A Prospective, Randomized Controlled Trial Evaluating the Effectiveness of the Fluid Immersion Simulation (FIS) System Versus Air Fluidized Bed (AFB) System in the Acute Post-Operative Management of Surgically Closed Pressure Ulcers
Phase: NA
Conditions: Pressure Ulcer
Sponsor: Northwestern University

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A Prospective, Randomized Controlled Trial Evaluating the Effectiveness of the Dolphin 
Fluid Immersion Simulation® System versus Air Fluidized Systems in the Acute Post-
Operative Management of Surgically Closed Pressure Ulcers
Purpose: To examine the effectiveness of the Dolphin Fluid Immersion Simulation® System 
compared to air fluidized systems in the acute post-operative management of pressure ulcers
Product: Dolphin Fluid Immersion Simulation® System
Protocol Number: 01.5
Date: 3-1-16
Protocol Version: 1.9
Sponsor: Joerns Healthcare, LLC
IRB #: STU00200584 Approved by NU IRB for use on or after 5/20/2020 through 5/19/2021.

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Contact Information
IRB #: STU00200584 Approved by NU IRB for use on or after 5/20/2020 through 5/19/2021.

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Sponsor Approval
IRB #: STU00200584 Approved by NU IRB for use on or after 5/20/2020 through 5/19/2021.

