Clinical Evaluation of the CM-1500 in Postoperative Abdominal and Pelvic Surgery Patients
Phase: NA
Conditions: Blood Loss
Sponsor: Zynex Monitoring Solutions

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 1 of 33 
 
CLINICAL PROTOCOL 
ZMS-1500-2001 
NCT#04706221 
13-MAY-2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 2 of 33 
 
CLINICAL PROTOCOL 
 
 
TITLE 
 
Clinical Evaluation of the CM-1500 in Postoperative Abdominal and 
Pelvic Surgery Patients 
 
PROTOCOL NO. 
ZMS-1500-2001 
 
SPONSOR 
Zynex Monitoring Solutions (ZMS) 
9555 Maroon Circle 
Englewood, CO 80112 
 
IRB/ETHICS COMMITTEE  
Wake Forest University Health Sciences 
Office of Research Institutional Review Board 
Medical Center Boulevard 
Winston-Salem, NC 27157-1023 
 
 
 
PROTOCOL VERSION 
01/03/2021 
 
 
IDE: 
 
NA 
DOCUMENT REVIEW  
& APPROVAL 
 
 
 
 
 
Investigator(s): 
 
 
 
Ashish Khanna, MD 
 
 
 
 
 
 
 
Sponsor Representative(s): 
 
 
 
 
 
Signature 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
Signature 
 
Date 
 
 
 
CONFIDENTIALITY STATEMENT 
This document is the confidential information of Zynex. It is provided to you as an investigator or 
consultant for review by you, your personnel, and the applicable Institutional Review Board/Ethics 
Committee. Your acceptance of this document constitutes an agreement that you cannot disclose the 
information contained herein to others without the prior written consent of Zynex. 
 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 3 of 33 
 
 
PROTOCOL SIGNATURE PAGE 
 
TITLE 
Clinical Evaluation of the CM-1500 in Postoperative Abdominal and 
Pelvic Surgery Patients 
PROTOCOL NO. 
ZMS-1500-2001 
SPONSOR 
Zynex Monitoring Solutions (ZMS) 
9555 Maroon Circle 
Englewood, CO 80112 
IRB APPROVAL DATE 
 
12-JAN-2021 
PROTOCOL VERSION 
1.1 
 
 
The signature below constitutes I have read, understood, and approve this protocol and provide 
assurances that this trial will be conducted according to all stipulations of the protocol, including all 
statements regarding subject confidentiality, and according to local legal and regulatory requirements, 
including all applicable U.S. federal and local regulations and ICH guidelines. 
 
I agree to supervise all testing of the device involving human subjects. I confirm I will ensure Informed 
Consent requirements will be met for all subjects. I confirm I will ensure Informed Consent of each 
subject is obtained before any study procedures; protect the rights, safety, and welfare of all study 
subjects; prepare and maintain accurate, current, and complete records (including Adverse Events); 
provide timely reports to the IRB; ensure changes are not implemented without prospective IRB 
approval unless required to eliminate an immediate hazard to subjects; retain records as set out in the 
protocol; disclose relevant financial information. 
 
 
 
 
Principal Investigator (PI): 
Ashish Khanna, MD 
 
 
PI Printed Name 
 
 
 
 
 
 
 
PI Signature 
 
 
 
 
 
 
 
Date (DD-MMM-YYYY) 
 
 
 
CONFIDENTIALITY STATEMENT 
This document is the confidential information of Zynex. It is provided to you as an investigator or 
consultant for review by you, your personnel, and the applicable Institutional Review Board/Ethics 
Committee. Your acceptance of this document constitutes an agreement that you cannot disclose the 
information contained herein to others without the prior written consent of Zynex. 
 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 4 of 33 
 
 
PROTOCOL AMENDMENT HISTORY 
 
Version 
Number 
IRB Approval Date 
Description of Change(s) 
1.0 
12-JAN-2021 
Initial protocol; no changes 
1.1 
13-MAY-2021 
Increased the number of subjects from 100 to 200 and removed 
laparoscopic so that both open and laparoscopic procedures are 
allowed to be enrolled. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[This space is intentionally left blank] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CONFIDENTIALITY STATEMENT 
This document is the confidential information of Zynex. It is provided to you as an investigator or 
consultant for review by you, your personnel, and the applicable Institutional Review Board/Ethics 
Committee. Your acceptance of this document constitutes an agreement that you cannot disclose the 
information contained herein to others without the prior written consent of Zynex. 
 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 5 of 33 
 
 
 
 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 6 of 33 
 
Table of Contents 
1 
ABBREVIATIONS AND DEFINITIONS OF TERMS .................................................................. 10 
Table 1: Abbreviations and Definition of Terms .............................................................................. 10 
2 
INTRODUCTION .............................................................................................................................. 11 
3 
INVESTIGATIONAL PLAN ............................................................................................................ 11 
3.1 
OBJECTIVE .............................................................................................................................. 11 
3.2 
STUDY DURATION ................................................................................................................. 11 
3.3 
STUDY DESIGN ....................................................................................................................... 11 
4 
CM-1500 (“DEVICE”) ..................................................................................................................... 11 
4.1 
DEVICE DESCRIPTION ......................................................................................................... 11 
4.1.1 
DEVICE DESIGN AND COMPONENTS ...................................................................... 12 
4.2 
PRINCIPLES OF OPERATION .............................................................................................. 12 
4.3 
INDICATIONS FOR USE ........................................................................................................ 12 
4.4 
INTENDED USE ....................................................................................................................... 12 
5 
SUBJECT POPULATION AND SELECTION ............................................................................. 13 
5.1 
POPULATION AND ANTICIPATED NUMBER OF SUBJECTS ....................................... 13 
5.2 
SUBJECT INCLUSION CRITERIA ........................................................................................ 13 
5.3 
SUBJECT EXCLUSION CRITERIA ...................................................................................... 13 
5.4 
SUBJECT SCREEN FAIL CRITERIA ................................................................................... 13 
5.5 
SUBJECT WITHDRAW / EARLY TERMINATION CRITERIA .......................................... 13 
5.6 
CONCOMITANT MEDICATIONS/ CONCURRENT MEDICATIONS ............................... 14 
5.6.1 
PROHIBITED MEDICATIONS ....................................................................................... 14 
6 
STUDY GROUPS & ASSIGNMENT ............................................................................................. 14 
7 
STUDY PROCEDURES .................................................................................................................. 14 
7.1 
ENROLLMENT ......................................................................................................................... 14 
7.1.1 
INFORMED CONSENT/ RESEARCH INFORMATION SHEET ............................... 14 
7.2 
SCREENING ............................................................................................................................. 14 
7.2.1 
DEMOGRAPHICS ............................................................................................................ 15 
7.2.2 
MEDICAL & SURGICAL HISTORY ............................................................................... 15 
7.2.3 
CONCOMITANT MEDICATIONS .................................................................................. 15 
7.3 
VISIT 1 ....................................................................................................................................... 15 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 7 of 33 
 
