Accuracy of the NICCI™ Monitor in Providing Beat-to-beat Non-invasive Blood Pressure Readings in Children and Adolescents
Phase: NA
Conditions: Surgery, Anesthesia
Sponsor: Joseph D. Tobias

 
 
Accuracy of the NICCI™ monitor in providing beat-to-beat non-
invasive blood pressure readings in children and adolescents 
 
 
 
 
 
NCT04373746 
 
 
 
 
 
April 20, 2020 
 
 

PROTOCOL TITLE: Accuracy of the NICCI™ monitor 
 
 
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HRP-503  v.12.10.18 
 
 
PROTOCOL TITLE: Accuracy of the NICCI™ monitor in providing beat-to-beat 
non-invasive blood pressure readings in children and adolescents 
 
PRINCIPAL INVESTIGATOR: 
Name: Joseph Tobias, MD 
Department/Center: Anesthesiology & Pain Medicine 
Telephone Number: 614-722-4200 
Email Address: Joseph.Tobias@nationwidechildrens.org 
 
VERSION NUMBER/DATE: Version 1.1 - April 20, 2020 
 
REVISION HISTORY 
 
Revision 
# 
Version Date 
Summary of Changes 
Consent Change? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

PROTOCOL TITLE: Accuracy of the NICCI™ monitor 
 
 
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HRP-503  v.12.10.18 
1.0 
Study Summary 
 
Study Title 
Accuracy of the NICCI™ monitor in providing beat-to-beat non-
invasive blood pressure readings in children and adolescents 
Study Design 
Prospective, non-blinded comparative study 
Primary Objective 
The primary objective of this study is to compare the blood pressure 
reading (systolic, diastolic, and mean) from an arterial cannula with 
the readings obtained from the non-invasive continuous blood 
pressure monitoring, NICCI™ 
Secondary Objective(s) 
None 
Research Intervention(s)/ 
Investigational Agent(s)  
Measuring beat-to-beat blood pressure non-invasively with the 
NICCI™ monitor. There will be no change in anesthetic 
management or use of investigational pharmacological agents.    
IND/IDE #  
Not applicable 
Study population 
Patients who are scheduled for elective, urgent or emergent surgery 
Sample size 
150 (50 in each of 3 weight groups 10-20 kg, 20-40, and ≥ 40 kg) 
Study duration for 
individual participants 
Duration of the surgical procedure (2-10 hours) 
Study Specific 
Abbreviations/ Definitions  
BP = blood pressure 
sBP = systolic blood pressure 
dBP = diastolic blood pressure 
MAP = mean arterial pressure 
NIBP = non-invasive blood pressure 
IBP = intra-arterial blood pressure 
 
2.0 
Objectives 
2.1 The primary objective of this study is to compare blood pressure (BP) 
readings obtained from an invasive arterial cannula and a non-invasive 
continuous BP device. The hypothesis is that this novel non-invasive device 
will provide an accurate and continuous estimation of BP. 
 
3.0 
Background 
3.1 BP is one of the most important parameters in several clinical settings. 
Particularly during the perioperative period, BP needs to be monitored 
repeatedly or even continuously to facilitate the best care for patients. This is 
done either intermittently using an oscillometric non-invasive blood pressure 
device (NIBP) or continuously by an invasive arterial line (IBP). A number 
of clinical studies show that both methods may have pitfalls and at times be 
inaccurate. Since the NIBP provides discontinuous pressure readings with the 
current recommendations for intraoperative monitoring stating that the BP 
should be monitored every 5 minutes, hemodynamic events may be missed or 
there may be a delay in recognition of alterations in BP.  Therefore, during 
major intraoperative procedures in patients with co-morbid cardiac diseases 
or during procedures with significant blood loss, invasive arterial monitoring 
of BP is chosen with placement of an intra-arterial cannula.  Although 
generally safe and effective, the placement of an intra-arterial cannula may be 

PROTOCOL TITLE: Accuracy of the NICCI™ monitor 
 
 
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HRP-503  v.12.10.18 
associated with complications including artery occlusion with distal ischemia, 
hematoma formation, blood loss due to unintended disconnection, infection 
or nerve damage with sensory disturbance.  More importantly, arterial 
cannulation takes time and may at times be impossible. Therefore, a method 
that non-invasively allows the continuous measurement of BP would be 
clinically useful. 
 