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Study Synopsis
Sponsor: Joerns Healthcare, LLC                             
Protocol Number: 01.5
Product: Dolphin Fluid Immersion Simulation® System
Regulatory Class: II
Development Phase: Commercialization
Title: A Prospective, Randomized Controlled Trial Evaluating the Effectiveness of the 
Dolphin Fluid Immersion Simulation® System versus Air Fluidized Systems in the Acute 
Post-Operative Management of Pressure Ulcers
Study Design: This study protocol outlines a prospective, randomized controlled post-market 
human subject trial.
Primary Objective: The primary objective is to compare the efficacy of the Dolphin Fluid 
Immersion Simulation® System on closure and complication rates as compared to air fluidized 
support systems after operative debridement and closure. 
Secondary Objectives: 
1.) Comparisons of the inflammatory and bacterial microbiomes of pressure ulcers following 
surgical therapy.
2.) Comparisons of baseline patient characteristics and their relationship to both early and 
late pressure ulcer recurrence, and complication rates. 
3.) Assessment of outcomes and complications associated with flap technique and surgeon 
guided descriptions of the operative closure.  
4.) Compare the absolute costs associated with the Dolphin FIS System against air fluidized 
systems. 
5.) Compare the acceptance of each system by subjects and nursing staff, including the 
parameter of patient comfort. 
6.) Assessing the incidence of complications and additional treatments needed following the 
two week study period
Number of Subjects: 100-200
Study Population: Adults, 18 years of age to 85 years of age, with 2 or fewer pressure ulcers 
and a history of fewer than 3 closures.  
Control Therapy: Standard air fluidized systems
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Duration of Study Participation: 1 year 
Structure: Parallel Group   Duration of Treatment: 2 weeks   Duration of Assessment: 1 year
Blinding: Double-Blind
Randomization: Yes             Group Assignment: 1:1
End Point Criteria Measurements: 
Primary: Success of closure and incidence of wound related dehiscences or flap 
complications within the 2 weeks following operative closure
Secondary: 
1. Bacterial speciation and antibiotic resistance taken just prior to and following the first 
surgical debridement and their subsequent relation to complications and time to 
closure in each group.  
2. Differences in bacterial speciation and antibiotic resistance, total bacterial counts, and 
pressure ulcer microbiome.  Bacterial speciation and antibiotic resistance will be 
determined by quantitative cultures and PCR analysis.  Differences in total bacterial 
counts will be determined by quantitative PCR analysis.  Pressure ulcer microbiome 
will be assayed via PCR assays conducted by PathoGenius Laboratory™.  
Comparisons will be made between biopsies taken prior to and following the initial 
operative debridement, following any subsequent debridements, prior to operative 
closure, and two weeks following definitive closure.  
3. Qualitative and quantitative markers of inflammation in the pressure ulcer utilizing 
protein and PCR assays.  Comparisons will be made between tissue biopsies taken 
prior to and following the initial operative debridement, following any subsequent 
debridements, prior to operative closure, and two weeks following definitive closure.  
4. Evaluation of patient characteristics (age, comorbidities, nutritional parameters, 
spasticity, medications, ulcer history) and their relation to early and late recurrences 
as well as complications.
5. Comparison of outcomes and complication rates based on flap technique and surgeon 
guided descriptions of the operative closure. 
6. Total costs incurred including treatment costs, the costs of associated complications, 
cost of the hospital stay, and any other unforeseen costs during the two week study 
period following operative closure.
7. Differences in quantitative patient and nurse survey responses regarding acceptability 
and tolerance of each therapeutic modality, including patient comfort.
8. Regular follow-up via phone interviews to assess for additional complications and 
need for additional therapies or surgical procedures up to 1 year after surgical closure.
Safety: Adverse events
Adverse Events: Both volunteered and elicited
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Table of Contents
1. Introduction..............................................................................................................................9 
1.1 Background.............................................................................................................9
1.2 Preventative Therapy ............................................................................................10
1.3 Management of Pressure Ulcers ...........................................................................12
1.4 Description of Study Products ..............................................................................17
1.5 Study Rationale.....................................................................................................21
2. Study Objectives.....................................................................................................................22
2.1. Endpoint Criteria Measurements ..........................................................................22
2.1.1. Primary Endpoint...................................................................................22
2.1.2. Secondary Endpoints .............................................................................22
2.1.3. Safety Endpoints....................................................................................24
3. Study Design...........................................................................................................................24
3.1. Overview ..............................................................................................................24
3.2. Duration of Clinical Investigation Participation...................................................26
4. Selection of Subjects ..............................................................................................................28
4.1. Recruitment and Screening...................................................................................28
4.1.1. Subject Stipend ......................................................................................29
4.1.2. Wound Selection....................................................................................29
4.2. Inclusion Criteria ..................................................................................................30
4.3. Exclusion Criteria .................................................................................................30
5. Study Procedures and Treatment.........................................................................................31
5.1. Informed Consent..................................................................................................31
5.2. Screening...............................................................................................................32
5.3. Randomization......................................................................................................33
5.4. Initial OR Debridement of Wound .......................................................................34
5.5. Wound Care Prior to Closure................................................................................35
5.6. Additional OR Wound Debridement ....................................................................36
5.7. Wound Closure or Coverage.................................................................................36
5.8. Two Week Study Period.......................................................................................37
5.9. Follow-Up After Two Week Study Period...........................................................37
6. Study Assessments/Measurement Tools ..............................................................................38
6.1. Quantitative PCR Analysis ...................................................................................38
6.2. Qualitative Aerobic and Anaerobic Cultures........................................................38
6.3. Quantitative Protein Analysis ...............................................................................38
6.4. Laboratory Tests ...................................................................................................39
6.5. Clinical Wound Assessments................................................................................40
6.6. Concomitant Medications and Antibiotic Use......................................................42
6.7. Wound History......................................................................................................43
6.8. Operative Documentation .....................................................................................43
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6.9. Digital Wound Photographs..................................................................................44
6.10. Clinical Acceptance of Treatment Arms.............................................................45
7. Statistical Design....................................................................................................................46
7.1. Statistical Methods Planned..................................................................................47
7.2. Determination of Sample Size ..............................................................................48
7.3. Interim Analysis....................................................................................................48
7.4. Analysis Populations.............................................................................................49
7.5. Efficacy Analyses .................................................................................................49
7.5.1. Primary Efficacy....................................................................................49
7.5.2. Secondary Efficacy................................................................................50
7.6. Safety Analyses.....................................................................................................55
7.7. Handling of Missing and Incomplete Data...........................................................56
8. Study Discontinuation and Withdrawal of Study Subjects ...............................................56
8.1. Premature Discontinuation of the Study...............................................................56
8.1.1. By Sponsor.............................................................................................56
8.1.2. By IRB ...................................................................................................57
8.2. Premature Discontinuation of the Subject ............................................................57
8.2.1. By Investigator.......................................................................................57
9. Potential Risks of Study Participation.................................................................................58
9.1. Potential Risks Associated with the Investigational Product................................58
10. Monitoring for Safety ............................................................................................................59
10.1. Adverse Events ...................................................................................................59
10.2. Serious Adverse Events ......................................................................................60
10.3. Anticipated Events..............................................................................................61
10.4. Investigator Reporting Requirements .................................................................61
10.5. Device Malfunction ............................................................................................62
10.6. Adverse Event Related Withdrawal....................................................................62
10.7. Follow-up of Subjects with Adverse Events.......................................................62
11. Quality Control and Quality Assurance ..............................................................................63
11.1. Training on Study Products and Procedures.......................................................63
11.2. Sponsor ...............................................................................................................63
11.3. Investigator .........................................................................................................64
12. Ethics.......................................................................................................................................64
12.1. Institutional Review Board (IRB).......................................................................64
13. Data Handling and Recording..............................................................................................65
13.1. Data Quality Assurance ......................................................................................65
13.2. Data Collection ...................................................................................................65
13.3. Data Handling.....................................................................................................65
13.4. Record Storage and Retention ............................................................................66
13.4.1. Investigator ..........................................................................................66
13.4.2. Sponsor ................................................................................................66
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14. Confidentiality of the Study..................................................................................................67
15. Publication Policy...................................................................................................................67
16. References...............................................................................................................................68
Table of Tables
Table 1. Scoring Table for Wound Characteristics and Appearance.............................................40
Table 2. Surgeon Guided Scoring of Operative Closure ...............................................................44
Table 3. Nurse Acceptability Scale................................................................................................46
Table 4. Patient Acceptability Scale ..............................................................................................46
Table 5. Definition of Intensity of Adverse Events.......................................................................60
Table 6. Relationship of Adverse Events to the Device ................................................................60
1. Introduction
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1.1 Background
Pressure ulcers are defined by the National Pressure Ulcer Advisory Panel (NPUAP) as 
“localized injury to the skin and/or underlying tissue usually over a bony prominence, as a result 
of pressure, or pressure in combination with shear.”[1]  The epidemiology of pressure ulcers 
varies significantly by clinical care setting, with incidence rates ranging from 0.4% to 38% in 
acute care, 2.2% to 23.9% in long-term care,  and 0% to 17% in home care.[2]  In US acute care 
facilities alone, an estimated 2.5 million pressure ulcers are treated each year.[3]  Coupled with 
the high incidence of pressure ulcers in the US population are the staggering health care costs 
associated with their management.  The cost of managing a single full-thickness pressure ulcer is 
as much as $70,000 per event, and US expenditures for treating pressure ulcers have been 
estimated at $11 billion per year.[4, 5] The recent decision in 2009 by the Centers for Medicare 
& Medicaid Services deeming pressure ulcers reasonably preventable and halting additional 
reimbursement for the treatment of hospital-acquired pressure ulcers, even if clinicians deemed 
them unavoidable, has compounded the fiscal burden associated with pressure ulcer 
management.[6]  The development of pressure ulcers also carries significant legal repercussions. 
Pressure ulcers litigation against long-term care providers has resulted in settlements favoring the 
plaintiffs in up to 87% of cases.[7] 
The risk factors associated with increased risk of pressure ulcer development are broad 
