to 
ensure adherence to the protocol.   
Devices manufactured for this extended wear study will be the design cleared in K202359, with minor 
improvements in manufacturability and with the modifications necessary to allow for ECG recording up to 
30 days.  The Sponsor will have completed and documented internal Design Control requirements for all 
components of the study devices prior to first use in the extended wear study.  All adverse events and 
device deficiencies will be reported to iRhythm and will be monitored internally for safety surveillance 
purposes. 
The contraindications, warnings and precautions are listed in the IFU in the Zio monitor Clinical Reference 
Manual (Part Number DLB0035 or clinical study equivalent) that will be provided with all devices to be 
used during this study.  
12.6 
Risk to Benefit Rationale 
Foreseeable risks are outlined in Table 3.  There are no other types of foreseeable risk to participants by 
virtue of participation in this study.  Apparently healthy study participants will equally be exposed to such 
physical risks, but will be fully informed in order to assess the wear performance of the investigational 
device on a human skin.  The value of the information to be gained outweighs these procedural-related 
risks as it will support intended performance of the device. 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 34 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
Participants participating in this study will be receiving the latest technology of the currently cleared Zio 
monitor patch.  
Participants participating in the study have a small risk of loss of confidentiality as part of the data 
collection process.  This risk is mitigated to as low as possible with the use of data collection systems, 
methods and procedures that are used commonly in clinical research.  This includes the use of only 
validated electronic systems, the training of study personnel and the use of pseudo anonymized data for 
all data entry.  Based upon the established safety profile of the study device, the low risk of loss of 
confidentiality is adequately mitigated to justify use of the study device for participants in this study. 
 
 
 
 
 
This area intentionally left blank 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 35 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
 
APPENDIX I:  ABBREVIATIONS AND ACRONYMS 
 
 
 
 
 
 
 
AE 
Adverse Event 
CRF 
Case Report Form 
DD 
Device Deficiency 
DM 
Device Malfunction 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
FDA 
U.S. Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
SAE 
Serious Adverse Event 
UADE 
Unanticipated Adverse Device Effect 
USADE 
Unanticipated Serious Adverse Device Effect 
 
 
 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 36 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
APPENDIX II:  DEFINITIONS 
 
DEATH (All Cause) 
All deaths regardless of cause.  Death is further divided into 2 categories: 
1.  CARDIOVASCULAR DEATH  
Per the Valve Academic Research Consortium (VARC) [11], as any one of the following: 
• 
Any death due to proximate cardiac cause (e.g., myocardial infarction (MI), cardiac 
tamponade, worsening heart failure) 
• 
Unwitnessed death and death of unknown cause 
• 
All procedure-related deaths, including those related to a complication of the procedure 
or treatment for a complication of the procedure 
• 
Death caused by non-coronary vascular conditions such as cerebrovascular disease, 
pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular 
disease. 
2. NON-CARDIOVASCULAR DEATH 
Any death not covered by the VARC definitions of Cardiovascular Death, such as death caused by 
infection, malignancy, sepsis, pulmonary causes, accident, suicide, or trauma. 
FITZPATRICK SKIN TYPE 
The Fitzpatrick skin type is a 6-point scale [12]. 
 
Fitzpatrick 
Skin Type 
Skin 
Skin Reaction to Sun Exposure 
I 
Pale White 
Always Burns, Never Tans 
II 
Fair 
Usually Burns, Tans Minimally 
III 
Darker White 
Sometimes Mild Burn, Tans Uniformly 
IV 
Light Brown 
Burn Minimally, Always Tans Well 
V 
Brown 
Very Rarely burns, Tans Very Easily 
VI 
Dark Brown or Black 
Never Burns 
HOSPITALIZATION (ALL CAUSE) 
Defined as admission to inpatient unit or ward in the hospital for at least 24 hours, including emergency 
department stay.  Excludes hospitalizations planned for pre-existing conditions, unless there is worsening 
of a pre-existing condition.  
HYPERHYDROSIS STATE 
Hyperhidrosis status will be determined by the following definition: 
• 
Primary – Focal, visible, and excessive sweating for no apparent cause. Typically at axillae, palms, 
soles, inguinal areas, and face. 
• 
Secondary – Caused by underlying medical condition.  Can be either focal or general sweating. 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 37 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
• 
None – Only sweat during exercise, hot environment, physical, and/or psychological stress 
CHEST HAIR DENSITY 
Chest hair density will be measured by visual inspection and classified as smooth/no hair, some hair, 
moderately hairy, or very hairy in the target patch placement area. 
SKIN IRRITATION 
Severity of skin irritation will be assessed per Table 4 below.  Interpretation of the reaction will be based 
on the method recommended by the International Contact Dermatitis Research Group (ICDRG) [10,13]. 
This scale has been modified to incorporate the U.S. Food & Drug Administration (FDA) Guidance for 
Industry Skin Irritation and Sensitization Testing of Generic Transdermal Drug Products. 
Table 4: Skin Irritation Assessment 
 