7.3.1 
PREPARING DEVICE FOR USE .................................................................................. 15 
7.3.2 
PREPARING THE SUBJECT FOR DEVICE USE ...................................................... 16 
7.3.3 
DEVICE USE/OPERATION ............................................................................................ 17 
7.3.4 
OBSERVATION ................................................................................................................ 18 
7.4 
UNANTICIPATED DEVICE EFFECT (UADE) ..................................................................... 18 
7.5 
FOLLOW-UP VISIT/CONTACT ............................................................................................. 18 
7.6 
SUBJECT COMPLETION ....................................................................................................... 18 
7.7 
SCHEDULE OF EVENTS TABLE ......................................................................................... 19 
Table 2: Schedule of Events ............................................................................................................... 19 
8 
STUDY SUPPLIES AND EQUIPMENT ........................................................................................ 19 
8.1 
STUDY SUPPLIES .................................................................................................................. 19 
8.2 
DEVICE EQUIPMENT ............................................................................................................. 19 
8.3 
SAFETY EQUIPMENT ............................................................................................................ 19 
9 
DEVICE MANAGEMENT................................................................................................................ 19 
9.1 
UNPACKING AND INSPECTION .......................................................................................... 19 
9.2 
ACCOUNTABILITY .................................................................................................................. 19 
9.3 
STORAGE ................................................................................................................................. 20 
9.4 
DISPENSATION ....................................................................................................................... 20 
9.5 
LABELING ................................................................................................................................. 20 
9.6 
CLEANING ................................................................................................................................ 20 
9.7 
RETURN .................................................................................................................................... 20 
10 
RISKS & BENEFITS ................................................................................................................... 20 
10.1 
RISK DETERMINATION ......................................................................................................... 20 
10.2 
RISKS......................................................................................................................................... 20 
10.2.1 
RISKS: USING THE DEVICE ......................................................................................... 21 
10.2.2 
WARNINGS: CM-1500 DEVICE .................................................................................... 21 
10.2.3 
CAUTIONS: CM-1500 DEVICE ..................................................................................... 21 
10.2.4 
CONTRADICTIONS: CM-1500 DEVICE ...................................................................... 22 
10.3 
REDUCING RISKS TO A MINIMUM ..................................................................................... 22 
10.4 
BENEFITS ................................................................................................................................. 23 
11 
SAFETY ASSESSMENT AND MANAGEMENT .................................................................... 23 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 8 of 33 
 
11.1 
SAFETY PARAMETERS ........................................................................................................ 23 
11.2 
MEDICAL DEVICE REPORTING .......................................................................................... 23 
11.3 
SAFETY DEFINITIONS ........................................................................................................... 23 
11.3.1 
ADVERSE EVENT (AE) .................................................................................................. 23 
Table 3: Adverse Event Severity Grading .................................................................................... 23 
Table 4: Adverse Events Action(s) Taken .................................................................................... 23 
Table 5: Adverse Event Relationship to Investigation ................................................................ 23 
Table 6: Adverse Event Outcome .................................................................................................. 23 
11.3.2 
SERIOUS ADVERSE EVENT (SAE) ............................................................................ 24 
11.3.3 
UNANTICIPATED ADVERSE DEVICE EFFECT (UADE) ......................................... 24 
Table 7: Unanticipated Adverse Device Effect Subject Outcome ............................................. 24 
Table 8: Unanticipated Adverse Device Effect ............................................................................ 25 
11.4 
RECORDS ................................................................................................................................. 25 
11.5 
SAFETY REPORTING ............................................................................................................ 25 
11.5.1 
REPORTING EVENTS & SAFETY CONTACTS ........................................................ 26 
Table 9. Safety Reporting Contacts .............................................................................................. 26 
12 
STATISTICAL METHODS AND CONSIDERATIONS ........................................................... 26 
12.1 
SAMPLE SIZE DETERMINATION ........................................................................................ 26 
12.2 
DATA SETS ANALYZED ........................................................................................................ 26 
12.3 
DEMOGRAPHIC AND BASELINE CHARACTERISTICS ................................................. 26 
12.4 
STATISTICAL ANALYSIS PLAN (SAP) ............................................................................... 26 
13 
DATA COLLECTION, RETENTION, AND MONITORING ................................................... 28 
13.1 
DATA COLLECTION ............................................................................................................... 28 
13.1.1 
SUBJECT CONFIDENTIALITY ...................................................................................... 28 
13.2 
DATA RETENTION .................................................................................................................. 28 
13.3 
MONITORING ........................................................................................................................... 28 
13.3.1 
MONITORING PLAN ....................................................................................................... 28 
14 
STUDY ADMINISTRATION ....................................................................................................... 29 
14.1 
AUDITS AND INSPECTIONS ................................................................................................ 29 
14.2 
PROTOCOL .............................................................................................................................. 29 
14.2.1 
STRUCTURE .................................................................................................................... 29 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 9 of 33 
 
14.2.2 
PROTOCOL AMENDMENTS ......................................................................................... 29 
14.2.3 
PROTOCOL DEVIATIONS ............................................................................................. 29 
14.3 
INFORMED CONSENT FORM (ICF) AMENDMENTS ...................................................... 29 
15 
ETHICAL AND OTHER REGULATORY CONSIDERATIONS ............................................ 29 
15.1 
INSTITUTIONAL REVIEW BOARD (IRB) / ETHICS COMMITTEE (EC) REVIEW ....... 30 
15.2 
INFORMED CONSENT WITH WAIVER OF DOCUMENTATION .................................... 30 
16 
REFERENCES ............................................................................................................................. 30 
Appendix A. Device Unpacking and Inspection Form ................................................................. 32 
Appendix B. Device Accountability Log .......................................................................................... 33 
 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 10 of 33 
 
1 
ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
Table 1: Abbreviations and Definition of Terms 
 
Abbreviation 
Definition 
AE 
Adverse event 
BPM 
Beats per minute 
C 
Celsius 
CFR 
U.S. Code of Federal Regulations 
CM-1500 
Cardiac Monitor, Model 1500 
CRF 
Case report form 
EC 
Ethics Committee 
ECG / EKG 
Electrocardiogram 
e.g. 
Exempli Gratia (for example) 
eCRF 
Electronic Case Report Form 
FDA  
U.S. Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
HR 
Heart rate 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
ISF 
Investigator Site File 
ISO 
International Organization for Standardization 
lb. 
Pound; unit of mass 
ohms 
Unit of electrical resistance, plural 
OTC 
Over-the-counter 
mL 
Milliliter 
MRI 
Magnetic Resonance Imaging 
PACU 
Post-anesthesia Care Unit 
PHI 
Protected Health Information 
PI 
Principal Investigator 
PPG 
Photoplethysmogram  
SAE 
Serious adverse event 
SOP 
Standard Operating Procedure 
Sub-I 
Sub-Investigator 
UADE 
Unanticipated Adverse Device Event 
ZMS 
Zynex Monitoring Solutions 
 
