Quantifying the Venous Congestion Curve of a Tissue Oximetry Device
Phase: NA
Conditions: Post-Op Complication, Skin Flap Necrosis
Sponsor: Wake Forest University Health Sciences

Official Title: Quantifying the Venous Congestion Curve of a Tissue Oximetry Device
NCT05592145
IRB-Approved Date: 10/27/23

Study Title: Quantifying the Venous Congestion Curve of a Tissue Oximetry Device  
 
Principal Investigator:  
Ramon Llull, MD  
Plastic and Reconstructive Surgery  
Wake Forest School of Medicine  
rllull@wakehealth.edu 
 
Co-Investigator 
Donald T. Browne, MD 
Plastic and Reconstructive Surgery  
Wake Forest School of Medicine  
dbrowne@wakehealth.edu 
 
Co-Investigator 
Cassandra Driscoll, MD 
Plastic and Reconstructive Surgery  
Wake Forest School of Medicine  
cdriscoll@wakehealth.edu 
 
Co-Investigator  
Joey Kurtzman 
Plastic and Reconstructive Surgery  
Wake Forest School of Medicine  
jkurtzma@wakehealth.edu 
 
 
Sponsor or Funding Source: Departmental, Commercial: (ViOptix, Newark, California) ViOptix will be 
providing a portable ViOptix terminal and sensors for the project.  
 
Background, Rationale, and Context  
 
Transcutaneous oximetry monitoring, which utilizes near infrared spectroscopy (NIRS) 
technology, is one of many modalities in existence to monitor the post-operative circulatory status of 
microvascular skin flap reconstruction1. Specifically NIRS devices such as the ViOptix T.Ox Tissue 
Oximeter (Newark CA.) have the ability to detect vascular compromise in microsurgical flaps prior to 
gold standard techniques such as serial clinical exam and handheld doppler2. The ViOptix T.Ox machine 
utilizes NIRS to measure the oxygenation of composite tissue. The technology is able to assess the 
oxygenation of a piece of tissue with chromophore – this reads a percent tissue oxygenation (StO2). 
 
Success rates of microsurgical procedures has increased in recent years but complications still 
exist. The most common reason for flap failure is vascular thrombosis, and venous thrombosis occurs 
three times more often in free flaps than arterial occlusion3,4. Additionally the success rate of flap 
salvage is higher for venous congestive problems when compared to arterial complications3. Larger scale 
studies have also been conducted which demonstrate the use of ViOptix monitoring can improve flap 
salvage rates and decrease the rate of total flap loss 2,5,6. Although technique improvements have 
decreased complications, microvascular complications such as venous congestion still routinely occur 
post operatively in free flap procedures. Most free flap microvascular complications occur within the 

first 48 hours 3. These complications often result in surgical re-exploration and increased expense to the 
subject7.  
 
Close monitoring remains essential to free tissue transfer success, and timing of intervention 
increases chance of successful salvage if problems arise. Previous studies in the plastic surgery literature 
have retrospectively analyzed data and determined certain tissue oxygenation patterns may exist in 
compromised skin flaps2. However, these samples of data are in a very limited number of patients. Keller 
suggests that an absolute drop of StO2 of 20% in an hour or an absolute StO2 reading below 30% 
indicates flap compromise 2. This criteria may still produce false positives leading to patients returning to 
the OR without microvascular complication 6.  
 
The body of research on NIRS and non-invasive free flap monitoring has grown significantly in 
recent years. To our knowledge these studies have not been able to describe an inflection point or a 
specific pattern which characterizes the venous congestion curve. Identifying these specific patterns will 
help to establish an evidence-based approach in recognizing specific problems and patterns associated 
with tissue compromise that can guide physicians to consider earlier flap salvage measures.  
 