3.2 The NICCI, Pulsion/GETINGE uses novel technology to provide a 
continuous estimation of BP displayed as a waveform similar to that seen with 
an invasive arterial cannula (information attached).  Infrared (IR) light, 
emitted from a Light Emitting Diode, is sent through the finger. The light is 
partly absorbed by the arterial blood, which is changing according to the heart 
activity (pulse). A light detector receives the remaining light on the other side 
of the finger and thus detects the continuous pulse signal. Counter pressure is 
exerted from the outside in such a way that the arterial wall is totally unloaded. 
This continuously changing outside pressure keeps the arterial blood volume 
constant at all times and directly corresponds to the arterial pressure. The 
intra-arterial pressure is therefore measured indirectly. To calibrate the 
continuous pulse-contour curve with the correct absolute blood pressure 
values, an automatic non-invasive blood pressure (NIBP) measurement is 
either performed on the patient’s upper arm or provided by the user. This 
device is based on technology original developed as the CNAP™ monitor 
which has been tested and validated by us previously in other IRB-approved 
trials. 
21 
Dewhirst E, Corridore M, Klamar J, Beebe A, Rice 
J, Barry S, Tobias JD. Accuracy of the CNAPTM monitor, a 
noninvasive continuous blood pressure device, in providing 
beat-to-beat blood pressure readings in the prone position.  
J Clin Anesth 2013;25:309-313. 
22 
Kako H, Corridore M, Rice J, Tobias JD.  Accuracy 
of the CNAPTM monitor, a non-invasive continuous blood 
pressure device, in providing beat-to-beat blood pressure 
readings in pediatric patients weighing 20 to 40 kilograms.  
Pediatric Anesth 2013;23:989-993. 
23 
Tobias JD, McKee, Herz D, Teich S, Sohner P, Rice 
J, Barry N, Michalsky M.  Accuracy of the CNAPTM 
monitor, a non-invasive continuous blood pressure device, 
in providing beat-to-beat blood pressure measurements 
during bariatric surgery in severely obese adolescents and 
young adults.  J Anesth 2014;28:861-865. 
 
 
4.0 
Study Endpoints 
4.1 The primary study endpoint is to compare the BP readings from the non-
invasive NICCI device with those obtained from an arterial cannula. 
 

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HRP-503  v.12.10.18 
5.0 
Study Intervention/Investigational Agent 
5.1 The only novel intervention is the use of the NICCI device to monitor blood 
pressure. No change in the anesthetic technique will be required during the 
study. The study will include only patients scheduled for a surgical procedure 
that requires invasive monitoring of arterial blood pressure (placement of an 
arterial cannula). 
 
6.0 
Procedures Involved* 
6.1 This is a prospective study that will compare the blood pressure 
readings from an arterial cannula with those obtained non-invasively 
by the NICCI device. The study will enroll 50 patients into each of 
three weight ranges: 10-20 kg, 20-40 kg, and 40-80 kg. 
 
6.2 The study cohort will include patients requiring anesthetic care and in 
whom an indwelling arterial cannula will be placed for the surgical 
procedure.  The arterial cannula will not be placed for the purpose of 
the study.  The NICCI™ monitor will be attached to the patient and 
simultaneous readings from the NICCI™ monitor and the invasive 
arterial cannula will be downloaded every minute into a laptop 
computer for later analysis. 
 
6.3 Exclusion criteria: 
• Patients with history of a peripheral neurologic or 
neuropathic disorder 
• Patients in whom the upper extremity cannot be used for 
blood pressure monitoring 
• Patients in whom an invasive arterial cannula cannot be 
placed 
• Patients with vascular implants at the sites of non-invasive 
blood pressure measurement (fingers and upper arm of the 
examined arm) 
• Edematous patients 
 
6.4 There are no foreseeable risks associated with the use of NICCI™ 
device.  
 
6.5 The data (BP readings) will be downloaded into a bedside NCH 
laptop in the operating room and stored on our password-secured 
server. 
 
7.0 
Data and Specimen Banking* 
N/A 
 
8.0 
Sharing of Results with Subjects* 
8.1 Results will not be shared with subjects. 

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HRP-503  v.12.10.18 
 
9.0 
Study Timelines* 
9.1 An individual study subject’s participation in the study should last 2-
10 hours depending on the duration of the surgical procedure. 
9.2 All study subjects should be enrolled within 1 year of the start of the 
study. 
9.3 The study data will be analyzed, a manuscript written, and the study 
completed within 18 months of the start of the study. 
 
10.0 Inclusion and Exclusion Criteria* 
10.1 Potential subjects will be identified by reviewing the surgery 
schedule in Epic and will be recruited from the main OR pre-
operative area the day of their surgery. 
10.2 Inclusion criteria: ASA 1-4 patients, weighing 10 to 80 kg 
undergoing a surgical procedure with general anesthesia and 
requiring an invasive arterial cannula.  
10.3 Exclusion criteria: 
• Patients with history of a peripheral neurologic or neuropathic 
disorder 
• Patients in whom the upper extremity cannot be used for blood 
pressure monitoring 
• Patients in whom an invasive arterial cannula cannot be placed 
• Patients with vascular implants at the sites of non-invasive blood 
pressure measurement (fingers and upper arm of the examined 
arm) 
• Edematous patients 
 
11.0 Vulnerable Populations* 
11.1 We will include children, and will not include adults, pregnant woman, and 
prisoners as they are not part of our usual patient population. 
 