 
 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 11 of 33 
 
2 
INTRODUCTION 
Postoperative hemorrhage incidence can vary depending on the type of surgery, but it 
can lead to severe clinical complications ranging from mild anemia to fatal hemorrhagic 
shock. One study conducted by Mañas-Gómez et al. (2011) evaluated 107 post-
pancreaticoduodenectomy (PD) patients between January 2005 and December 2008 and 
found that 16.82% (18/107) patients hemorrhaged after PD. Of those, four (4) of the 
eighteen (18) patients hemorrhaged early (< 24 hours).1 The study also found that 
hemorrhage after pancreatic resection may be considered a complication with a high 
mortality rate. Ansari et al. (2016) conducted a retrospective observational study on 500 
consecutive patients undergoing major pancreatic resections.2 The study found that 
13.6% (68 patients) developed post-pancreatectomy hemorrhage.2  
Monitoring and detecting these fluid changes postoperatively can be complicated, and 
standard operating procedures vary.  The Cardiac Monitor, Model 1500 (CM-1500), uses 
a personalized approach by non-invasively and simultaneously monitoring five (5) 
physiological parameters, including bioelectrical impedance, ECG Amplitude, PPG 
Amplitude, heart rate, and skin temperature. The CM-1500 starts by creating a baseline 
for each patient in a relaxed state. When the monitoring session starts, each patient starts 
with a Relative Index of 100 signifying parameters near their original baseline value. The 
Relative Index value acts as a combinational score of percent change values for all the 
parameters indicative of relative fluid change as parameters change towards indications 
of fluid change or imbalance.  
3 
INVESTIGATIONAL PLAN 
3.1 OBJECTIVE 
The primary objective is to evaluate the changes in the Relative Index in post abdominal 
or pelvic surgery patients (both laparoscopic and open procedures). 
3.2 STUDY DURATION 
Enrollment is expected to take up to 12 months. Data analysis is expected to take up to 
6 months after enrollment is completed. 
3.3 STUDY DESIGN 
The study is a prospective, single-arm, non-randomized, non-controlled, single-center 
study enrolling adult subjects. 
4 
CM-1500 (“DEVICE”) 
4.1 DEVICE DESCRIPTION 
The CM-1500 is a U.S. Food and Drug Administration (FDA) cleared non-invasive 
monitoring device that simultaneously monitors five (5) parameters of a patient’s body. 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 12 of 33 
 
Parameters include bioelectrical impedance, heart rate, ECG amplitude, PPG amplitude, 
and skin temperature. A combination of these parameters is represented by a single 
number known as the Relative Index value. This value is indicative of relative changes in 
fluid volume. The Relative Index is a unique functionality of the Zynex CM-1500. 
4.1.1 DEVICE DESIGN AND COMPONENTS 
The CM-1500 is an all-inclusive device that includes the following components: display 
monitor (1), power supply (1), trunk cable (1), wrist cuff with attached PPG finger glove 
(1), wrist strap (1), and electrode array set (2). The wrist cuff with attached PPG finger 
glove may be cleaned and reused. The wrist strap is single-subject use. The electrode 
array sets are single-use, single-subject. 
4.2 PRINCIPLES OF OPERATION 
The CM-1500 measures bioelectrical impedance (ohms), heart rate (BPM), ECG 
amplitude, PPG amplitude, and skin temperature (◦C). As parameters change, towards 
indications of fluid change/imbalance, the Relative Index, which acts as a combinational 
score of percent change values for all of the parameters, will compound these changes 
into a singular value to signify overall fluid changes/imbalances within the patient’s body. 
When the monitoring session starts, every patient will start with a Relative Index of 100, 
signifying the combination of physiological parameters is near or at their original baseline 
values for all five monitored parameters. All parameters are continuously measured and 
tracked during a monitoring session. ECG and PPG amplitude values are only visible on 
the Advanced monitoring session display mode, as selected in the Setup screen. 
4.3 INDICATIONS FOR USE 
Per the device’s FDA clearance, the indications for use including monitoring of the 
following parameters and their relative changes, indicative of relative changes in fluid 
volume in adult patients: bioelectrical impedance, heart rate, ECG amplitude, and PPG 
amplitude. 
4.4 INTENDED USE 
Per the device’s FDA clearance, the CM-1500 is intended to be used in professional 
medical environments, i.e., hospitals, clinics, and research institutions. The CM-1500 is a 
standalone device intended for desktop use, where device operation is to be performed 
as uninterrupted patient monitoring. The CM-1500 shall only be used by a qualified device 
operator. The operator shall have knowledge of the system and data interpretation 
obtained via medical education, system documentation, and specific courses. The device 
does not report any diagnosis but provides numerical values; it is ultimately the 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 13 of 33 
 
physician’s responsibility to make proper diagnosis and judgments based on these 
values. 
5 
SUBJECT POPULATION AND SELECTION 
5.1 POPULATION AND ANTICIPATED NUMBER OF SUBJECTS 
We anticipate up to 200 adult subjects who meet the inclusion and exclusion criteria to 
enroll in the study.  
5.2 SUBJECT INCLUSION CRITERIA 
I.1 
Ability to provide written informed consent 
I.2 
Ability and willingness to comply with study procedures and duration requirements 
I.3 
18 years of age or older 
I.4 
Undergoing an abdominal or pelvic surgery within the next 10 days, be it 
laparoscopic or open procedure 
5.3 SUBJECT EXCLUSION CRITERIA 
E.1 
Females who are pregnant or breastfeeding 
E.2 
Participation in other clinical studies involving experimental drugs or devices 
E.3 
Undergone an amputation of the left upper extremity 
E.4 
Diagnosed with Dextrocardia 
E.5 
Subjects who have a Pacemaker 
5.4 SUBJECT SCREEN FAIL CRITERIA 
Subjects who are determined to be a Screen Fail may be replaced.  
SF.1 After Enrollment, the subject is found not to meet the inclusion/exclusion criteria. 
Enrollment is defined as the subject has provided verbal Informed Consent. 
5.5 SUBJECT WITHDRAW / EARLY TERMINATION CRITERIA 
Subjects who are withdrawn from the study before using the device may be replaced. 
Subject withdrawal/early termination criteria are listed below.  
W.1 
The subject requests to be withdrawn from the study or withdraws consent. 
W.2 
The subject refuses to comply with the required study procedures. 
W.3 
An Adverse Event (AE) (related to the investigation or not) makes the continuation 
of the subject impossible or inadvisable. 
W.4 
The Investigator determines it is in the subject’s best interest to discontinue from 
the study. 
W.5 
The Sponsor terminates the Investigator, Site, or the Study. 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 14 of 33 
 
5.6 CONCOMITANT MEDICATIONS/ CONCURRENT MEDICATIONS 
All concomitant medications will be recorded from screening through study completion. 
5.6.1 PROHIBITED MEDICATIONS 
Prohibited medications include any experimental drugs while participating in the study 
(E.2). 
6 
STUDY GROUPS & ASSIGNMENT 
This study is a prospective, non-randomized, non-controlled study. Each subject will 
undergo the same procedures. 
 
7 
STUDY PROCEDURES 
 
7.1 ENROLLMENT 
A subject has enrolled in the study after the subject has provided written informed 
consent. 
7.1.1 INFORMED CONSENT/ RESEARCH INFORMATION SHEET 
All potentially eligible subjects will undergo formal screening by members of the 
research teams at each site and confirmed by the site Investigator to be a candidate for 
the study. The PI or his designee will review and explain the contents of the informed 
consent document to the eligible subject.  The potential subject or family member will be 
informed of the purpose of the study, the randomization procedure, and the risks and 
benefits of participation. The potential subject will also be informed that he/she may 
refuse to participate, and that even if he/she consents to participate he/she may 
withdraw from the study at any time.  
If the subject does not consent to participate, he/she will not be admitted to the study.   
 