Negative reaction 
(= -) 
 
 
 
Weak positive reaction 
Erythema Infiltration Discrete 
papules ( = +) 
FDA = 1 minimal erythema, barely 
perceptible 
 
Doubtful reaction 
Faint macular or homogeneous 
erythema, no infiltration (= ?) 
FDA = 0 no evidence of irritation 
 
Strong positive reaction 
Erythema Infiltration Papules 
Discrete vesicles ( = ++) 
FDA = 2-3 definite erythema, 
readily visible, papules 
 
Irritant reaction of different types 
(= IR) 
 
Extreme positive reaction 
Coalescing vesicles/bullous 
reaction (= +++) 
FDA = 4-7 definite edema, 
erythema, papules, vesicular 
eruption, spreading beyond site 
SKIN TYPE 
Skin type will be assessed at the planned patching location of the study device. 
• 
Normal 
• 
Dry – Scaling (visible peeling of outer skin layer) and skin cracking; also known as xeroderma 
• 
Oily – Excess sebum (oil) production producing shiny appearance; also known as seborrhea 
 
 
 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 38 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
VULNERABLE POPULATION (ICH E6(R3) Definition) 
Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, 
whether justified or not, of benefits associated with participation, or of a retaliatory response from senior 
members of a hierarchy in case of refusal to participate. Examples are members of a group with a 
hierarchical structure, such as medical, pharmacy, dental, and nursing students, subordinate hospital 
and laboratory personnel, employees of the pharmaceutical industry, members of the armed forces, and 
persons kept in detention. Other vulnerable participants include those with incurable diseases, persons 
in nursing homes, unemployed or impoverished persons, persons in emergency situations, ethnic minority 
groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.   
 
 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 39 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
BIBLIOGRAPHY 
1. Turakhia MP, Hoang DD, Zimetbaum P, Miller JD, Froelicher VF, Kumar UN, Xu X, Yang F, 
Heidenreich PA. Diagnostic utility of a novel leadless arrhythmia monitoring device. Am J Cardiol. 
2013;112:520–524. 
2. Survey data on file. 
3. Knight BP, et al.  Performance of a Novel Next-Generation Ambulatory ECG Long-Term Patch 
Monitor: A Multicenter Post- Market Evaluation.  Heart Rhythm 2024;21(9 Suppl):S796. 
4. Barrett PM, Komatireddy R, Haaser S, Topol S, Sheard J, Encinas J, Fought AJ, Topol EJ. 
Comparison of 24-hour Holter Monitoring with 14-day Novel Adhesive Patch Electrocardiographic 
Monitoring. The American Journal of Medicine. 2014;127:95.e11-95.e17. 
5. Rosenberg MA, Samuel M, Thosani A, Zimetbaum PJ. Use of a noninvasive continuous monitoring 
device in the management of atrial  fibrillation: a pilot study. Pacing Clin Electrophysiol. 
2013;36:328–333. 
6. Kaura A, Sztriha L, Chan FK, Aeron-Thomas J, Gall N, Piechowski-Jozwiak B, Teo JT. Early 
prolonged ambulatory cardiac monitoring in stroke (EPACS): An open-label randomised controlled 
trial. Eur J Med Res. 2019;24:25. 
7. Gupta N, Yang J, Reynolds K, Lenane J, Garcia E, Sung SH, Harrison TN, Solomon MD, Go AS. 
Diagnostic 
Yield, 
Outcomes, 
and 
Resource 
Utilization 
With 
Different 
Ambulatory 
Electrocardiographic Monitoring Strategies. Am J Cardiol. 2022;166:38-44. 
8. Reynolds MR, Passman R, Swindle J, Mohammadi I, Wright B, Boyle K, Turakhia MP, Mittal S. 
Comparative effectiveness and healthcare utilization for ambulatory cardiac monitoring 
strategies in Medicare beneficiaries. Am Heart J. 2024;269:25-34. 
9. Hannun AY, Rajpurkar P, Haghpanahi M, Tison GH, Bourn C, Turakhia MP, Ng AY. Cardiologist-
level arrhythmia detection and classification in ambulatory electrocardiograms using a deep 
neural network. Nat Med. 2019;25:65–69. 
10. Fonacier L, et. al.; American Academy of Allergy, Asthma & Immunology; American College of 
Allergy, Asthma & Immunology; Joint Council of Allergy, Asthma & Immunology. Contact dermatitis: 
a practice parameter-update 2015. J Allergy Clin Immunol Pract. 2015 May-Jun;3(3 Suppl):S1-
39. 
11. Updated standardized endpoint definitions for transcatheter aortic valve implantation: The Valve 
Academic Research Consortium-2 consensus document. Kappetein, A. Pieter et al.  The Journal 
of Thoracic and Cardiovascular Surgery, Volume 145, Issue 1, 6 – 23 
12. Fitzpatrick TB. The validity and practicality of sun-reactive skin types I through VI. Arch Dermatol. 
1988 Jun;124(6):869-71. 
13. Rietschel RL, Fowler JF Jr. Fisher's Contact Dermatitis. 5th ed. Baltimore, Md: Williams & Wilkins; 
2001.   
 