12.0 Local Number of Subjects 
12.1 150 (50 in each weight range of routine, urgent, and emergent cases).  
 
13.0 Recruitment Methods 
13.1 Potential subjects will be recruited in the surgical preoperative area 
on the day of the surgery. The research team will contact the 
guardian/parents and obtain consent.  Assent will also be obtained 
from age appropriate patients. 
13.2 The patients to be recruited are those who are scheduled for surgery 
under general anesthesia in the NCH operating rooms. 
13.3 Using Epic, the research team will check the patients scheduled for 
planned surgery in the NCH operating rooms. 
 
14.0 Withdrawal of Subjects* 

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Patients may withdraw from the study at any time.  
 
15.0 Risks to Subjects* 
15.1 Although not likely, there may be a potential risk for breach of patient 
health information. There is no study related physical risk to study 
subjects associated with this study. All study related procedures are 
non-invasive. 
 
15.2 Subject information will not be given to any other investigators. 
Subjects and their information will be closely monitored and guarded 
by study staff; there will be limited access to patients and their 
information by trained study staff; and subject information will only 
be shared and discussed between study staff specific to this study. 
Subject PHI will be stored in a locked cabinet, and will be stored and 
maintained in password protected computer files. 
 
16.0 Potential Benefits to Subjects* 
16.1 There are no specific immediate benefits to the patient. 
 
17.0 Data Management* and Confidentiality 
17.1 Statistical analysis and data presentation will include a calculation 
of the absolute difference of the sBP, dBP and MAP values of the 
two devices.  To avoid biasing the data, the absolute not directional 
difference will be used.  For example, if the reading from NICCI™ 
device was 10 mmHg above or below the reading from the AL, a 
value of 10 mmHg was used, not -10 or +10 mmHg.  Additionally, 
a determination will be made of the percentage of values from the 
NICCI™ device that are ≤ 5 mmHg and more than 10 mmHg from 
the IBP values.  A Pearson correlation coefficient will be calculated 
comparing the sBP, dBP and MAP values between the arterial 
cannula and the NICCI™ device.  A Bland-Altman analysis with 
multiple measurements per subject will be performed to determine 
the bias and 95% level of agreement for the three groups. 
 
17.2 De-identified data will be shared with the manufacturer of the 
monitor, Getinge.  They will be assisting with data analysis, as well 
as, using the data for a 510(K) submission to the FDA. 
 
17.3 Research records will be stored in a locked cabinet and password 
protected computer.  Only certified research personnel will be given 
access to identifiable subject information 
 
17.4 Following publication of study results, research records will be 
stored for a period of 5 years and then will be destroyed by placing 
in a secure shredding bin. 
 

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18.0 Provisions to Monitor the Data to Ensure the Safety of Subjects* 
The study will only be monitored by the study investigators. 
 
19.0 Provisions to Protect the Privacy Interests of Subjects 
19.1 Subject information will not be given to any other investigators. 
Subjects and their information will be closely monitored and guarded 
by study staff; there will be limited access to patients and their 
information by trained study staff; and subject information will only 
be shared and discussed between study staff specific to this study.  
 
20.0 Compensation for Research-Related Injury 
Not applicable 
 
21.0 Economic Burden to Subjects 
None 
 
22.0 Consent Process 
22.1 The consent process will begin in the preoperative surgery unit on the day 
of surgery, by PI, Sub-Investigators, Study Coordinators, and/or trained research 
staff. 
 
22.2 The study will be thoroughly explained to the patient and their family. 
There will be ample time allotted for questions and answers. An explanation of 
voluntary participation will take place, and the family will be asked if they are 
interested in participating in the study. If the patient and their parent(s), or legal 
guardian agrees to participate they will be asked to sign consent and assent form. 
The patient will then be enrolled in the study with the understanding that they 
can elect to stop the study and be withdrawn from the study at any time.  
 
23.0 Process to Document Consent in Writing 
23.1 We will be following “SOP: Written Documentation of Consent 
(HRP-091).”  
 
24.0 Setting 
Research procedures will be performed in the operating room during 
anesthetic care. 
 
25.0 Resources Available 
25.1 We will need approximately 30 minutes per patient to explain the 
research protocol, obtain consent, and enroll patients. The Department 
of 
Anesthesiology 
and 
Pain 
Medicine 
has 
2 
research 
coordinators/RNs and 2 research associates that will be enrolling 
subjects for this study.  All study staff will be trained regarding the 
study procedures. Before the study starts, the study protocol, the 

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research procedures, research member’s duties, and functions will be 
informed by e-mail and during a pre-study meeting. 
 