7.1.2 SCREENING 
Screening procedures are estimated to take approximately 1 hour. Screening procedures 
include obtaining demographics, medical and surgical history, and concomitant 
SCREENING (Day 1)
•ICF (waiver of 
Documentation)
•Inclusion/Exclusion
•Demographics
•Medical & Surgical 
History 
•ConMeds
VISIT 1 (Day 1)
•Preparing the Device
•Preparing the Subject
•Device 
Operation/Monitoring 
Session
•Observation
FOLLOW UP 
(7+/- 5 days)
•Follow up is only 
required for subjects 
who have a poor 
outcome.

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 15 of 33 
 
medications. This information is gathered via chart review and may be self-reported by 
the subject.  
7.1.3 DEMOGRAPHICS 
Demographic information, including the subject’s year of birth or age, sex, gender, race, 
and ethnicity, will be recorded at Screening.  
7.1.4 MEDICAL & SURGICAL HISTORY 
Relevant medical and surgical history will be recorded at the Screening. This includes 
any medical condition(s) diagnosed or surgeries that occurred before Screening through 
study completion. The height (inches), weight (pounds), and the type of surgery the 
subject is undergoing will also be recorded.  
7.1.5 CONCOMITANT MEDICATIONS 
Concomitant Medications (conmeds) are defined as prescription, over-the-counter OTC 
drugs, or dietary supplements a subject takes while participating in the study and 2 weeks 
prior. All concomitant medications will be recorded at Screening through study 
completion. 
7.2 VISIT 1 
Visit 1 is estimated to take approximately 2-6 hours. Visit 1 includes preparing the device 
for use, preparing the subject for device use, operating the device (monitoring session), 
and observation. Visit 1 will occur on the same day as Screening. 
7.2.1 PREPARING DEVICE FOR USE 
The Investigator or qualified designated study personnel will prepare the device for use 
by referencing the Instructions for Use (IFU) manual and following the study-specific steps 
outlined below. 
S1. 
Complete the Unpacking, Inspection, and Accountability procedures and 
associated forms (refer to IFU for the full procedure). 
S2. 
Ensure the device is in a secure and stable location (refer to IFU for the full 
procedure). 
S3. 
To supply power to the CM-1500, connect the power supply cord to the display 
monitor and an electrical outlet. The light will illuminate on the power adapter when 
it is connected to power.  
S4. 
To connect the display monitor to the wrist cuff, connect the CM-1500 wrist cuff 
trunk cable to the display monitor. The cable should double-click into the correct 
insertion position. 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 16 of 33 
 
S5. 
Connect the CM-1500 wrist cuff to the trunk cable. The cable should double-click 
into the correct insertion position. 
S6. 
Power on the device by pressing the external “ON/OFF” button located on the right 
side of the display monitor. 
S7. 
Press the “SETUP” button and select the desired user preferences, patient 
information, device storage mode, and device information. Press “SAVE” after all 
desired setup options are selected. 
a. 
On the “SETUP” screen, complete user preferences, subject information 
(sex and subject number), data storage mode, and review device 
information. By pressing “SAVE,” the device will return to the Monitoring 
Screen. 
S8. 
Insert a USB external storage drive (refer to “Data Storage Mode” in the IFU). The 
USB external storage drive should be labeled externally with the subject number. 
The USB should display a solid red light. 
7.2.2 PREPARING THE SUBJECT FOR DEVICE USE 
After the device is prepared for use, the Investigator or qualified designated study 
personnel will prepare the subject for device use by referencing the Instructions for Use 
(IFU) manual and following the study-specific steps outlined below. The subject’s position 
(supine, prone, fowlers, R/L lateral recumbent) throughout the study may be recorded. 
The subject will be prepared for device use within 15 minutes  (but no longer than 1 hour) 
after the subject’s surgery. Monitoring/device use will occur in the recovery room and 
PACU. 
S9. 
Clean the subject’s skin on his or her left wrist. 
S10. Take the small white connector/electrode array and remove the transparent plastic 
film attached to the electrodes to expose the adhesive. Place the small white 
connector/electrode array on the dorsal (top) of the subject’s left wrist. The white 
connector shall be pointed medially (inward) towards the subject’s body. 
S11. Take the large blue connector/electrode array and remove the transparent plastic 
film attached to the electrode to expose the adhesive. Place the large blue 
connector/electrode array on the left side of the neck’s base and down across the 
front of the shoulder (above the clavicle). The blue connector shall point away from 
the neck, extending toward the direction of the left shoulder. 
S12. Place the wrist cuff on the subject’s left wrist (above or over the top of the white 
electrode array), with the trunk cable connection point up the arm, and secure the 
wrist strap around the left wrist. The cuff should be snug with no gap between the 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 17 of 33 
 
wrist cuff and skin. The wrist cuff should not slide or rotate without being too tight 
or restricting blood flow. 
S13. Place the PPG finger glove on the subject’s left digitus II manus (Index) fingertip. 
The white cable/top side of the finger glove should be on the dorsal (top) side of 
the finger. The fingertip shall be touching the end of the inside of the glove. 
Fingernails will often protrude from the end of the finger glove, which is normal.  
S14. Examine the trunk cable to ensure that it is connected securely to the CM-1500 
display monitor and the wrist cuff. 
S15. Connect both CM-1500 electrode array sets to the corresponding electrode lead 
cables protruding from the wrist cuff. The blue connector/electrode array set shall 
connect to the blue lead cable connector on the wrist cuff. The white 
connector/electrode array shall connect to the white lead cable connector on the 
wrist cuff. The lead cable connectors are shaped to match the electrode 
connectors. 
NOTE: Ensure connectors are properly aligned before inserting (DO NOT 
FORCE THE CONNECTION).  
7.2.3 DEVICE USE/OPERATION 
The Investigator or qualified designated study personnel will operate the device by 
referencing the Instructions for Use (IFU) manual and following the study-specific steps 
outlined below. Device operation will begin within 15 minutes (but no longer than 1 hour) 
after the subject’s surgery. Sites will not use the device for clinical decisions but instead 
follow their standard operating procedures for monitoring postoperative subjects.  
S16. Start the monitoring session by pressing “START” on the CM-1500 display 
monitor/monitoring screen. A message will appear informing the user that the 
monitoring session is in progress. The device will begin to measure all five (5) 
parameters. 
S17. As monitoring continues, the display will show ECG and PPG pulse waveforms 
along with the Relative Index graph over time. Baseline measurements for all 
parameters are taken at the beginning of the monitoring session and are critical to 
the performance of the Relative Index. The subject should be relaxed during 
baseline establishment. The subject should remain in a supine position (with an 
allowance to be 30 degrees head up) if possible.  
S18. Continue the monitoring session for at least 60 minutes  but no longer than 6 hours 
postoperatively. The device will monitor until “STOP” is pressed on the monitoring 
screen. Document any observations or adverse events that occur during the 
monitoring session. 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 18 of 33 
 