 
 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

                                          PN# TP rev. 01 
2025-03-03_SHASTA II Amd1 PROT V2_Clean 
Page 40 of 40 
 
IRHYTHM TECHNOLOGIES, INC. CONFIDENTIAL 
REVISION HISTORY 
Version # 
Released Date 
Description of Change 
02 
23 April 2025 
Updated skin prep process 
01 
15 November 2024 
Initial Release 
 
 
 
Docusign Envelope ID: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3

Certificate Of Completion
Envelope Id: EAAF9C21-1621-4B51-B6AC-44EBB134B6D3
Status: Completed
Subject: Complete with Docusign: 2025-03-03_SHASTA II Amd1 PROT V2_Clean.pdf
Source Envelope: 
Document Pages: 40
Signatures: 8
Envelope Originator: 
Certificate Pages: 6
Initials: 0
Chevy Brown
AutoNav: Enabled
EnvelopeId Stamping: Enabled
Time Zone: (UTC-08:00) Pacific Time (US & Canada)
650 Townsend St Ste 380
San Francisco, CA  94103-6248
chevy.brown@irhythmtech.com
IP Address: 4.53.130.26    
Record Tracking
Status: Original
             4/23/2025 1:54:53 PM
Holder: Chevy Brown
             chevy.brown@irhythmtech.com
Location: DocuSign
Signer Events
Signature
Timestamp
Chanda Owens
chanda.owens@irhythmtech.com
VP Quality
Security Level: Email, Account Authentication 
(None)
Signature Adoption: Pre-selected Style
Using IP Address: 68.5.133.129
Sent: 4/23/2025 1:59:41 PM
Resent: 4/29/2025 8:16:21 AM
Viewed: 4/29/2025 5:00:24 PM 
Signed: 4/29/2025 10:46:21 PM
Electronic Record and Signature Disclosure: 
      Accepted: 4/28/2025 8:26:11 AM
      ID: a59cac65-bed4-4e8f-adf9-e4fe33d503eb
Char Bame
char.bame@irhythmtech.com
Sr. Director, Clinical Research Operations
Security Level: Email, Account Authentication 
(None)
Signature Adoption: Uploaded Signature Image
Using IP Address: 12.235.16.3
Sent: 4/23/2025 1:59:41 PM
Viewed: 4/23/2025 3:16:10 PM 
Signed: 4/23/2025 3:16:21 PM
Electronic Record and Signature Disclosure: 
      Accepted: 4/23/2025 3:16:10 PM
      ID: 7d7880cc-aca1-4f56-8657-1af6bb2593a1
Chevy Brown
chevy.brown@irhythmtech.com
CR Sr. Project Manager
Security Level: Email, Account Authentication 
(None)
Signature Adoption: Pre-selected Style
Using IP Address: 4.53.130.26
Sent: 4/23/2025 1:59:43 PM
Viewed: 4/23/2025 2:00:05 PM 
Signed: 4/23/2025 2:00:13 PM
Electronic Record and Signature Disclosure: 
      Not Offered via Docusign
Christine Dunn
christine.dunn@irhythmtech.com
Sr. RA Mgr. International
Security Level: Email, Account Authentication 
(None)
Signature Adoption: Uploaded Signature Image
Using IP Address: 73.239.153.221
Sent: 4/23/2025 1:59:42 PM
Viewed: 4/24/2025 8:39:58 AM 
Signed: 4/24/2025 8:42:39 AM
Electronic Record and Signature Disclosure: 
      Accepted: 4/24/2025 8:39:58 AM
      ID: e64d590e-c210-4fe0-8167-42572985fbbe