and include older age, black race, lower body weight, physical or cognitive impairment, poor 
nutritional status, incontinence, and specific medical comorbidities that affect circulation such as 
diabetes or peripheral vascular disease.[8-12]  Pressure ulcers are often associated with pain, can 
contribute to functional impairment with delayed returns to function, can lead to complications 
such as infection, and may significantly prolong hospitalizations.[13, 14]  In addition, the 
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presence of pressure ulcers themselves are associated with a poorer overall prognosis and may 
also contribute to mortality risk.[14]
The consequences of pressure ulcer development and management highlight the value in 
devising novel, efficacious, and cost-effective preventative and management strategies. 
1.2 Preventative Therapy
Recommended prevention strategies for pressure ulcers generally involve use of risk 
assessment tools to identify people at higher risk for ulcer formation in conjunction with 
interventions designed to avert ulcer formation.[15, 16]  A number of instruments have been 
developed to assess the risk of pressure ulcer development.  The three most widely used are the 
Braden scale, the Norton scale, and the Waterlow scale.[17-19]  Categories of preventative 
interventions include support surfaces such as mattresses and integrated bed systems, 
repositioning, skin care, and nutritional support with each category encompassing a wide variety 
of diverse interventions.[15, 16]  Prior trials have been limited in that none have evaluated the 
effectiveness of preventative interventions by clinical care setting and patient characteristics.  
Rather, the majority of trials have been conducted based on a priori risk assessments.  
Support surface systems include static mattresses, overlays, or bed systems; or alternating 
air mattresses, overlays, and bed systems.  These devices serve to redistribute pressure in order to 
manage tissue loads, micro-climate, and/or other therapeutic functions.[20]  Results of studies 
investigating these systems have been equivocal overall.  Five trials have compared static 
mattresses or overlays with standard operating room mattresses with two trials demonstrating 
increased risk and two trials demonstrating decreased risk.[21-25]  Similarly, two trials have 
compared alternating support surfaces with static, usual care surfaces with no statistically 
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significant differences in pressure ulcer incidence, although results tended to favor alternating 
systems.[26, 27]  Additionally, a variety of repositioning regimens have been studied including 
changes in body position every two hours[28, 29], repositioning at a 30 degree tilt[30], 
alternating semi-Fowler position (30 degree elevation of the head and feet) and a lateral 
position[31], and repositioning based on nurse clinical judgment.[32]  Results were variable with 
only two trials demonstrating statistically significant reductions in risk with the initiation of 
repositioning protocols.[28, 30]  All trials were hampered by methodological shortcomings 
including inadequate descriptions of randomization or allocation concealment methods and lack 
of blinding of outcome assessors. 
Strategies for nutritional support include the supplementation of high-calorie oral liquid 
nutritional supplements[33-36] or supplementation of high fat, low-carbohydrate enteral 
formulas via tube feeding[37, 38].  Five of the six trials investigating nutritional supplementation 
found no difference between nutritional supplementation compared with standard hospital diet in 
risk of developing pressure ulcers.  A single trial of 672 patients found that high-calorie oral 
liquid nutritional supplementation in addition to a standard hospital diet was associated with a 
slightly lower risk of pressure ulcers at 15 days compared with standard hospital diet alone in 
elderly patients during the acute phase of a critical illness.[33]  
Finally, the category of preventative skin care products includes the application of 
creams, lotions, cleansers, dressings, and pads.  Studies of topical creams, lotions, and cleansers 
have primarily focused on commercially available products.  Studies of a hyperoxygenated fatty 
acid cream (Mepentol)[39] and Conotrane cream (benzalkonium chloride [an antiseptic] plus 
dimeticone [a silicone fluid which repels water])[40] demonstrated decreased risk of pressure 
ulcer development.  Moreover, a trial found use of Clinisan cleanser associated with a lower risk 
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of ulcer development compared to standard soap and water in patients with incontinence.[41] In 
comparison, other commercial studies have not demonstrated the advantages associated with the 
addition of topical agents.[42, 43]  Three trials have evaluated dressings or pads for the 
prevention of pressure ulcers with only one trial demonstrating a statistically significant 
reduction in pressure ulcer incidence.[44, 45]
Despite the wide variety of clinically available products for pressure ulcer prevention, it 
is readily apparent that further research is required and that currently available products, despite 
representing the standard of care, are woefully inadequate at attenuating the risk of pressure ulcer 
development.  Further trials should employ a clearly delineated protocol for the use of 
preventative interventions based on validated risk-assessment scores.  More research is needed to 
understand the effectiveness of preventative interventions with adherence to stringent 
methodological standards including the appropriate use of blinding with clear descriptions of 
usual care.  
1.3 Management of Pressure Ulcers      
Given the previously delineated negative sequelae of pressure ulcers on health status, 
patient quality of life, and health care costs, treatments that promote healing, shorten healing 
time, and minimize the risk of complications are urgently needed.  Pressure ulcer management, 
like pressure ulcer prevention, requires a variety of different treatment modalities, including 
interventions to treat the conditions that give rise to pressure ulcers, interventions to protect and 
promote healing of the ulcer, and surgical repair of the ulcer.[46, 47]  Most ulcers are treated 
using a combination of these approaches.  The standard of care for pressure ulcer treatment is 
typically guided by clinical practice guidelines, such as those developed by NPUAP, but are also 
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informed by patient-related factors such as comorbidities and nutritional status, local practice 
patterns, and the stage and features of the wound.[48]  
Support surfaces and nutritional supplementation are unique in the management of 
pressure ulcers as they represent interventions that address the underlying conditions that give 
rise to pressure ulcers.  As such, these strategies are utilized in both preventative and therapeutic 
interventions.  Examples of support surfaces include low-air-loss, alternating pressure, or air 
fluidized systems.  Air fluidized beds are made up of a lining mattress filled with small beads; air 
is forced through to create a fluid-like surface that redistributes pressure.  Five studies have 
compared air fluidized beds to other support surfaces and have consistently reported a positive 
effect compared to alternatives in promoting the reduction in size of pressure ulcers.[49-53]  
Alternating pressure systems have cells or sections that inflate and deflate to change the 
distribution of pressure.  When compared against air, fluid, or standard beds, alternating pressure 
beds have generally yielded similar results.[54-56]  Low-air-loss systems use power to provide a 
flow of air that helps regulate heat and humidity and may also adjust pressure.  Studies 
comparing low-air-loss beds to foam surfaces showed similar wound improvement.[57-59]  
Signs of poor nutrition, such as low levels of prealbumin, vitamin C, or zinc, are all 
associated with an increased incidence of pressure ulcers.[60, 61]  Studies have identified that 
when used in addition to other measures for treating pressure ulcers, protein-containing 
nutritional supplementation results in wound improvement.[62-65]  Two trials have examined 
the effect of micronutrient supplementation with either zinc sulfate or vitamin C with insufficient 
evidence for either intervention.[63, 66]  As such, guidelines formulated by international experts, 
including the National Pressure Ulcer Advisory Panel and the European Pressure Ulcer Advisory 
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Panel, include recommendations for providing high-protein, mixed nutritional supplementation 
to all patients at risk for pressure ulcer development.[48]
Non-surgical interventions targeted at protecting and promoting ulcer healing include 
wound dressings, topical applications, and various adjunctive therapies, such as negative 
pressure wound therapy and hyperbaric oxygen therapy.  
Wound dressings represent a 
cornerstone of pressure ulcer treatment and serve multiple functions, including padding and 
protection of the ulcer from pressure and friction, the provision of a moist wound environment 
and protection against dessication, serving as a barrier in patients with incontinence or other 
sources of wound contamination, wound exudate absorption, and promoting autolytic 
debridement of necrotic tissue and slough.  Studies have demonstrated that wound improvement 
is superior with hydrocolloid and foam dressings compared to gauze dressings.[67-73]  Current 
evidence is insufficient to advocate the use of hydrogels, transparent films, silicone, and alginate 
dressings.[72, 74-78]  Topical ointments and other therapies such as fibrinolytic enzymes and 
antimicrobial agents are also used in pressure ulcer management to provide moisture, promote 
tissue debridement, and eliminate or prevent infection.  Evidence regarding the effectiveness of 
collagenase and other debriding enzymes is currently inconclusive [79-81], while several studies 
have shown superior results compared to placebo with the application of platelet-derived growth 
factor in Stage III and IV pressure ulcers. [82-85]  Although topical antimicrobials are 
commonly used in pressure ulcer treatment, few studies have compared antimicrobials to 
placebos or other interventions and current evidence is insufficient to draw any conclusions 
regarding their effectiveness.[86, 87] 
Finally, for chronic pressure ulcers that have progressed to an advanced stage and are 
unable to reliably heal with conservative measures, surgical debridement and vascularized soft 
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tissue reconstruction may serve to provide definitive closure.  Surgical interventions range from 
local debridement of necrotic and nonviable tissue in the wound bed to direct closure, skin 
grafting, and closure with soft tissue flaps using either skin (cutaneous), fascia (fasciocutaneous), 
or muscle (myocutaneous) from unaffected parts of the body.  Techniques for wound closure 
depend on the location, size, and depth of the pressure ulcer as well as the specific nature of the 
patient’s medical comorbidities and previous surgical interventions.[88]  Primary closure is 
typically contraindicated due to the high risk of failure from increased tension at the closure 
site.[89]  Similarly, skin grafting is generally reserved for shallow nonhealing ulcers with a well-
vascularized wound bed and is rarely used due to the high risk of failure from mechanical 
shear.[89]  Current evidence is insufficient to determine if one approach to flap-based closure is 
superior to another due to overall poor study quality, study population heterogeneity, and 
differences in surgical technique.[90-95]  In the face of a limited evidence base, surgeons 
typically resort to general reconstructive surgical principles and prior experience to guide flap 
selection.  Fasciocutaneous flaps represent durable, well-vascularized flaps that spare the patient 
significant functional deformity and may provide good bony prominence coverage, but their 
limited bulk may prove insufficient for large or deep wounds.[88]  
Conversely, 
musculocutaneous flaps provide more depth of coverage at the cost of functional deformity, but 
are typically preferred in infected wounds due to the benefits imparted by a superior local blood 
supply including improved tissue oxygenation, antibiotic delivery, and enhanced lymphocytic 
function.[88]  The relatively recent development of perforator-based flaps have gained popularity 
since their introduction by Koshima and colleagues in 1993.[96]  Advantages of a perforator-
based flap includes preservation of the blood supply and muscles for possible future 
reconstructions.[97]  Despite the advantages associated with each reconstructive modality, 
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significant debate surrounds the selection of the optimal regional flap for the repair of pressure 
ulcers.[98-101]  Moreover, predictors for the ultimate success of flap reconstruction are poorly 
delineated, but include bacterial inoculation[102, 103], ulcer location[94, 104], nutritional 
status[105], postoperative pressure relief[105, 106], length of hospital stay,[104] spinal cord 
injury[104], and presence of joint contractures.[105]  
The predictive effect of bacterial 
inoculation requires special attention. Previous investigations have demonstrated up to 100-fold 
increases in bacterial count in inoculated wounds subjected to pressure and have established a 
threshold of 105 organisms per gram of tissue as a significant predictor of flap failure.[102, 103, 
107, 108]  Despite these findings, the current evidence base is woefully inadequate due to the 
preponderance of case series and experimental animal models, necessitating the development of 
a well-powered clinical study of the bacterial microbiome in inoculated pressure ulcers to 
develop mechanistic and predictive models for flap failure.  Recidivism rates due to pressure 
ulcer recurrence or flap failure is currently unacceptably high with overall rates as high as 39 
percent.[109]  These rates are even higher in spinal cord injured patients with a recurrence rate of 
70 percent in one study.[95]  Given these high rates of recurrence and the significant financial 
burden on the health care system associated with pressure ulcers, emphasis must be placed on the 
proper selection of patients for surgical reconstruction and the need to develop improved 
prevention strategies. 
Current treatment strategies for pressure ulcers are guided by product availability, local 
practice patterns, anecdotal evidence, and individualized decision making based on specific 
patient and wound factors.  Although there is general agreement on the standards of care with 
respect to the types of treatment employed, evidence comparing interventions within a given 
intervention strategy are sparse, limiting the ability for clinicians to judiciously select the optimal 
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interventions for their patients.  Therefore, further studies should focus upon the comparative 
effectiveness of different management approaches. 
1.4 Description of Study Products
Patients presenting for operative management of stage III or IV pressure ulcers will be 
assessed for study inclusion using study inclusion and exclusion criteria.  Consenting subjects 
will be randomized to receive therapy with either the treatment support surface (Dolphin Fluid 
Immersion Simulation® System) or the control support surface (Clinitron® Rite Hite® Air 
Fluidized Bed).  
The Dolphin Fluid Immersion Simulation® system represents a novel technology that 
was initially developed by the U.S. Navy in response to the need to transport specially trained 
marine mammals over long distances outside of water.  The system was designed in order to 
minimize the harsh vertical shear forces of gravity, which ultimately cause internal organ trauma 
and circulatory distress.  The Dolphin Fluid Immersion Simulation® system leverages an 
advanced 3D immersion technology in order to automatically simulate a fluid environment, thus 
maintaining near normal blood flow and optimizing tissue oxygenation.  The system is fully 
autonomous with monitoring of the support surface over 100 times per second, facilitating 
constant adjustments based on patient repositioning.  A recent study by Kohanzadeh et al. at the 
University of California San Diego has demonstrated statistically significant improvements in 