Objectives 
 
We hypothesize the rate of decline and pattern seen in tissue oxygenation as quantified by a 
NIRS device (ViOptiox T.Ox) can be quantified and described by a mathematical model which will allow 
earlier detection and identification of venous congestion in tissue. The vascular occlusion test has been 
established as a safe and accurate model to induce various states of vascular insufficiency and occlusion 
8–15. Specifically the vascular occlusion test has been demonstrated to be an accurate model for inducing 
venous insufficiency on awake and aware patients 14. This study will aim to analyze the StO2 data output 
of the ViOptix in order to establish the earliest signs of tissue failure in various states of vascular 
compromise. 
 
 
Methods and Measures  
 
Design:  
Subjects will be recruited through convenience sampling. Subjects will be given a study number 
at the initiation of the study and will not be identified through any identifying information throughout 
the study.  
 
First, participants included will enter an examination room in the Department of Plastic and 
Reconstructive Surgery clinic. Subjects will be acclimatized for a minimum of 10 minutes before 
commencing the study. After 10 minutes of acclimatization, subjects will have their baseline vitals 
measured and recorded, including heart rate, temperature, blood pressure, height, weight, and BMI.  
Their blood pressure will be taken once on each arm to determine the baseline blood pressure.   The 
variables to be measured and recorded will be pulse oximetry (SpO2), transcutaneous oximetry (StO2), 
demographic information, and past medical history.  
 
The ViOptix machine has the capability to measure two StO2 values simultaneously.  Two ViOptix 
sensor probes will be secured to the subject, one over the volar forearm and one on the volar hand. The 
recording process on the ViOptix machine will begin, and obtain baseline StO2 levels for 5 minutes. After 
5 minutes of baseline measurements the vascular occlusion test will be initiated.  A blood pressure cuff 
will be inflated on one upper extremity in order to occlude venous outflow from the extremity. Venous 

flow is reasonable occluded 20mmHg below systolic blood pressure. The cuff will thus not be inflated 
past the systolic pressure. This blood pressure cuff will be left inflated at a constant pressure for 10-20 
minutes or as long as the subject can tolerate. Every 2 minutes a pulse check or doppler exam will be 
performed at the radial artery to ensure the arterial flow is present. For the duration of the vascular 
occlusion test the desired variables of SpO2, StO2 will be measured and recorded. The ViOptix machine 
continuously records StO2 data. Every 2 minutes during the vascular occlusion test SpO2 will be recorded.  
The cuff will be deflated and the subject will be free to leave the study room. 
 
Setting:  
The study will be conducted in a clinic room of the Department of Plastic and Reconstructive surgery. 
Subjects will include volunteers who meet inclusion/exclusion criteria and provide written informed 
consent for application of upper extremity tourniquet and monitoring by near infrared spectroscopy.  
 
Subjects Selection Criteria  
 
 
To be included in this study it is required that human subject participants are between 18 and 65 years 
of age and meet the following inclusion/exclusion criteria.  
 
Inclusion Criteria 
 
Age 18 – 65 volunteers 
 
Exclusion Criteria  
 Subjects with a history of major cardiac disease, peripheral vascular disease 
including (vascular insufficiency), Raynaud syndrome, blood dyscrasias, pain 
syndromes, neurologic conditions, major upper extremity soft tissue trauma or 
previous vascular injury,  
 
Sample Size  
To ensure the study is adequately powered, we aim to include 40 subjects in the study. We will 
terminate data collection if 100 subjects undergo data collection process.  
 
The number of subjects recruited has been determined by an a priori sample size calculation using 
the statistical software G*Power. Alpha will be set at 5% and beta at 20%. The necessary sample size 
will be determined based on previously collected data regarding the means and standard deviations 
of the measured variables, transcutaneous oximetry number in experimental and control conditions.  
Based on a previous pilot study we anticipate a large effect size in our data gathering. Given these 
previously researched values and effect size an early statistical sample size estimate using G*Power 
suggests a sample size of 32 subjects achieve statistical significance, however we will plan to enroll 
up to 40 subjects.  
 