S19. After the monitoring session is stopped, remove the electrode array sets from the 
subject and dispose of the electrodes per site guidelines. 
7.2.4 OBSERVATION 
The site will follow its standard operating procedure (SOP) to monitor postoperative 
subjects in the recovery room and PACU. The Investigator or qualified designated study 
personnel will continue monitoring the subject and observe the subject for at least 1 hour 
but no longer than 6 hours postoperatively. Any observations can be recorded (by using 
the mark event button on the CM-1500 device), but it is not required as all relevant events 
will be recorded in the patients medical records as per the SOP of the site. Observations 
may include but are not limited to indoor temperature of the postoperative recovery room 
or PACU, time and type of medication delivery, vital sign data (as obtained as part of the 
sites SOP), and the subject’s position. Following/using the site’s SOP, should the subject 
show signs of hemorrhage or a potentially poor outcome,the site will note this in the EMRs 
including time and date of the observation.  
After the observation period is complete, the monitoring session will be stopped, and the 
electrode array sets will be removed and disposed of. Redacted medical records will be 
provided to the Sponsor.  
7.3 UNANTICIPATED DEVICE EFFECT (UADE) 
Unanticipated Adverse Device Effect (UADE) that occurs after informed consent and 
before completion of the study will be recorded. UADE’s may require follow-up contact 
via study visit, telephone call, or both depending on the nature of the UADE. 
7.4 FOLLOW-UP VISIT/CONTACT 
In the event of a poor outcome due to the subject’s surgery, the Investigator or qualified 
designated study personnel will perform follow-up contact via telephone call 7(±5) days 
after the outcome occurred. The Investigator or study personal will record any follow-up 
attempts or contact made. Should the outcome not be resolved in 7(±5) days, follow up 
might continue until resolved, or the outcome will be notated as unknown upon approval 
by the Sponsor.  
7.5 SUBJECT COMPLETION 
A subject has completed the study when all Screening, Visit 1, and, when applicable, 
follow-up contact is completed and documented. 
 
 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 19 of 33 
 
7.6 SCHEDULE OF EVENTS TABLE 
Table 2: Schedule of Events 
STUDY PROCEDURE 
SCREENING 
Day 1 
VISIT 1 
Day 1 
FOLLOW UP CONTACT 
Day 7 (± 5) 
Informed Consent  
(waiver of documentation) 
X 
 
 
Inclusion/Exclusion 
X 
 
 
Demographics  
X 
 
 
Medical and Surgical History 
X 
 
 
Concomitant Medications 
X 
 
(X) if applicable 
Prepare Device for Use 
 
X 
 
Prepare Subject for Device Use 
 
X 
 
Device Operation/Monitoring Session 
 
X 
 
Observation 
 
X 
 
Adverse Events Review 
 
X 
(X) if applicable 
Follow-Up Contact 
 
 
(X) if applicable 
 
8 
STUDY SUPPLIES AND EQUIPMENT 
8.1 STUDY SUPPLIES 
Study-specific supplies will include alcohol wipes for CM-1500 electrode application(s). 
8.2 DEVICE EQUIPMENT 
CM-1500, including the display monitor and all component accessories. 
8.3 SAFETY EQUIPMENT 
No additional study-specific safety equipment will be required for the investigation. The 
site will follow their postoperative standard operating procedures.  
9 
DEVICE MANAGEMENT 
9.1 UNPACKING AND INSPECTION 
It is the responsibility of the Principal Investigator (PI) to ensure that all devices are 
unpacked and inspected prior to using in any study procedures. Upon arrival, the 
Investigator will remove the device display monitor and accessories from the shipping 
container; ensure all device components are received; complete the unpacking and 
inspection checklist in Appendix A. The study site must inform the Sponsor of any missing 
or damaged items within seven (7) days.  Devices with any missing or damaged items 
cannot be used and shall be replaced. 
9.2 ACCOUNTABILITY 
It is the responsibility of the Principal Investigator to ensure all devices are inventoried 
and accounted for. The Investigator or qualified designated study personnel will record 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 20 of 33 
 
all information on the Device Accountability logs (Appendix B) and maintain a copy in the 
Investigator Site Files (ISF). 
9.3 STORAGE 
The device(s) will be stored at the study center. When not in use, the device(s) will be 
stored in a secure location (i.e., area with limited access or in a locked cabinet) under 
appropriate environmental conditions found in the Instructions for Use (IFU) manual. 
9.4 DISPENSATION 
The device shall only be used under the supervision of the Principal Investigator. Study 
Personnel shall not use the device on any person not authorized to receive it. 
9.5 LABELING 
Investigational device(s) will be labeled with the name and place of business of the 
manufacturer, quantity of contents if applicable, and the statement “CAUTION- 
Investigational Device. Limited by Federal (U.S.) Law to Investigational Use.” In the 
instance that a production (commercial) device is used, investigational labels will not be 
applicable, and instead, production labeling will be used. 
9.6 CLEANING 
The device shall be cleaned before each use. Cleaning procedures will be followed per 
the Instructions for Use (IFU) manual. The device should always be turned off and 
disconnected before cleaning. The site will follow site-specific COVID19-related cleaning 
policies as applicable. 
9.7 RETURN 
The device(s) shall be returned to the Sponsor after study completion.  
10 RISKS & BENEFITS 
10.1 RISK DETERMINATION 
This investigation is a Piovotal study that is determined to be an non-exempt, non-
significant risk investigation. An Investigational Device Exemption (IDE) will be 
submitted based on this determination. The device will be used as intended  and no 
clinical decisions will be made based off of the information obtained.  
10.2 RISKS 
The CM-1500 is a Class II, non-invasive, non-significant risk medical device and does not 
meet the definition of significant risk under 21 CFR 812.3(m). Adverse events related to 
the investigation will be recorded and analyzed to evaluate their significance. A report will 
be written on the findings. There may be other risks that are unknown. 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 21 of 33 
 
10.2.1 RISKS: USING THE DEVICE 
- 
[Possible, Rare] Skin irritation could occur from the electrodes  
10.2.2 WARNINGS: CM-1500 DEVICE 
- 
When using the external power supply, this electrical device does not incorporate 
a power switch to isolate the system from the ac mains. Unplug the power cord of 
the ac adapter from the ac mains outlet in order to completely disconnect from the 
main ac power. Ensure that the AC outlet used for the CM-1500 is easily 
accessible. 
- 
BURN HAZARD: Simultaneous connection of a patient to high-frequency surgical 
equipment or electrocautery may result in burns at the site of the electrodes and 
possible damage to the CM-1500. 
- 
BURN HAZARD: Do not use the CM-1500 or sensors during magnetic resonance 
(MR) scanning. The induced current could potentially cause burns. The CM-1500 
may affect the MR device, and the MR device may affect the accuracy of the CM-
1500 parameters and measurements. 
- 
BURN HAZARD: Do not use the CM-1500 or sensors during defibrillation. 
- 
EXPLOSION HAZARD: Do not use the CM-1500 in the presence of flammable 
anesthetics or other flammable substances in combination with air, oxygen-
enriched environments, or nitrous oxide. 
- 
ELECTRIC-SHOCK HAZARD: Do not open the CM-1500 cover. Only a qualified 
operator may perform maintenance procedures specifically described in the IFU 
manual. Refer to Zynex for the repair of this equipment. 
- 
ELECTRIC-SHOCK HAZARD: Do not open the power adapter. Refer to Zynex for 
the repair or replacement of this equipment. ONLY USE AN APPROVED POWER 
SUPPLY THAT SATISFIES THE Power Supply Specifications! 
- 
To protect against injury from electric shock, follow these guidelines: 
• Avoid placing the device on surfaces with visible liquid spills. 
• Do not soak or immerse the device in liquids. 
• 
Use cleanings solution sparingly and only externally on the device 
10.2.3 CAUTIONS: CM-1500 DEVICE 
- 
Tissue damage can be caused by an incorrect application or use of a sensor (e.g., 
fastening the wrist cuff too tightly). Inspect the sensor sites as directed to ensure 
skin integrity, correct positioning, and adequate adhesion of the sensors and 
electrodes. 
- 
Do not apply sensors (including electrodes) to broken or damaged skin. 
- 
Do not autoclave, pressure sterilize, or gas sterilize the CM-1500. 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 22 of 33 
 