tissue blood flow compared to standard bed and gurney systems with 87% retention of perfusion 
on the Dolphin Fluid Immersion System® mattress vs. 16% on standard mattresses.[110]  
Moreover, Sparrow Specialty Hospital, a 36-bed long term acute care hospital, replaced a 6 week 
post myocutaneous flap protocol with an air-fluidized bed system with a 6 week protocol using 
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the Dolphin Fluid Immersion Simulation® system based protocol.  After intervention, patients 
achieved equivalent flap outcomes with a $26,249 reduction in costs over the study time 
period.[111] 
Like other air-fluidized systems, the Clinitron® Rite Hite® air fluidized therapy bed is 
made up of small beads with air forced through to create a fluid-like surface that redistributes 
pressure.  Three randomized clinical trials, have specifically examined the Clinitron® system to 
alternatives.  A study by Allman et al. comparing an air-fluidized system to an alternating 
pressure system showed a statistically significant decrease in total wound surface area and pain 
with a 5.6 relative odds of improvement compared to the alternating pressure system over the 
median 13 day follow-up period.[50]  Furthermore, Monro and investigators compared 20 
Dolphin Fluid Immersion Simulation® System
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patients on air-fluidized beds to 20 people on standard hospital beds with mean ulcer area 
declining on the air-fluidized bed and increased on standardized beds over the course of each 
patient’s hospital stay.[53]  Finally, Jackson et al. compared 15 patients on an air-fluidized 
system to 20 individuals on several different standard care support surfaces with statistically 
significant reductions in wound area.[51] 
Potential benefits touted by the Dolphin Fluid Immersion Simulation® System include a 
completely automated autonomic system with minimal required training as the system requires 
no programming or manual data input.  This is in contrast to the Clinitron® Rite Hite® Air 
Fluidized Therapy Bed, which requires various adjustments by health care staff.  The Dolphin 
Fluid Immersion Simulation® System fits into existing bed frames permitting potential 
Clinitron® Rite Hite® Air Fluidized Therapy Bed
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integration across the clinical care continuum and reducing the threshold for adoption of the 
therapeutic support surface.  Current fluidization technologies are affected by environmental 
factors such as room temperature and humidity, potentially requiring health care staff to employ 
a variety of strategies such as lowering the room temperature, closing windows, and readjusting 
blankets on the unit that may negatively impact patient comfort while compromising health care 
resource utilization.  In addition, patient transfers into and out of air-fluidized beds is technically 
difficult, requiring two providers, and may present an obstacle to care in the home environment 
where adequate staffing may not be available.  Although Joerns makes no claims to the ease of 
patient transfers in the technical specifications of the Dolphin Fluid Immersion Simulation®, the 
facilitation of patient transfers could significantly reduce staffing needs while facilitating care in 
an outpatient environment.  Finally, the previous study by Allman et al. demonstrated significant 
benefits with respect to wound healing and pain compared to conventional surfaces, even with a 
repositioning regimen of every 4 hours rather than every 2 hours in the conventional surface 
group.[50]  The Dolphin Fluid Immersion Simulation® System claims to require no need for 
caregiver or staff intervention due to the continuous monitoring of the patient’s weight, three-
dimensional surface area, and movements in order to effectively manage the distribution of the 
patient’s weight, potentially obviating the need for frequent repositioning regimens.
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1.5 Study Rationale 
Although valuable, previous clinical studies investigating the Dolphin Fluid Immersion 
Simulation® system have not adequately compared the system to other standard of care support 
surfaces.  Studies thus far have been limited to observational investigations of tissue perfusion 
and post-intervention investigations without an active comparator group.  Furthermore, previous 
trials comparing air-fluidized beds to other systems have been limited by relatively small sample 
sizes with inadequate analysis of outcomes that focused primarily on wound surface area and 
complete tissue closure.[50, 51, 53]  Thus, the proposed study is designed to examine the 
potential benefits of the Dolphin Fluid Immersion Simulation® system following operative 
closure of pressure ulcers compared to a representative air-fluidized system, the Clinitron® Rite 
Clinitron® Rite Hite® Air Fluidized Therapy Bed Input System
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Hite® air-fluidized therapy bed.  Currently, there is a paucity of data for clinicians to advocate 
for the usage of novel fluid immersion simulation systems compared to current standard of care 
support surfaces.  The effects of the Dolphin Fluid Immersion Simulation® system will be 
studied and compared to the Clinitron® Rite Hite® air-fluidized therapy bed in a controlled 
manner after surgical closure of subjects’ wounds.  
2. Study Objectives
The primary objective is to compare the effects of the Dolphin Fluid Immersion 
Simulation® System to an air-fluidized system after definitive operative closure of pressure 
ulcers.  This post-market, on-label study will evaluate the effectiveness of the Dolphin Fluid 
Immersion Simulation® System when compared to a standard of care support system.  
2.1. Endpoint Criteria Measurements
2.1.1. Primary Endpoint
1. Success of closure and incidence of wound related dehiscences or flap complications 
within the two weeks following surgical closure of the pressure ulcer. 
2.1.2. Secondary Endpoints
1. Bacterial speciation and antibiotic resistance taken just prior to and following the first 
surgical debridement and their subsequent relation to complications and time to 
closure in each group.  
2. Differences in bacterial speciation and antibiotic resistance, total bacterial counts, and 
pressure ulcer microbiome.  Bacterial speciation and antibiotic resistance will be 
determined by quantitative cultures and PCR analysis.  Differences in total bacterial 
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counts will be determined by quantitative PCR analysis.  Pressure ulcer microbiome 
will be assayed via PCR assays conducted by PathoGenius Laboratory™.  
Comparisons will be made between biopsies taken prior to and following the initial 
operative debridement, following any subsequent debridements, and prior to prior to 
operative closure.
3. Qualitative and quantitative markers of inflammation in the pressure ulcer utilizing 
protein and PCR assays.  Comparisons will be made between tissue biopsies taken 
prior to and following the initial operative debridement, following any subsequent 
debridements, and prior to operative closure.
4. Evaluation of patient characteristics (age, comorbidities, nutritional parameters, 
spasticity, medications, ulcer history) and their relation to early and late recurrences 
as well as complications.
5. Comparison of outcomes and complication rates based off of flap technique and 
surgeon guided descriptions of the operative closure. 
6. Total costs incurred including treatment costs, the costs of associated complications, 
cost of the hospital stay, and any other unforeseen costs during the two week study 
period following operative closure.
7. Differences in quantitative patient and nurse survey responses regarding acceptability 
and tolerance of each therapeutic modality, including pain management.
8. Regular follow-up via phone interviews to assess for additional complications and 
need for additional therapies or surgical procedures up to 1 year after surgical closure.
2.1.3. Safety Endpoints
1. Difference in number of Adverse Events
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3. Study Design
3.1. Overview
This protocol outlines a prospective, randomized, single-center, human subject trial 
comparing the Dolphin Fluid Immersion Simulation® system to a representative air-fluidized 
support system, the Clinitron® Rite Hite® air-fluidized therapy bed.  Following operative 
debridement, patients will be randomized to receive therapy with either the Dolphin Fluid 
Immersion Simulation® system (treatment) or the Clinitron® Rite Hite® air-fluidized therapy 
bed (control).  Subjects will receive assigned study therapy following definitive pressure ulcer 
closure and extending two weeks beyond closure, reflecting current standard practice for 
pressure ulcer management.  Investigators will follow, evaluate, and make clinical decisions 
regarding wound therapy, further debridement, or readiness for closure.  The primary endpoint 
will not be followed during this period.  Data regarding secondary endpoints other than the tissue 
biopsies delineated in Section 2.1.2 will also not be collected during this period.  All other 
therapies will otherwise represent the standard of care for pressure ulcer management as 
delineated by the joint National Pressure Ulcer Advisory Panel and European Pressure Ulcer 
Advisory Panel guidelines.[48]  The two week study period will begin following the definitive 
surgical procedure for pressure ulcer closure, at which time data regarding the primary endpoint 
and the secondary endpoints laid out in Section 2.1.2 will be collected.   
The determination of a wound’s appropriateness for definitive closure is currently viewed 
as a clinically subjective event.  Readiness for closure is established when the Investigator deems 
that the wound has been adequately debrided, cleaned, and a definitive procedure can be 
performed. 
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The treatment period for Dolphin Fluid Immersion Simulation® system Treatment 
therapy or Clinitron® Rite Hite® air-fluidized therapy bed Control therapy will begin following 
the closure visit and will continue until two weeks following the definitive operative procedure.  
Both support surfaces will only be used in the inpatient setting.  Subjects will remain 
hospitalized for at least two weeks following their definitive surgical procedure.  After two 
weeks of inpatient hospitalization, Control or Treatment therapy may be continued although the 
only endpoint that will continue to be measured will be the incidence of additional 
complications, need for additional surgeries, or need for other therapeutic interventions.   
Subjects will continue to be followed for one year after the two week study period in 
order to evaluate the incidence of complications and the need for additional therapeutic 
interventions.  Assessments will include monthly telephone interviews.  
An interim analysis of the Intent-to-Treat (ITT) population will be performed when 50 
subjects in each arm have satisfied the ITT criteria (see Section 7.4).  An Independent Data 
Monitoring Committee (IDMC) comprised of a biostatistician and clinicians will convene to 
review the data from the interim analysis and evaluate the assumptions for the original sample 
size calculation.  The IDMC will determine if the sample size will be adjusted based upon results 
from the interim analysis. 
3.2. Duration of Clinical Investigation Participation
Screening: -90 days through day 0 (Initial OR Visit)
Treatment period following randomization: Up to 60 days 
Treatment period evaluating primary endpoint: 14 days
Follow-up period: 365 (±20 days) after two week prior endpoint evaluation period
Total duration of participation per Subject: Up to 549 days
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Duration of Study Enrollment Period: Up to 18 months
Figure 1. Clinical Decision Study Flowchart
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4. Selection of Subjects
4.1. Recruitment and Screening
Patients who present to the investigator’s institution (through clinic admission, direct 
transfer from another facility, or through the emergency room) and are, or will be, admitted as an 
inpatient for operative management of a stage III or IV pressure ulcer may be recruited to 
participate in the study.  Additionally, direct marketing for subject recruitment will be performed 
by mailing letters to Dr. Robert Galiano’s Rehabilitation Institute of Chicago patients and via 
television, radio, and online advertisements.  
Patients approached for study participation will be at least 18 years of age and less than 
85 years of age at the time of consent, will undergo wound debridement surgery and subsequent 
operative closure, and will meet all eligibility requirements.  Those meeting eligibility criteria for 
the study will have the study explained to them by the Investigator.  An Informed Consent Form 
will be provided to sign according to section 5.1 prior to undergoing any study procedures.  
Patients will be encouraged to ask questions of the investigators.  It will be made clear to the 
patient that not participating in the study will in no way influence the treatment plan or the 
relationship with the physician.  
There is no cap on the number of subjects that can be screened.  Additional subjects will 
continue to be recruited as needed to reach the minimum number of 100 treated per protocol, per 
arm.  
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4.1.1. Subject Stipend 
No reimbursement or compensation will be provided for participation in this study.  Costs related 
to the treatment and control arms, including the support surfaces and staff training, will be 
covered by the Sponsor. 
4.1.2. Wound Selection
Potential subjects who consent to study participation will be assigned a unique screening 
number.  Only one wound per subject will be included in the study.  Subjects with multiple 
wounds will have each wound measured for volume.  The wound with the largest volume 
meeting all pre-operative eligibility requirements will be chosen for inclusion in the study.  The 
location of the wound, and if it is a new or recurring wound, will be documented.  Only stage III 
or IV pressure ulcers will be eligible for inclusion in this study.  
At the conclusion of the initial surgical debridement, if all inclusion and no exclusion 
criteria continue to be met, the subject will be randomized into a study group and assigned a 
unique Randomization number.  If the subject does not continue to meet all inclusion and no 
exclusion criteria at the end of surgical debridement, they will not be randomized and will be 
documented as a screen failure.  The reason for exclusion will be noted on the Screening Log.  
At the time of surgical closure, if all inclusion and exclusion criteria continue to be met, 
the Randomization number will become a unique Subject ID number.  If the subject does not 
continue to meet all inclusion and no exclusion criteria number prior to and up to the point of 
operative closure, they will be documented as a randomization failure.  The reason for exclusion 
will be noted on the Randomization log.  
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4.2. Inclusion Criteria
The Subject:
1. will be admitted as an inpatient
2. is ≥ 18 years of age and ≤ 85 years of age at time of consent
3. is able to provide his/her own informed consent
4. is deemed by the investigators to be reasonably compliant
5. has a pressure ulcer meeting criteria for stage III or IV
6. has not participated in a clinical trial within the past 30 days
7. has a 30 day wound history available if the wound has been previously treated
4.3. Exclusion Criteria
The Subject:
1. has a life expectancy of < 12 months
2. is not healthy enough to undergo surgery for any reason
3. has a history of radiation therapy
4. is, in the opinion of the investigator, noncompliant 
5. has a history of > 3 closures of pressure ulcers in the same site
6. has a history of a bleeding disorder
7. has severe fecal incontinence
5. Study Procedures and Treatment
5.1. Informed Consent
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The Investigator will discuss the purpose of this clinical investigation with potential 
subjects.  Each potential subject will review the IRB approved Informed Consent Form (ICF).  
The subject and the Investigator (or designated medically licensed sub-investigator), must sign 
and date the ICF before the subject can undergo any clinical investigation-related procedures.  
The subject’s informed consent will be obtained under these conditions:

Subjects must be made aware of the purpose of the clinical investigation and the potential 
risks and benefits known or that can be reasonably predicted or expected

Subjects must be given the opportunity to ask the Investigator questions and must be 
provided time to consider participation in the clinical investigation

ICFs will be written in language that is non-technical and understandable to the subject 

Subjects will not be led to believe that they are waiving their legal rights to release the 
Investigator, Joerns®, Clinitron®, the Institution, or any of their agents from liability or 
negligence

Subjects will be asked to sign and date the ICF indicating their informed consent to be 
enrolled in the clinical investigation

The Investigator’s responsibilities during the ICF process include:
a.
Screening out potential subjects who may not be able or willing to comply with 
the clinical investigation protocol
b. Ensuring that subjects have signed the ICF prior to undergoing any clinical 
investigation related procedure
c.
Ensuring that subjects are provided a copy of the signed ICF
5.2. Screening
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Patients who are scheduled for hospital admission or are already admitted with a pressure 
ulcer or multiple pressure ulcers will be identified, consented, and screened for the study 
according to Section 4.  Potential subjects presenting with multiple pressure ulcers requiring 
debridement will have each wound assessed pre-operatively.  The largest pressure ulcer meeting 
eligibility requirements listed in Section 4 will be screened for inclusion in the study.  For 
subjects with multiple pressure ulcers, any pressure ulcers not selected as the study wound will 
not be followed but will otherwise receive institutional standard wound care at the direction of 
the treating clinician. 
Upon signing the ICF, subjects will be assigned a unique Screening Number.  The 
Screening number will start at 001 and increase sequentially with each subject screened.  
Screened subjects will be entered onto a screening log.  Once a number is assigned it cannot be 
re-assigned to another subject.  In the instance a subject is considered a screen failure, they will 
keep the screening number assigned to them and the screen failure log will be completed noting 
the reason(s) for screen failure.  
Screened subjects consenting to participate in the study will not have screening 
laboratory tests collected. However, prior laboratory testing results will be documented, 
including WBC with differential, HgbA1c, glucose, BUN, Creatinine, Total Protein, Albumin, 
and Pre-Albumin.  A focused medical and surgical history, physical exam, and wound history 
will be conducted and recorded.  The subject’s current medications will be documented. 
5.3. Randomization
Subjects will be taken to the operating room for the initial debridement procedure of their 
wound.  At the end of the procedure, Subjects who continue to meet all inclusion and no 
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exclusion criteria will be randomized in a 1:1 ration to be treated with either the Dolphin Fluid 
Immersion Simulation® System or the Clinitron® Rite Hite® Air-fluidized bed.  Since there 
may be differences in pressure ulcer types, a stratified randomization will be used for this study 
to prevent imbalance between treatment arms.  Permuted blocks will be used to achieve equal 
number of Subjects assigned to the Dolphin Fluid Immersion Simulation® System or the 
Clinitron® Rite Hite® Air-fluidized bed to generate a randomization schedule including Subject 
numbers and treatment assignments.  Envelopes will be prepared corresponding to each row in 
the randomization schedule and each Subject number and treatment group will be printed on 
labels.  
Prior to study initiation, sealed pre-numbered randomization envelopes will be provided 
to the research staff and will be used to obtain a randomization assignment.  Opening of the 
randomization envelope will occur intra-operatively at the conclusion of the initial surgical 
debridement of the wound and confirmation that all inclusion and no exclusion criteria were 
encountered.  Study staff will use the Randomization Number labels contained in the envelope.  
This number will become the Subject ID for patients who undergo operative closure.  The 
assignment will be:

Subject is randomized to Dolphin Fluid Immersion Simulation® System (Treatment arm)