 
Interventions and Interactions 
1. All identifying information will be removed from subject data collection forms 
2. Anticipated data collection measures include but are not limited to age, gender, height, weight, 
BMI, vitals, O2 saturation, TCOM, and past medical history.  
 

The T.OxTM device has 2 small monitors at the end of fiber optic cables that are placed on the skin of a 
patient. It is normally used after surgery to be placed on a patient directly on or near their surgical area 
to remain there for 48 hours post-operatively. For that intended use, The T.OxTM sensor is packaged as a 
sterile device and is intended for single-use in a sterile environment. For this study however, the 
monitors are being placed on the wrists of patients with no surgical interventions. The monitors will 
remain on for only the length of the study visit (~35min) as opposed to 48 hours after a surgery. 
 
Because this is a non-significant risk study for non-invasive data collection only, we plan to re-use the 
sterile T.OxTM sensor on multiple subjects with appropriate cleaning (Sani Cloth AF3 wipe) between uses 
as with any non-sterile device used on multiple subjects. The device will be allowed to dry for 3 minutes 
per instructions. This wipe has shown effectiveness against SARS-CoV-2. 
 
 
Outcome Measures 
We will collect de-identified data including age, gender, BMI. WE will collect vital signs prior to initiation 
of vascular occlusion test. Additionally, we will collect tissue oxygenation values from the ViOptix 
terminal, and oxygen saturation via pulse oximetry. The main outcome measure will be the change in 
StO2 over time of vascular occlusion test.  
 
Analytical Plan 
We will initially use descriptive statistics to quantify and describe the results.  We will aim to analyze the 
rate of change of tissue oxygenation across time to better define the aggregate rate of change. We will 
use descriptive statistics to compare subject demographic data.  
 
Human Subjects Protection  
There will be no identifying subject information included in data collection.  Informed consent will be 
required prior to enrollment and initiation of the study. Subjects will be provided informed consent and 
given the option to participate in the study or decline. All data will be de-identified and there will be no 
way to link data collection to specific subject. Subjects and characteristics will be identified by a 
generated code for database codification.  
  
Subject Recruitment Methods  
Subjects for the study will be recruited via convenience sampling.  A minimum of 32 subjects at WFBMC 
will be recruited for the study. A face to face interaction will occur in the exam room where the 
potential subject will have the opportunity undergo the informed consent process and decide to 
participate in the study.  If they agree to participate the subject will be enrolled and will proceed with 
data collection after informed consent is obtained. 
 
Informed Consent  
Signed informed consent will be obtained from each subject. Informed consent will be obtained after 
the study has been fully explained to each subject and all questions and concerns have been properly 
addressed. The investigators or a member of the study team will obtain informed consent. Informed 
consent will take place in a private examination area of Plastic and Reconstructive Surgery clinical areas. 
After signing the ICF, the subject will be given a signed copy. 
  
Confidentiality and Privacy  

Confidentiality will be protected by collecting only de-identified information needed to assess study 
outcomes, thus any information that could directly identify subjects. The de-identified database will be 
kept in a secure excel file on the Plastic Surgery Drive on the WFBMC network. Identities will not be 
saved on data collection forms. We will be producing an producing an anonymous analytical data 
set.  Data access will be limited to study staff.  Data and records will be kept locked and secured, with 
any computer data password protected.  No reference to any individual participant will appear in 
reports, presentations, or publications that may arise from the study. The planned data to be collected 
will not include any of the 18 personal identifiers set forth by HIPAA. 
  
Data and Safety Monitoring  
The principal investigator will be responsible for the overall monitoring of the data and safety of study 
participants.  The principal investigator will be assisted by other members of the study staff. 
  
Reporting Unanticipated Problems, Adverse, Events, or Deviations  
Any unanticipated problems, serious and unexpected adverse events, deviations or protocol changes 
will be promptly reported by the principal investigator or designated member of the research team to 
the IRB and sponsor or appropriate government agency if appropriate. 
  
 
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Keller A. A new diagnostic algorithm for early prediction of vascular compromise in 208 
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