- 
Do not soak or immerse the monitor in any liquid. 
- 
Use the cleaning solution, sparingly. The excessive solution can flow into the 
monitor and cause damage to internal components. 
- 
Do not touch, press, or rub the display panels with abrasive cleaning compounds, 
instruments, brushes, rough surface materials, or bring them into contact with 
anything that could scratch the panel. 
- 
Do not use petroleum-based or acetone solutions or other harsh solvents to clean 
the CM-1500. These substances degrade the instrument’s materials, and 
instrument failure may result. 
- 
Do not use damaged sensors and electrodes. Do not use a sensor with exposed 
optical or electrical components. 
- 
Do not immerse sensors in water, solvents, or cleaning solutions (the sensors and 
connectors are not waterproof). Do not sterilize by irradiation, steam, autoclave, or 
ethylene oxide. 
- 
Do not use damaged electrode or trunk cables. 
- 
Do not immerse cables in water, solvents, or cleaning solutions. The patient cable 
connectors are not waterproof. Do not sterilize by irradiation, steam, autoclave, or 
ethylene oxide. 
- 
Do not attempt to reprocess, recondition, or recycle Zynex sensors, electrodes, 
wrist straps, or cables as these processes may damage the components, 
potentially leading to patient harm. 
10.2.4 CONTRADICTIONS: CM-1500 DEVICE 
- 
The CM-1500 is contraindicated for use as an apnea monitor. 
- 
The CM-1500 is contraindicated for patients who have undergone amputation of 
the left upper extremity. 
- 
The CM-1500 is contraindicated for pregnant patients and children. 
- 
The CM-1500 is contraindicated for use in the Magnetic Resonance Imaging (MRI) 
environment. 
- 
The CM-1500 is contraindicated for Dextrocardia. 
10.3 REDUCING RISKS TO A MINIMUM 
Every possible effort will be made to reduce the risks to a minimum. Investigators or 
qualified designated study personnel will be experienced, receive training on the protocol 
and use of the device. All adverse events will be documented and reported to the 
Sponsor. 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 23 of 33 
 
10.4 BENEFITS 
This study is for research purposes only. There is no direct benefit to subjects participating 
in the study. Information from this study may help other people in the future. 
11 SAFETY ASSESSMENT AND MANAGEMENT  
11.1 SAFETY PARAMETERS 
Safety will be assessed by summarizing adverse events. 
11.2 MEDICAL DEVICE REPORTING 
The Sponsor will follow internal Standard Operating Procedures.  
11.3 SAFETY DEFINITIONS 
11.3.1 ADVERSE EVENT (AE)  
An Adverse Event (AE) is defined as any untoward medical occurrence, whether or not 
related to the device or investigational procedure(s). AE’s are characterized by grading, 
actions taken, relationship to the investigation, and outcome. These definitions are 
defined in the corresponding tables below. 
Table 3: Adverse Event Severity Grading 
Severity 
Description 
Grade 1: Mild 
Awareness of signs or symptoms, but they are easily tolerated 
Grade 2: Moderate 
Enough discomfort to cause interference with usual activity 
Grade 3: Severe 
Incapacitating, with the inability to work or do usual activity 
 
Table 4: Adverse Events Action(s) Taken  
Action Taken 
Description 
None 
No actions were taken 
Medications 
Subject required medication(s) 
Other Treatment Required 
Subject required other treatment(s) 
Discontinued Study 
Subject was discontinued from the study 
 
Table 5: Adverse Event Relationship to Investigation 
Relationship 
Description 
None 
Causal relationship can be ruled out 
Possible 
Causal relationship is reasonably possible (i.e., the relationship cannot be 
ruled out) 
Definitely  
Causal relationship is certain 
 
Table 6: Adverse Event Outcome 
Outcome 
Description 
Death 
Death was an outcome of the adverse event. 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 24 of 33 
 
Life-Threatening 
Substantial risk of dying at the time of the adverse event or use or 
continued use of the device or other medical product might have resulted 
in the death of the subject. *  
Hospitalization  
(initial or prolonged) 
Admission to the hospital or prolongation of hospitalization as a result of 
the adverse event. ** 
Disability or Permanent 
Damage 
The adverse event resulted in a substantial disruption of a subject’s 
normal ability to conduct normal life functions. 
Congenital Anomaly/Birth 
Defects 
Exposure to a medical product prior to conception or during pregnancy 
resulting in an adverse outcome in the child. 
Other Serious or Important 
Medical Events 
Checked if the event does not meet other outcomes, but the event may 
jeopardize the subject and may require medical or surgical intervention to 
prevent one of the other outcomes. 
Required Intervention to 
Prevent Permanent 
Impairment/damage 
The medical or surgical intervention was necessary to preclude 
permanent impairment of body function or prevent permanent damage to 
a body structure, either situation to be due to the use of a medical 
product. 
 
11.3.2 SERIOUS ADVERSE EVENT (SAE)  
An SAE is defined as an AE that meets any of the following criteria: Fatal or life-
threatening; requires or prolongs in-subject hospitalization; results in persistent or 
significant disability/incapacity; congenital anomaly/birth defect; important medical event. 
AE’s severity grading, action(s) taken, relationship to the investigation, and the outcome 
will all be used for SAE’s. 
*Whereas life-threatening is defined as an event in which the subject was at risk of death 
at the time of the event. It does not refer to an event that hypothetically may have caused 
death if the event was more severe. 
**Whereas in-subject hospitalization is defined as an event in which the subject was 
admitted to the hospital for one or more days, even if released on the same day or an 
emergency room visit, which results in admission to the hospital. Emergency room visits 
that do not result in admission to the hospital should be evaluated for one of the other 
serious outcomes criteria. 
11.3.3 UNANTICIPATED ADVERSE DEVICE EFFECT (UADE)  
An unanticipated adverse service effect is defined by 21 CFR 812.3 as any serious 
adverse effect on the health of safety or 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 investigational plan or application (including 
supplementary plan or application, or any other unanticipated serious problem associated 
with the device that relates to the rights, safety, or welfare of subjects. 
Table 7: Unanticipated Adverse Device Effect Subject Outcome 
Outcome 
(check all that apply) 
Description 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 25 of 33 
 