Subject is randomized to Clinitron® Rite Hite®Air-fluidized bed (Control arm)
The research staff will note treatment assignments and instruct the investigator.  Control or 
Treatment therapy support surfaces will be initiated following operative closure, according to the 
manufacturer’s recommendations. 
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In order to ensure consistent study treatment, subjects will receive assigned Control or 
Treatment therapy within their study arm after  the wound is deemed ready for closure or 
coverage by the Investigator.  
Support surface therapy crossover prior to and during the study treatment period is not 
permitted.  Subjects randomized to the Dolphin Fluid Immersion Simulation® System Treatment 
arm are the only subjects that will receive this therapy at any time during the study period.  If 
Dolphin Fluid Immersion Simulation® System is discontinued, subjects in the treatment arm will 
transition to an institutional standardized support surface.  Subjects randomized to the Clinitron® 
Rite Hite® Air-fluidized bed will receive only this therapy prior to and during the study 
treatment period.  
If the assigned Control or Treatment therapy must be discontinued prior to deeming the 
wound ready for closure or coverage, subjects will transition to a standard institutional support 
surface.  These subjects will remain in the study and continue to be followed but will not be 
included in the per protocol analysis group.  
5.4. Initial OR Debridement of Wound
Prior to start of the initial debridement procedure in the operating room, the wound will 
be assessed and the results documented.  A pre-debridement digital photograph of the wound 
will be taken.  Prior to the surgical prep, a pre-debridement wound swab will be obtained for 
aerobic and anaerobic culture and a pre-debridement wound scraping will be obtained for PCR 
and protein analysis. 
The wound will then be debrided.  At the conclusion of the debridement, the wound will 
be irrigated with at 5L of normal saline unless contraindicated in the judgment of the 
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Investigator.  Antibiotic solutions are permitted for irrigation based on the judgment of the 
Investigator and standard of care practices. 
If the wound is determined to be ready for immediate closure, the closure procedure can 
be performed.  Closure at the time of the initial surgical debridement will be considered as the 
initiation of the study period.  
If all inclusion criteria and no exclusion criteria are met at the end of the surgical 
procedure, the subject will be randomized according to Section 5.2.  After randomization, a post-
debridement wound assessment will be performed and documented.  A post-debridement digital 
photograph of the wound will be taken.  A post-debridement wound swab will be obtained for 
aerobic and anaerobic culture and a post-debridement wound scraping will be obtained for PCR 
analysis.  
5.5. Wound Care Prior to Closure
During the subject’s hospital admission, interventions other than the support surface 
utilized will be based on institutional standard of care practices.  These include wound dressings, 
topical applications, and the use of adjunctive therapies such as vacuum-assisted closure and 
hyperbaric oxygen therapy.  The type of dressing used will be documented.  
5.6. Additional OR Wound Debridement 
The Investigator will determine if additional surgical debridement is required after the 
Initial OR Visit. This decision is typically based on ulcer appearance and periodic post-
debridement culture results. To ensure consistent treatment, subjects returning to the operating 
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room for additional debridement of their wound should resume their assigned study therapy after 
the procedure unless contraindicated in the judgment of the Investigator. 
Prior to the start of the debridement procedure, the wound will be assessed and the results 
documented.  The wound will be debrided according to the discretion of the Investigator.  At the 
conclusion of the debridement the wound will be irrigated with at 5L of normal saline unless 
contraindicated.  After wound irrigation, a post-debridement assessment will be performed and 
documented.  Wound swabs will be taken both prior to and following all additional debridement 
procedures. Tissue scrapings will be taken following all additional debridement procedures.
5.7. Wound Closure or Coverage 
When the Investigator determines that the wound is ready for closure or coverage, the 
study period will be initiated.  A wound swab will be obtained for aerobic and anaerobic culture 
and a wound scraping will be obtained for PCR and protein analysis, a wound assessment will be 
performed, and the date of closure determination will be documented.    
Definitive wound 
closure for this study is defined as complete approximation of the wound edges, complete 
coverage of the wound via tissue transfer or skin graft, or any combination of these definitive 
techniques that results in complete elimination of the wound bed.  Debridement may be 
performed prior to surgical closure or coverage.  All operative procedures including any 
debridement must be documented.  The use of a cutaneous, fasciocutaneous, myocutaneous, or 
perforator-based flap will be documented.  The amount of tension and the potential dead space 
remaining following closure will be documented by the surgeon performing the procedure.  The 
adequacy of these assessments will be assessed by a blinded surgeon reviewer.  If a flap fails 
during the immediate postoperative period, the subject will be removed from the study and 
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transitioned to a standard institutional support surface.  These studies will continue to be 
followed, but will not be included in the per protocol analysis group. 
5.8. Two Week Study Period
Subjects will be followed for two weeks following primary closure for the primary 
endpoint of wound dehiscences and flap complications.  Data regarding cost of hospital stay will 
also be compiled during the two week study period.  Nurses caring for patients during this time 
period will receive surveys in order to assess the ease of use and acceptability of the Control or 
Treatment Arms.  Patients will receive a survey after one week and two weeks in order to 
evaluate their comfort and acceptability of the Control or Treatment Therapies.  
5.9. Follow-Up After Two Week Study Period
Subjects may be discharged from inpatient care when deemed appropriate by the 
Investigator following the two week study period.  Monthly phone interviews will be conducted 
in order to assess for additional wound complications or necessary therapies related to the wound 
studied.  
6. Study Assessments/Measurement Tools
6.1. Quantitative PCR Analysis
Specimens will be collected through tissue scrapings of the wound bed before and after 
the initial debridement, after each additional debridement and when the wound is deemed ready 
for closure.  The samples will be analyzed for bacterial speciation and quantification through 
PCR techniques.  Samples will be sent to the PathoGenius Laboratory® for measurements of the 
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tissue microbiome.  Additionally, PCR assays for inflammatory markers will be conducted on 
the samples by the Principal Investigator’s lab.  
6.2. Qualitative Aerobic and Anaerobic Cultures
Culture specimens will be collected through swab cultures at the deepest point in the 
wound before and after the initial debridement, before and after each additional debridement, and 
when the wound is deemed ready for closure, according to current techniques.  Culture swabs 
will be placed in an appropriate transport media and sent to the institutional laboratory for 
qualitative aerobic and anerobic analysis.  Due to the turn-around-time of qPCR results, only the 
qualitative aerobic and anaerobic culture results will be used as the indicator of wound infection 
post debridement for the purposes of guiding treatment.  
6.3. Quantitative Protein Analysis
Specimens will be collected through tissue scrapings of the wound bed before and after 
the initial debridement, after each additional debridement, when the wound is deemed ready for 
closure, and two weeks following closure.  Protein-based assays of inflammatory markers will be 
conducted on the samples.
6.4. Laboratory Tests
Laboratory testing will not be performed for the study. If available, results of the 
following laboratory tests will be collected from the subject’s medical history and/or from 
standard of care testing that is required per institutional standards.  The Investigator will 
determine if abnormal test results are clinically significant.  All clinically significant laboratory 
results will be recorded as AEs.
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1. White Blood Cell Count with differential (CBC with differential)
a.
Pre-operatively, if available
b. When wound is deemed ready for closure, if available
c.
Following two week study period, if available
2. HbA1c
a.
Pre-operatively, if available
3. Prealbumin/Albumin/Total Protein
a.
Preoperatively, if available
4. Glucose
a.
Pre-operatively, if available
5. BUN/Creatinine
a.
Pre-operatively, if available
6. C Reactive Protein
a.
Pre-operatively, if available
7. Erythrocyte Sedimentation Rate
a.
Pre-operatively, if available
8. Transferrin
a.
Pre-operatively, if available
9. Alkaline Phosphatase
a.
Pre-operatively, if available
10.  Glomerular Filtration Rate
a.
Pre-operatively, if available
11.  Aspartate Aminotransferase Test
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a.
Pre-operatively, if available
12.  Alanine Aminotransferase Test
a.
Pre-operatively, if available
6.5. Clinical Wound Assessments
Wound assessments are performed by the Investigator in order to capture key features of 
study wounds.  Wounds will be measured to determine the volume.  Wound volume will be 
recorded in cubic centimeters by standardized measurement of length, width, and depth using a 
ruler.  Wound length will be measured along the surface of the body in the longest dimension of 
the wound.  Width will be determined from the widest point of the wound that is perpendicular to 
the length in the same plane of measurement.  Depth will be measured from the surface of the 
skin to the deepest part of the wound bed perpendicular to the plane of measurement for the 
length and width.  
Wound characteristics and appearance will be recorded using the following scale:
Wound Depth
1 = Blanchable erythema on intact skin
2 = Partial thickness skin loss involving 
epidermis and/or dermis
3 = Full thickness skin loss involving damage 
or necrosis of subcutaneous tissue; may extend 
down to but not through underlying fascia; and 
or mixed partial and full thickness and or tissue 
layers obscured by granulation tissue
4 = Obscured by necrosis
5 = Full thickness skin loss with extensive 
destruction, tissue necrosis, or damage to 
muscle, bone, or supporting structures
6.6. Concomitant Medications and Antibiotic Use
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This protocol does not specifically prohibit any concomitant medications.  The study will 
collect and document the frequency, dose, indication, and classification of all antibiotic 
medications.
Antibiotic use will be at the discretion of the Investigator.  Antibiotic name, category, 
dose, frequency, and duration for therapy must be documented. Rationale for antibiotic therapy 
must be documented including whether the antibiotic therapy is prophylactic, empiric, or culture 
directed and its relationship to the wound.
6.7. Wound History
The Subject’s wound will be assessed at screening and a wound history will be captured.  
The history will include prior wound related surgeries and treatments including but not limited to 
hyperbaric therapy, use of biologics, debridements, closure, revascularization procedures, prior 
infection, previous use of negative pressure wound therapy, advanced moist wound therapy, 
which have occurred within the past 30 days.  The history will also document onset and 
chronicity of the wound and anatomic location.  
For Subjects who present with multiple wounds, all wounds will be assessed at screening.  
The wound with greatest volume will be selected for the study and a wound history will be 
recorded. 
6.8. Operative Documentation
1.
Pre-operative wound assessment and measurement of volume
2.
Procedure Type:
a.
Debridement
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b.
Closure ( type of closure—flap, autologous skin graft, delayed primary)
I.
Type of Flap
i.
Cutaneous
ii.
Fasciocutaneous
iii.
Myocutaneous
iv.
Perforator-Based
c.
Other (non-debridement, non-closure procedure)
d.
Irrigation solution and volume used
3.
Wound related operative complications
4.
Post-operative wound assessment and measurement of volume (if applicable)
5.
Treatment or control support surface
6.
Surgeon guided description of operative closure will be evaluated using the following 
scale:
Tension
1 = No Tension
2 = Minimal Tension
3 = Moderate Tension
4 = High Tension
5 = Extremely high tension
Potential Dead Space Assessment
1 = No Dead Space
2 = Minimal Amount of Dead Space
3 = Moderate Amount of Dead Space
4 = High Amount of Dead Space
5 = Extremely High Amount of Dead Space
 6.9. Digital Wound Photographs
Standard digital photographs will be captured for each study wound. Two dimensional 
wound images will be captured using a standard digital camera.  
Digital photos will be taken of the wound for all subjects at the following times:
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
Initial OR Debridement (pre- and post-debridement)

Additional OR wound debridements (pre- and post-debridement)

Surgical Closure (pre- and post-closure)