Signer Events
Signature
Timestamp
Kevin Clarkson
kevin.clarkson@irhythmtech.com
Director, Zio XT
Security Level: Email, Account Authentication 
(None)
Signature Adoption: Pre-selected Style
Using IP Address: 12.235.16.3
Sent: 4/23/2025 1:59:45 PM
Viewed: 4/23/2025 2:02:47 PM 
Signed: 4/24/2025 3:49:56 PM
Electronic Record and Signature Disclosure: 
      Accepted: 4/23/2025 2:02:47 PM
      ID: a84a549b-9910-449a-9d4b-e8acefa203da
Mintu Turakhia
mintu.turakhia@irhythmtech.com
CMO
Security Level: Email, Account Authentication 
(None)
Signature Adoption: Pre-selected Style
Using IP Address: 98.97.26.79
Sent: 4/23/2025 1:59:43 PM
Resent: 4/29/2025 8:16:21 AM
Resent: 4/30/2025 10:21:13 AM
Viewed: 4/30/2025 10:57:55 AM 
Signed: 4/30/2025 10:58:43 AM
Electronic Record and Signature Disclosure: 
      Accepted: 4/30/2025 10:57:55 AM
      ID: 59f36d50-897f-43c7-ba5f-d0a0e440961b
TJ Battisti
tj.battisti@irhythmtech.com
Security Level: Email, Account Authentication 
(None)
Signature Adoption: Pre-selected Style
Using IP Address: 174.164.57.130
Sent: 4/23/2025 1:59:42 PM
Viewed: 4/23/2025 2:10:24 PM 
Signed: 4/23/2025 2:11:18 PM
Electronic Record and Signature Disclosure: 
      Accepted: 4/23/2025 2:10:24 PM
      ID: b8bb300d-aac4-4643-9b9f-b612aa94f4ec
Vladimir Fokin
vladimir.fokin@irhythmtech.com
Director, Data Management and Biostatistics
Security Level: Email, Account Authentication 
(None)
Signature Adoption: Pre-selected Style
Using IP Address: 172.58.124.244
Signed using mobile
Sent: 4/23/2025 1:59:44 PM
Viewed: 4/23/2025 2:00:31 PM 
Signed: 4/23/2025 2:00:56 PM
Electronic Record and Signature Disclosure: 
      Accepted: 4/23/2025 2:00:31 PM
      ID: c392d0f4-362e-47a5-836f-96541faa8ba5
In Person Signer Events
Signature
Timestamp
Editor Delivery Events
Status
Timestamp
Agent Delivery Events
Status
Timestamp
Intermediary Delivery Events
Status
Timestamp
Certified Delivery Events
Status
Timestamp
Carbon Copy Events
Status
Timestamp
Witness Events
Signature
Timestamp
Notary Events
Signature
Timestamp

Envelope Summary Events
Status
Timestamps
Envelope Sent
Hashed/Encrypted
4/23/2025 1:59:45 PM
Certified Delivered
Security Checked
4/23/2025 2:00:31 PM
Signing Complete
Security Checked
4/23/2025 2:00:56 PM
Completed
Security Checked
4/30/2025 10:58:43 AM
Payment Events
Status
Timestamps
Electronic Record and Signature Disclosure

ELECTRONIC RECORD AND SIGNATURE DISCLOSURE  
From time to time, iRhythm Technologies, Inc. (we, us or Company) may be required by law to 
provide to you certain written notices or disclosures. Described below are the terms and 
conditions for providing to you such notices and disclosures electronically through the DocuSign 
system. Please read the information below carefully and thoroughly, and if you can access this 
information electronically to your satisfaction and agree to this Electronic Record and Signature 
Disclosure (ERSD), please confirm your agreement by selecting the check-box next to ‘I agree to 
use electronic records and signatures’ before clicking ‘CONTINUE’ within the DocuSign 
system. 
 
Getting paper copies  
At any time, you may request from us a paper copy of any record provided or made available 
electronically to you by us. You will have the ability to download and print documents we send 
to you through the DocuSign system during and immediately after the signing session and, if you 
elect to create a DocuSign account, you may access the documents for a limited period of time 
(usually 30 days) after such documents are first sent to you. After such time, if you wish for us to 
send you paper copies of any such documents from our office to you, you will be charged a 
$0.00 per-page fee. You may request delivery of such paper copies from us by following the 
procedure described below. 
 
Withdrawing your consent  
If you decide to receive notices and disclosures from us electronically, you may at any time 
change your mind and tell us that thereafter you want to receive required notices and disclosures 
only in paper format. How you must inform us of your decision to receive future notices and 
disclosure in paper format and withdraw your consent to receive notices and disclosures 
electronically is described below. 
 