Death 
Death was an outcome of the adverse device effect. 
Life-Threatening 
Substantial risk of dying at the time of the adverse device effect or use or 
continued use of the device might have resulted in the death of the 
subject. * 
Hospitalization  
(initial or prolonged) 
Admission to the hospital or prolongation of hospitalization as a result of 
the adverse device effect. ** 
Disability or Permanent 
Damage 
The adverse device effect resulted in a substantial disruption of a 
person’s normal ability to conduct normal life functions. 
Congenital Anomaly/Birth 
defects 
Exposure to a medical product prior to conception or during pregnancy 
resulting in an adverse outcome in the child. 
Other Serious or Important 
Medical Events 
Checked if adverse device effect does not meet other outcomes, but the 
effect may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the other outcomes. 
Required Intervention to 
Prevent Permanent 
Impairment/damage 
The medical or surgical intervention was necessary to preclude 
permanent impairment of body function or prevent permanent damage to 
a body structure, either situation to be due to the use of the device.  
*Whereas life-threatening is defined as an event in which the subject was at risk of death 
at the time of the event. It does not refer to an event that hypothetically may have caused 
death if the event was more severe. 
**Whereas in-subject hospitalization is defined as an event in which the subject was 
admitted to the hospital for one or more days, even if released on the same day or an 
emergency room visit, which results in admission to the hospital. Emergency room visits 
that do not result in admission to the hospital should be evaluated for one of the other 
serious outcomes criteria. 
Table 8: Unanticipated Adverse Device Effect 
Device Effect 
Description 
Death 
The device effect resulted in the death of a subject 
Serious Injury 
The device effect resulted in Serious Injury to the subject 
Malfunction 
The device effect resulted in a malfunction 
 
11.4 RECORDS 
Records of events will be recorded in the source document and Case Report Form (CRF). 
In the instance a CRF is used as a source document, it will only be reported in the CRF.  
11.5 SAFETY REPORTING  
Safety reporting begins at the time of verbal Informed Consent and ends at subject study 
completion.  
Investigators shall submit to the Sponsor and to the reviewing IRB a report of any AE’s 
or SAE’s that occur during the study within five (5) working days but no later than ten (10) 
days after the Investigator learns of the event.  

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 26 of 33 
 
Investigators shall submit to the Sponsor and to the reviewing IRB a report of any 
UADE(s) that occur during the study as soon as possible but no later than ten (10) working 
days after the Investigator learns of the effect. Sponsors will evaluate UADE’s. 
11.5.1 REPORTING EVENTS & SAFETY CONTACTS 
Events will be reported, in writing, to the Principal Investigator, Sponsor, and IRB as soon 
as possible but no later than five (5) working days after the Investigator learns of the 
event. In an event resulting in the death of the subject, the event will be reported within 
24-hours of knowledge of the event.  
Table 9. Safety Reporting Contacts 
Contact 
Contact Information 
Principal Investigator 
Ashish Khanna, MD, FCCP, FCCM 
Wake Forest School of Medicine, Associate Professor 
E: AKhanna@wakehealth.edu 
P: (336) 716-4498 
Sponsor Representative 
Zynex Monitoring Solutions 
E: Clinical@zynex.com 
P: (800) 495-6670  
Institutional Review 
Board 
Wake Forest University Health Sciences 
Office of Research Institutional Review Board 
Medical Center Boulevard 
Winston-Salem, NC 27157-1023 
P: (336)716-4542 
F: (336) 716-4480 
Mailing Address 
Zynex Medical 
Att: ZMS Clinical 
9555 Maroon Circle 
Englewood, CO 80112 
 
12 STATISTICAL METHODS AND CONSIDERATIONS 
12.1 SAMPLE SIZE DETERMINATION 
The sample size of up to 200 subjects was determined feasible.  
12.2 DATA SETS ANALYZED 
All eligible subjects who completed Screening and used the device will be included in the 
analysis. Subjects who withdraw after Screening and before device use will be excluded.  
12.3 DEMOGRAPHIC AND BASELINE CHARACTERISTICS 
The following will be summarized: age, sex, race, ethnicity, height, and weight.  
12.4 STATISTICAL ANALYSIS PLAN (SAP) 
The majority of evaluations pertaining to the performance of the CM-1500 device will 
examine the behavior the Relative Index value in accordance with subject outcomes and 
conditions that present following operatory procedures. The SAP however, can include 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 27 of 33 
 
investigation into individual vital sign parameters that the CM-1500 device (or another 
source) produces during a subject’s recovery. 
Analysis of data sets collected from all subjects aim to satisfy the following purposes, 
included but not limited to: 
• Examine, on a case by case review basis, the results produced by the CM-1500 
device for relevant subject case results. This could include analyzing data and 
comparing produced information to expected/observed information as a result of 
this trial, from either the CM-1500 device or from the principal investigator or from 
additional observers. 
• Classify aggregate results by subject outcomes, particularly nominal and 
hemhoragic shock/complications, and evaluate the performance of the CM-1500 
to indicate either the presence of the presenting complication, or specify the 
absence of presenting complications. 
• Investigate statistical relevance of aggreate subject outcomes (where applicable 
for similar resulting outcomes and/or presenting complications), with analytic  
components possibly including but not limited to: 
o Determination of the sensitivity for the CM-1500 device to identify 
presenting complications, resulting from the performed operatory 
procedure, particularly cases of hemhorage and the related compensatory 
shock. 
o Determination of the specificity of the CM-1500 device to identify normal 
recovery conditions of a subject after the performed operatory procedure 
where no cases of hemhorage, related shock, or other complications 
present. 
o Examination of aggregate data patterns based on the severity and rate of 
complications presenting in subjects. 
o Compilation of relevant trends and patterns, including applicable metrics 
such as mean, max/min, standard deviation, expected linear trajectories, 
etc. of the Relative Index data results for aggregate data, as classified by 
patient outcomes.  
• Evaluate the efficacy of the CM-1500 device for use as an early-detection principle 
method for monitoring changes in fluid volume, not limited to external blood loss, 
particularly in comparison to existing current methods used for evaluating 
hemhoragic shock, fluid inbalance, and other similar presenting conditions. 
 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 28 of 33 
 