26.0 Multi-Site Research* 
Not applicable 
 
27.0  Protected Health Information Recording 
1.0 
Indicate which subject identifiers will be recorded for this research. 
☒  Name 
☐  Complete Address 
☐  Telephone or Fax Number 
☐  Social Security Number (do not check if only used for ClinCard) 
☒  Dates (treatment dates, birth date, date of death) 
☐  Email address, IP address or url 
☒  Medical Record Number or other account number 
☐  Health Plan Beneficiary Identification Number 
☐  Full face photographic images and/or any comparable images (x-rays) 
☐  Account Numbers 
☐  Certificate/License Numbers 
☐  Vehicle Identifiers and Serial Numbers (e.g. VINs, License Plate Numbers) 
☐  Device Identifiers and Serial Numbers 
☐  Biometric identifiers, including finger and voice prints 
☐  Other number, characteristic or code that could be used to identify an 
individual 
☐  None (Complete De-identification Certification Form) 
 
2.0   
Check the appropriate category and attach the required form* on the Local 
Site Documents, #3. Other Documents, page of the application.  (Choose one.) 
☒  Patient Authorization will be obtained. (Include the appropriate HIPAA 
language (see Section 14 of consent template) in the consent form OR attach 
the HRP-900, HIPAA AUTHORIZATION form.) 
☐  Protocol meets the criteria for waiver of authorization. (Attach the HRP-901, 
WAIVER OF HIPAA AUTHORIZATION REQUEST form.) 
☐  Protocol is using de-identified information. (Attach the HRP-902, DE-
IDENTIFICATION CERTIFICATION form.) (Checked "None" in 1.0 above) 
☐  Protocol involves research on decedents. (Attach the HRP-903, RESEARCH 
ON DECEDENTS REQUEST form.) 
☐  Protocol is using a limited data set and data use agreement. (Contact the 
Office of Technology Commercialization to initiate a Limited Data Use 
Agreement. 
 
*Find the HIPAA forms in the IRB Website Library, Templates. 
 

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HRP-503  v.12.10.18 
Attach the appropriate HIPAA form on the “Local Site Documents, #3. 
Other Documents”, page of the application. 
 
3.0    How long will identifying information on each participant be maintained? 
Following publication of study results, research records will be stored for a period 
of 5 years and then will be destroyed by placing in a secure shredding bin. 
 
4.0 
Describe any plans to code identifiable information collected about each 
participant. 
Not applicable. 
 
5.0 
Check each box that describes steps that will be taken to safeguard the 
confidentiality of information collected for this research: 
☒ Research records will be stored in a locked cabinet in a secure location 
☒ Research records will be stored in a password-protected computer file 
☐ The list linking the assigned code number to the individual subject will be 
maintained separately from the other research data 
☒ Only certified research personnel will be given access to identifiable 
subject information 
 
6.0 Describe the provisions included in the protocol to protect the privacy interests 
of subjects, where "privacy interests" refer to the interest of individuals in being 
left alone, limiting access to them, and limiting access to their information. (This 
is not the same provision to maintain the confidentiality of data.)  
Subject information will not be given to any other investigators. Subjects and their 
information will be closely monitored and guarded by study staff; there will be 
limited access to patients and their information by trained study staff; and subject 
information will only be shared and discussed between study staff specific to this 
study. Describe the steps that will be taken to protect subjects’ privacy interests. 
“Privacy interest” refers to a person’s desire to place limits on whom they interact or 
whom they provide personal information. 
 
 
Confidential Health Information 
 
1.0 
Please mark all categories that reflect the nature of health information to be 
accessed and used as part of this research. 
☒  Demographics (age, gender, educational level) 
☒  Diagnosis 
☐  Laboratory reports 
☐  Radiology reports 
☐  Discharge summaries 
☒  Procedures/Treatments received 
☒  Dates related to course of treatment (admission, surgery, discharge) 
☐  Billing information 
☐  Names of drugs and/or devices used as part of treatment 

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HRP-503  v.12.10.18 
☐  Location of treatment 
☐  Name of treatment provider 
☐  Surgical reports 
☒  Other information related to course of treatment 
☐  None 
 
2.0 
Please discuss why it is necessary to access and review the health information 
noted in your response above. 
 
Demographics need to be recorded to describe the patient characteristics of the 
study cohort for publication of these data in scientific journals. Diagnosis and 
procedures need to be assessed for inclusion criteria.  
 
3.0 
Is the health information to be accessed and reviewed the minimal necessary 
to achieve the goals of this research?  ☒ Yes    ☐ No 
 
4.0 
Will it be necessary to record information of a sensitive nature?  ☐ Yes   ☒ 
No 
 
5.0 
Do you plan to obtain a federally-issued Certificate of Confidentiality as a 
means of protecting the confidentiality of the information collected?  ☐ Yes   
☒ No