Consequences of changing your mind  
If you elect to receive required notices and disclosures only in paper format, it will slow the 
speed at which we can complete certain steps in transactions with you and delivering services to 
you because we will need first to send the required notices or disclosures to you in paper format, 
and then wait until we receive back from you your acknowledgment of your receipt of such 
paper notices or disclosures. Further, you will no longer be able to use the DocuSign system to 
receive required notices and consents electronically from us or to sign electronically documents 
from us. 
 
All notices and disclosures will be sent to you electronically  
Electronic Record and Signature Disclosure created on: 1/5/2021 2:43:58 PM
Parties agreed to: Chanda Owens, Char Bame, Christine Dunn, Kevin Clarkson, Mintu Turakhia, TJ Battisti, Vladimir Fokin

Unless you tell us otherwise in accordance with the procedures described herein, we will provide 
electronically to you through the DocuSign system all required notices, disclosures, 
authorizations, acknowledgements, and other documents that are required to be provided or made 
available to you during the course of our relationship with you. To reduce the chance of you 
inadvertently not receiving any notice or disclosure, we prefer to provide all of the required 
notices and disclosures to you by the same method and to the same address that you have given 
us. Thus, you can receive all the disclosures and notices electronically or in paper format through 
the paper mail delivery system. If you do not agree with this process, please let us know as 
described below. Please also see the paragraph immediately above that describes the 
consequences of your electing not to receive delivery of the notices and disclosures 
electronically from us. 
 
How to contact iRhythm Technologies, Inc.:  
You may contact us to let us know of your changes as to how we may contact you electronically, 
to request paper copies of certain information from us, and to withdraw your prior consent to 
receive notices and disclosures electronically as follows: 
To contact us by email send messages to: _hr@irhythmtech.com 
 
To advise iRhythm Technologies, Inc. of your new email address  
To let us know of a change in your email address where we should send notices and disclosures 
electronically to you, you must send an email message to us at _hr@irhythmtech.com and in the 
body of such request you must state: your previous email address, your new email address.  We 
do not require any other information from you to change your email address.  
If you created a DocuSign account, you may update it with your new email address through your 
account preferences.  
 
To request paper copies from iRhythm Technologies, Inc.  
To request delivery from us of paper copies of the notices and disclosures previously provided 
by us to you electronically, you must send us an email to _hr@irhythmtech.com and in the body 
of such request you must state your email address, full name, mailing address, and telephone 
number. We will bill you for any fees at that time, if any. 
 
To withdraw your consent with iRhythm Technologies, Inc.  
To inform us that you no longer wish to receive future notices and disclosures in electronic 
format you may: 

i. decline to sign a document from within your signing session, and on the subsequent page, 
select the check-box indicating you wish to withdraw your consent, or you may; 
ii. send us an email to _hr@irhythmtech.com and in the body of such request you must state your 
email, full name, mailing address, and telephone number. We do not need any other information 
from you to withdraw consent..  The consequences of your withdrawing consent for online 
documents will be that transactions may take a longer time to process.. 
 
Required hardware and software  
The minimum system requirements for using the DocuSign system may change over time. The 
current system requirements are found here: https://support.docusign.com/guides/signer-guide-
signing-system-requirements.  
 
Acknowledging your access and consent to receive and sign documents electronically  
To confirm to us that you can access this information electronically, which will be similar to 
other electronic notices and disclosures that we will provide to you, please confirm that you have 
read this ERSD, and (i) that you are able to print on paper or electronically save this ERSD for 
your future reference and access; or (ii) that you are able to email this ERSD to an email address 
where you will be able to print on paper or save it for your future reference and access. Further, 
if you consent to receiving notices and disclosures exclusively in electronic format as described 
herein, then select the check-box next to ‘I agree to use electronic records and signatures’ before 
clicking ‘CONTINUE’ within the DocuSign system. 
By selecting the check-box next to ‘I agree to use electronic records and signatures’, you confirm 
that: 
 
You can access and read this Electronic Record and Signature Disclosure; and 
 
You can print on paper this Electronic Record and Signature Disclosure, or save or send 
this Electronic Record and Disclosure to a location where you can print it, for future 
reference and access; and 
 
Until or unless you notify iRhythm Technologies, Inc. as described above, you consent to 
receive exclusively through electronic means all notices, disclosures, authorizations, 
acknowledgements, and other documents that are required to be provided or made 
available to you by iRhythm Technologies, Inc. during the course of your relationship 
with iRhythm Technologies, Inc..