13 DATA COLLECTION, RETENTION, AND MONITORING  
13.1 DATA COLLECTION 
The Investigator will prepare, maintain, and retain complete, current, accurate, organized, 
and legible Source Documents to record all observations and other pertinent data for each 
subject. Study personnel will enter data from source documents to protocol-specific 
electronic Case Report Forms (eCRF) or paper CRF. In some instances, CRF’s will serve 
as source documentation. Corrections of data on paper CRFs or source documents will 
be made by crossing out the incorrect data and making the correction. Each correction 
will be initialed and dated by the study personnel making the correction.  
All Investigators are responsible for the information collected on subjects enrolled in the 
study. All data collected during the study must be reviewed and verified for completeness 
and accuracy by the Investigator. If any corrections are made after the Investigators 
signature, the Investigator will also initial and date the correction. 
13.1.1 SUBJECT CONFIDENTIALITY 
In order to maintain subject confidentiality, records identifying the subject will be kept in 
a safe and secure location; access to these records will be on a limited basis. Only the 
subject number, subject sex, subject age or year of birth will identify study subjects on 
CRFs and other documentation submitted to the Sponsor. A limited number of Sponsor 
representatives may have access to limited identifiable information and will take 
reasonable precautions to maintain the confidentiality of the subject’s identity. 
13.2 DATA RETENTION 
All study records will be stored in a safe and secure location. Records will be retained per 
applicable regulatory requirements, which include for a period of 2 years after the latter 
of the following two days: the date which the investigation is terminated or completed, or 
the date that records are no longer required for purposes of supporting premarket 
approval applications or a notice of completion of a product development protocol. The 
Investigator site may transfer custody or records to the Sponsor with appropriate 
documentation recording the transfer. 
13.3 MONITORING 
13.3.1 MONITORING PLAN 
Monitoring visits will be conducted by representatives of the Sponsor or study site or both 
according to 21 CFR 812. (c) for non-significant risk device studies and ICH Guidelines. 
By signing this protocol, the Investigator grants permission to the Sponsor (or designee) 
and all appropriate regulatory authorities to conduct on-site or electronic monitoring or 
auditing or both of all appropriate study documentation. 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 29 of 33 
 
14 STUDY ADMINISTRATION 
14.1 AUDITS AND INSPECTIONS 
External auditors and government inspectors may evaluate the study and must be 
allowed access to CRFs, source documents, and other study files. Audit reports will be 
confidential.  
14.2 PROTOCOL 
14.2.1 STRUCTURE 
The header of IRB approved documents will contain IRB Approval dates and amendment 
information. The footer, specifically, “Form” and “REV” are associated with template 
information, not IRB amendments.  
14.2.2 PROTOCOL AMENDMENTS 
Sponsor approval is required for any protocol amendment. Protocol amendments will not 
be implemented without prior written IRB approval except as necessary to eliminate 
immediate safety hazards to subjects. A protocol amendment intended to eliminate an 
apparent immediate hazard to subjects may be implemented immediately, provided IRBs 
are notified within five (5) working days. The Informed Consent form will be reviewed at 
the time of the protocol amendment.  
14.2.3 PROTOCOL DEVIATIONS 
A protocol deviation is defined as any accidental or unintentional changes to, or non-
compliance with the IRB approved research protocol. Any deviation from the protocol 
must be documented and reported to the Sponsor within 10 working days and reported 
to the IRB as applicable to regulatory requirements. Protocol deviations that pose an 
immediate risk or significant hazard to subjects must be reported to the Sponsor within 
24 hours and reported to the IRB no later than 5 working days after the emergency 
occurred. In the instance, an Investigator uses a device without obtaining informed 
consent; the Investigator shall report to the Sponsor and the IRB within 5 working days 
as per 21 CFR 812.150 (1) (5).  
14.3 INFORMED CONSENT FORM (ICF) AMENDMENTS 
Sponsor approval is required for any ICF Amendment. ICF Amendments will not be 
implemented without prior written IRB approval. 
15 ETHICAL AND OTHER REGULATORY CONSIDERATIONS 
It is the responsibility of the Investigator that the study is conducted according to the 
Declaration of Helsinki, Protection of Human Volunteers (21 CFR 50), Institutional Review 
Board (21 CFR 56), and Responsibilities of Clinical Investigators (21 CFR 812 (e)). 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 30 of 33 
 
15.1 INSTITUTIONAL REVIEW BOARD (IRB) / ETHICS COMMITTEE (EC) REVIEW 
The Protocol, ICF, and any subject facing material will be reviewed and approved by the 
IRB/EC prior to study initiation. Amendments to the Protocol, ICF, or any subject facing 
material will not be implemented without prior written IRB approval unless to eliminate an 
apparent immediate hazard to subjects. AE’s and Protocol Deviations will be reported as 
applicable to the IRB and Sponsor. All IRB approvals will be kept in the Trial Master File, 
Investigator Site File, and copies will be sent to the Sponsor. 
IRB Name: 
Wake Forest University Health Sciences 
Office of Research Institutional Review Board 
IRB Address: 
Wake Forest University Health Sciences 
Office of Research Institutional Review Board 
Medical Center Boulevard 
Winston-Salem, NC 27157-1023 
IRB Phone: 
(336)716-4542 
IRB Email: 
Not Applicable 
IRB Registration #: 
IORG0000129 
Federalwide Assurance #: 
FWA0000143 
 
15.2 INFORMED CONSENT WITH WAIVER OF DOCUMENTATION 
The Informed Consent Form (ICF) and Informed Consent process will include all elements 
required by applicable regulations. Informed consent will be obtained in accordance with 
the Declaration of Helsinki, ICH, Good Clinical Practice, and US Code of Federal 
Regulations for Protection of Human Subjects (21 CFR 50.25 [a,b], CFR 50.27, and CFR 
Part 56, Subpart A), the Health Insurance Portability and Accountability Act (HIPAA) when 
applicable, and local regulations.  
A waiver of documentation is requested as the protocol meets 45 CFR 46.117(c)(1)(ii). 
The research is minimal risk, and a very limited protected health information (“PHI”) will 
be collected as part of this study. De-identified verbal consent will be documented by the 
Investigator or qualified designated study personnel. 
Assent will not be permitted as subjects must be over the age of 18 to meet the 
Inclusion/Exclusion criteria. Legally Authorized Representatives will not be permitted as 
subjects must have the ability to provide verbal consent to meet the Inclusion/exclusion 
criteria.   
16 REFERENCES 
1. Mañas-Gómez MJ, Rodríguez-Revuelto R, Balsells-Valls J, et al. Post-
pancreaticoduodenectomy hemorrhage. Incidence, diagnosis, and 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 31 of 33 
 
treatment. World J Surg. 2011;35(11):2543-2548. doi:10.1007/s00268-011-1222-
4 
2. Ansari D, Tingstedt B, Lindell G, Keussen I, Ansari D, Andersson R. Hemorrhage 
after Major Pancreatic Resection: Incidence, Risk Factors, Management, and 
Outcome. Scand J Surg. 2017;106(1):47-53. doi:10.1177/1457496916631854 
 
 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 32 of 33 
 
Appendix A. Device Unpacking and Inspection Form 
 
THIS APPENDIX IS TO BE USED FOR REFERENCE ONLY.  
PLEASE USE THE DEVICE UNPACKING & INSPECTION TEMPLATE PROVIDED TO 
YOU BY THE SPONSOR. 
 
 
 
 
 

 
CLINICAL PROTOCOL 
SPONSOR: ZMS 
PROTOCOL: ZMS-1500-2001 
  Version 5/13/2021    
 
 
  
 
Form: 10232 
REV: 1.1 
CONFIDENTIAL 
Page 33 of 33 
 
Appendix B. Device Accountability Log 
 
THIS APPENDIX IS TO BE USED FOR REFERENCE ONLY.  
PLEASE USE THE DEVICE ACCOUNTABILITY LOG TEMPLATE PROVIDED TO 
YOU BY THE SPONSOR.