Following two week study period
6.10. Clinical Acceptance of Treatment Arms
Nurses and patients will be asked to complete a quantitative survey evaluating ease of 
use, acceptability, and patient comfort.  Nurses using each system will be asked to complete a 
survey at one week of treatment and following the trial.  Patients will be asked to complete a 
survey at one week of treatment and following the end of the study period.  
Nurse acceptability will be evaluated using the following scale: 
Ease of Use
1 = No difficulty
2 = Minimal difficulty
3 = Moderate difficulty
4 = High difficulty
5 = Extreme difficulty
Amount of Training Required
1 = No training
2 = Minimal training
3 = Some training
4 = High amount of training
5 = Very high amount of training
Time Required for Troubleshooting or 
Otherwise Occupied by Device
1 = No time
2 = < 5 minutes a day
3 = 5 to 10 minutes a day
4 = 10 to 30 minutes a day 
5 = > 30 minutes a day
Patient acceptability will be evaluated using the following scale:
Comfort
1 = Very comfortable
2 = Comfortable
3 = Neither comfortable or uncomfortable
4 = Uncomfortable
5 = Very uncomfortable
Difficulty with Mobilization
1 = No difficulty
2 = Minimal difficulty
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3 = Moderate difficulty
4 = High difficulty
5 = Extreme difficulty
Pain at Surgical Site
1 = No pain
2 = Minimal pain
3 = Moderate Pain
4 = High pain
5 = Extreme pain
7. Statistical Design
The primary objective is to measure and compare the effects of the Dolphin Fluid 
Immersion Simulation® System to air-fluidized beds in pressure ulcers undergoing operative 
closure.  
Clinical outcomes of interest for this study are defined as the incidence of wound related 
dehiscences or flap complications within the two weeks following surgical closure of the 
pressure ulcer; the number of operating room debridements required after initial debridement to 
when the wound is deemed appropriate for closure or coverage; the difference in bacterial count 
from the time of the initial debridement to subsequent debridements and the time of operative 
closure; costs incurred during the two week period following surgical closure; and nurse and 
patient acceptability of the Treatment and Control arms. These outcomes will be analyzed and 
compared between the Dolphin Fluid Immersion Simulation® System and the Clinitron® Rite 
Hite® Air-fluidized bed. 
7.1. Statistical Methods Planned
Unless specified otherwise, SPSS® Version 22 or higher will be utilized to perform the 
statistical analyses of efficacy and safety measures.  
Categorical variables will be summarized in general using frequencies and percentages, 
whereas continuous variables will be summarized in general using descriptive statistics of 
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number of observations (n), mean, standard deviation (SD), minimum (Min), median, and 
maximum (Max).  
Hypothesis testing, unless otherwise indicated, will be performed at the 5% significance 
level.  All p-values will be rounded to four decimal places; p-values less than 0.0001 will be 
presented as ‘<0.0001’ in all tables.  All group comparisons from analysis of variance (ANOVA) 
and/or analysis of covariance (ANCOVA) models will be based on Type III sums of squares.  
All confidence intervals will be two-sided with 95% coverage. 
7.2. Determination of Sample Size
An adaptive design will be employed to monitor the study to determine the target number 
of subjects required to achieve significance at the alpha = 0.05 level. 
A previous systematic review of complications following flap based surgery for pressure 
ulcers demonstrated a mean complication rate of 19.6% with a standard deviation of 
approximately 3% following the usage of perforator based flaps.[106]  We have determined that 
a difference in proportion of responders of at least 10% would be regarded as clinically 
meaningful. 
Assuming a 10% delta in proportion between support surfaces and a “confirmed” 
complication rate of approximately 20% with a standard deviation of 5%, a sample size of 98 per 
group will provide a statistical power of 80% at the significance level of 0.05 (2-sided).  
Therefore, a total of 200 subjects randomized with an equal allocation ratio (1:1) of the 
Treatment arm versus Control arm will be needed in the present study.  
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7.3. Interim Analysis
The study data will be evaluated when approximately 50 subjects in each treatment arm 
have completed the study.  Data from the interim analysis will be used to verify the assumptions 
for sample size calculation or to re-estimate the sample size as well as to confirm the safety of 
the study.  The interim analysis will be based off of the available data for the ITT population. 
To ensure data integrity and unbiased clinical decisions, the planned interim analysis will 
be conducted under the auspices of the Independent Data Management Committee (IDMC) 
assigned to this study.  The IDMC will disseminate interim results in a manner that will protect 
the scientific and ethical aspects of the study.  The IDMC will review the study data at interim 
analysis to re-estimate the final target sample size using 80% power for the primary endpoint of 
number of wound dehiscences or flap complications following operative closure using the 
approach described by Chen et al.[112] 
7.4. Analysis Populations
The following Subject populations will be considered for this clinical study:

Per-Protocol Population (PP): All subjects who are randomized and received either 
Control or Treatment therapy for two weeks after wound closure, completed the 
protocol’s required evaluations, and did not have any major protocol deviations.  The 
primary and secondary effectiveness analyses for this study will be based on this 
population.

Intention-to-Treat (ITT): All subjects who are randomized and received either Control or 
Treatment therapy regardless of its duration, and without a major medical event after 
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enrollment unrelated to the study treatment that significantly alters the treatment course 
or would affect the subject’s ability to participate in the study. 

Safety Population: The Safety population will consist of all subjects who are randomized 
and treated with the Control or Treatment therapy regardless of its duration.  All safety 
results will be presented based on the Safety Population
7.4. Efficacy Analyses
7.4.1. Primary Efficacy (Number of successful closures and wound related dehiscences or flap 
complications)
The primary effectiveness endpoint for this study is the number of successful closures 
and the total number of wound related dehiscences or flap complications during the two weeks 
following operative closure.  The number of debridements as defined above will be calculated 
and displayed by treatment group and overall and then will be modeled using a two-sample t-test.  
The null and alternative hypotheses are below. 
H0: The Dolphin Fluid Immersion Simulation® System and Air-fluidized treatment groups have 
equal closure rates and numbers of wound related dehiscences and flap complications during the 
two weeks following operative closure.
H1: The Dolphin Fluid Immersion Simulation® System and Air-fluidized treatment groups have 
unequal closure rates or different numbers of wound related dehiscences and flap complications 
during the two weeks following operative closure.
7.4.2. Secondary Efficacy
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7.4.2.1 The difference in bacterial speciation and antibiotic resistance taken just prior to and 
following the first surgical debridement and their subsequent relation to complications and time 
to closure in each group.  The differences will be calculated and displayed by treatment group 
and bacterial speciation and will be compared using an ANOVA analysis.  
The null and alternative hypotheses are below.
H0: Bacterial speciation, antibiotic resistance, and treatment surface have no relation to the 
overall incidence of complications or time to operative closure.
H1: Bacterial speciation, antibiotic resistance, and treatment surface are related to the overall 
incidence of complications or time to operative closure.
7.4.2.2 The difference in total bacterial counts as determined by quantitative PCR analysis after 
the initial operative debridement, following initial debridement, following subsequent 
debridements, and prior to operative closure.
The differences will be calculated and displayed by treatment group and overall and then will be 
compared using a two-sample t-test.  
The null and alternative hypotheses are below.
H0: The Dolphin Fluid Immersion Simulation® System and Air-fluidized treatment groups have 
equal differences in total bacterial counts.
H1: The Dolphin Fluid Immersion Simulation® System and Air-fluidized treatment groups have 
unequal differences in total bacterial counts.
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7.4.2.3 Differences in pressure ulcer microbiome measured by quantitative PCR assays 
conducted by PathoGenius Laboratory™ just prior to and following initial debridement, 
following subsequent debridements, and prior to operative closure.
Differences will be calculated and displayed by treatment group and overall and then will be 
compared using a two-sample t-test.  
The null and alternative hypotheses are below. 
H0: The Dolphin Fluid Immersion Simulation® System and Air-fluidized treatment groups have 
equal differences in pressure ulcer microbiome.
H1: The Dolphin Fluid Immersion Simulation® System and Air-fluidized treatment groups have 
unequal differences in pressure ulcer microbiome.
7.4.2.4 Differences in qualitative and quantitative markers of inflammation in the pressure ulcer 
utilizing PCR and protein assays between tissue biopsies taken just prior to and following initial 
debridement, following any subsequent necessary debridements, and prior to operative closure.  
Differences will be calculated and displayed by treatment group and overall and then will be 
compared using a two-sample t-test.  
The null and alternative hypotheses are below. 
H0: The Dolphin Fluid Immersion Simulation® System and Air-fluidized treatment groups have 
equal differences in inflammatory markers.
H1: The Dolphin Fluid Immersion Simulation® System and Air-fluidized treatment groups have 
unequal differences in inflammatory markers.
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7.4.2.5 Differences in baseline patient characteristics including age, comorbidities, nutritional 
parameters, spasticity, medications, and ulcer history as well as the treatment group will be 
summarized and compared amongst patients who experience early and late pressure ulcer 
recurrences or wound-related complications.  Differences will be calculated and displayed using 
an aggregate of these complications or by individual complication, and then will be compared 
using Chi-Square or Fisher’s exact test for categorical variables and using a two-sample t-test for 
continuous variables.  Multivariate logistic regression analyses will be performed to identify 
statistically significant independent predictors of recurrence and wound-related complications. 
The null and alternative hypotheses are below.  
H0: Neither baseline patient characteristics nor the treatment group is associated with early or 
late pressure ulcer recurrence or the occurrence of a wound-related complication. 
H1: Baseline patient characteristics or the treatment group is associated with an increased or 
decreased risk of an early or late pressure ulcer recurrence or the occurrence of a wound-
related complication.
7.4.2.6 Differences in flap technique and surgeon guided descriptions of the tension of closure 
and potential dead space will be assessed and compared according to clinical outcome and 
presence of a complication.  Differences will be calculated and displayed by individual outcome 
and by the presence of a complication, and then will be compared using Chi-Square or Fisher’s 
exact test for categorical variables and using a two-sample t-test for continuous variables.  
Multivariate logistic regression analyses will be performed to identify statistically significant 
independent predictors positive and negative outcomes as well as complications. 
The null and alternative hypotheses are below.  
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H0: Flap technique, tension of the operative closure, or potential dead space is not associated 
with clinical outcomes or the presence of a complication.  
H1: Either flap technique, tension of the operative closure, or potential dead space are 
associated with clinical outcomes or the presence of a complication. 
7.4.2.7 Total costs including treatment costs, the costs of associated complications, the cost of 
hospital stay, and any other unforeseen costs during the two week study period following 
operative closure will be tabulated and compared between the Treatment and Control groups.
Differences will be calculated and displayed by treatment group and overall and then will be 
compared using a two-sample t-test.  
The null and alternative hypotheses are below. 
H0: The Dolphin Fluid Immersion Simulation® System and Air-fluidized treatment groups result 
in equal costs.
H1: The Dolphin Fluid Immersion Simulation® System and Air-fluidized treatment groups result 
in unequal costs.
7.4.2.8 Differences in quantitative measures of patient and nurse acceptability of the treatment 
and control arms will be tabulated and compared between the Treatment and Control groups.
Differences will be calculated and displayed by treatment group and overall and then will be 
compared using a two-sample t-test.  
The null and alternative hypotheses are below. 
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H0: The Dolphin Fluid Immersion Simulation® System and Air-fluidized treatment groups result 
in equal acceptability among patients and nurses.
H1: The Dolphin Fluid Immersion Simulation® System and Air-fluidized treatment groups result 
in unequal acceptability between patients and nurses.
7.4.2.9 The number of complications or additional therapeutic interventions will be assessed by 
patient phone interviews and be displayed by treatment group and overall and then will be 
modeled using a two-sample t-test.  
The null and alternative hypotheses are below. 
H0: The Dolphin Fluid Immersion Simulation® System and Air-fluidized treatment groups have 
equal numbers of complications and additional therapeutic interventions during the year 
following the two week study period. 
H1: The Dolphin Fluid Immersion Simulation® System and Air-fluidized treatment groups have 
unequal numbers of complications and additional therapeutic interventions during the year 
following the two week study period.
7.5. Safety Analyses
Safety analyses will be carried out using the Safety population to allow a benefit/risk 
assessment within the same study population.  
All AEs recorded during the course of the study will be coded according to the MedDRA 
(version 13.0) classification system.  An event will be considered as treatment emergent if the 
time of onset is on or after the initial debridement through Day 74.  Any event with an onsent on 
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the day of initial operative debridement where the time of onset is missing will be assumed to be 
treatment emergent. 
Number and percentage of treated subjects who experienced at least one adverse event in 
each system organ class by preferred term will be used to summarize all serious and non-serious 
adverse events.  Summary tables will be provided of incidences for all treatment emergent 
adverse events, treatment-related adverse events, adverse events by maximum severity, serious 
adverse events, and adverse events that led to study discontinuation.  In any given category (e.g. 
system organ class or preferred term) a subject will be counted only once.  If a subject has the 
same adverse event on multiple occasions, only the one with maximum severity will be 
presented.  The denominator for the calculation of percentages will be the number of subjects in 
the sub-arm of subjects being tabulated and not the number of events. 
7.6 Handling of Missing and Incomplete Data
There will be no imputations made to accommodate missing data.  All data recorded will 
be included in data listings.    
8. Study Discontinuation and Withdrawal of Study Subjects
8.1. Premature Discontinuation of the Study
If the clinical investigation is terminated prematurely or suspended, the IRB will be 
informed promptly and provided with the reason(s) for the termination or suspension by the 
Sponsor or by the clinical investigator.  If applicable, regulatory authorities and the personal 
physicians of the subjects will be informed by the clinical investigator.  
8.1.1 By Sponsor (Joerns)
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Joerns reserves the right to discontinue any clinical investigation for business or ethical reasons 
at any time, such as but not limited to:

The clinical investigation is not conducted in accordance with the approved protocol

Information on the investigational product causes doubt as to the benefit/risk ratio

Changes in medical practice limit utility of the data obtained from the study

Incidence or severity of AEs indicates a potential health hazard or poses an unreasonable 
risk to the study participants
8.1.2 By IRB
The IRB may choose to discontinue the clinical investigation if the: 

Clinical investigation is not conducted in accordance with the IRB’s requirements

Clinical investigation is associated with unexpected serious harm to subjects
8.2. Premature Discontinuation of the Subject
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the PI for safety, behavioral, or administrative reasons.  
If a subject does not respond to study telephone surveys, every effort should be made to contact 
the subject, per institutional protocol. 
In any circumstance, every effort should be made to document subject outcome.  The 
Investigator should inquire about the reason for withdrawal and follow up with the subject 
regarding any unresolved AEs.  Any related SAE occurring within 14 days following subject 
discontinuation must be reported to Joerns® and be followed up until stabilization or resolution.  
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If the subject withdraws from the study, and also withdraws consent for disclosure of 
future information, no further study evaluations will be performed, and no additional data will be 
collected.  The PI may retain and continue to use any data collected before such withdrawal of 
consent.
8.2.1 By Investigator
The Investigator may choose to discontinue a Subject from the study with or without their 
consent for any of the following:

Adverse Events

Non-compliance

Safety

Complications

Unforeseen events

Or for any reason that may, in the opinion of the Investigator, affect negatively the well 
being of the subject
If for any reason the subject is withdrawn from the clinical investigation, the Investigator will 
inform the subject accordingly.  
9. Potential Risks of Study Participation
9.1. Potential Risks Associated with the Investigational Product
All risks known or anticipated based on prior experience, risk analysis or reasonable 
grounds are listed in each product’s Instructions for Use.  This protocol document will be 
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updated in the presence of new information of relevance to the safety of the subject or the 
conduct of the study.  
10. Monitoring for Safety
The Investigator will perform safety monitoring in the following manner.  AEs will be 
captured at each study visit during treatment regardless of causality or severity.  All SAEs will 
be followed by the Investigator until resolution/stabilization.
10.1. Adverse Events
The intent of Joerns is to protect the safety of all subjects enrolled in this clinical 
investigation.  Broadly defined an AE is any undesirable clinical occurrence in a subject.  AEs 
will be 100% source-verified by the Joerns representative during each monitoring visit. 
The intensity of an AE will be classified as one of the following:
Definition of Intensity of Adverse Events
Intensity
Definition
Mild
Transient, does not interfere with Subject’s daily activities, does not require 
special treatment
Moderate
Interferes with Subject’s daily activities, requires simple therapeutic measures
Severe
Intolerable experiences, interruption of Subject’s daily activities, requires 
substantial therapy including medical or surgical intervention or hospitalization
The Investigator is responsible for completing the causality assessment.  The relationship of an 
AE to the device, comparator, or surgical incision will be categorized as one of the following:
Relationship of Adverse Events to the Device
Relationship
Definition
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Not Related
No relationship which makes a causal relationship incontrovertible (i.e. not 
related to the device)
Related
Definite temporal association exists, clinical experience makes the relationship 
definite and certain
10.2. Serious Adverse Events
A SAE is an AE that meets one or more of the following criteria:

fatal

life-threatening

results in an unanticipated or prolonged hospitalization

results in a significant and persistent disability/incapacity
10.3. Anticipated Events
Anticipated AEs for this study include but are not limited to periwound skin maceration, 
wound recurrence after definitive closure, hematoma, seroma, and surgical site infection.  These 
events may result in therapeutic interventions, including surgical drainage, surgical incision 
packing, debridement, and reoperation.  Although anticipated, these occurrences are considered 
AEs and should be documented appropriately.
10.4. Investigator Reporting Requirements
The Investigator has the primary responsibility for safety of subjects under his or her 
care.  In this function, he/she should routinely monitor each subject for the occurrence of any 
AE.  For every AE that occurs, the causal relationship will be determined.  If the device, 
comparator, or study treatment relatedness is found, then a full description of the event should be 
recorded including the data of onset, time course, severity, action taken regarding the study 
treatment, outcome, and any treatment applied.  
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The Investigator should list the specific diagnosis, disease, or syndrome rather than 
associated signs and symptoms.  However, if the Investigator does not consider an observed or 
reported sign or symptom a component of a specific disease or syndrome, it should be recorded 
as a separate AE.  Clinical syndromes associated with the findings of laboratory abnormalities 
are to be recorded appropriately (e.g. bacterial infection of the surgical incision instead of 
increase in bacterial load) as AEs.  
10.5. Device Malfunction
Device malfunction means the failure of a device to meet its performance specifications 
or otherwise perform as intended.  Performance specifications include all claims made in the 
labelling for the device.  The intended performance of a device refers to the intended use for 
which the device is labelled or marketed. 
Device malfunction may or may not result in the subject experiencing harmful effect.  All 
adverse device effects (ADEs)/unanticipated adverse device effects (UADEs) associated with a 
device failure are by definition device related and will be recorded and followed by an 
Investigator until stabilization or resolution.  Device malfunctions that are not related to an 
adverse event will be reported to Joerns within 2 business days.  
10.6. Adverse Event Related Withdrawal
Subject withdrawal due to an AE should be distinguished from withdrawal due to other 
reasons by appropriate documentation. 
10.7. Follow-up of Subjects with Adverse Events
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For subjects who are experiencing ongoing unresolved adverse events at the time of their 
study completion or early discontinuation from the study, the Investigator should schedule one or 
more follow-up visits as appropriate to follow the subject until the adverse event is resolved, or 
determined to be chronic.  
11. Quality Control and Quality Assurance
11.1 Training on Study Products and Procedures
The Investigator and staff will be trained on the study protocol, the investigational 
device(s), and any specialized procedures prior to and/or during the initiation visit.  Sponsor will 
provide clinical support to site staff for any questions or concerns related to treatment plans; 
however, the Sponsor will not have influence on subject clinical care. 
11.2 Sponsor
The Sponsor will be responsible for implementing and maintaining quality assurance and 
a quality control system to ensure that the data generated are recorded and reported in 
accordance with established procedures.  
Data from case report forms (CRFs) and other external data (i.e. laboratory data) will be 
entered into a clinical database.  Quality control and data validation procedures will be applied to 
ensure the validity and accuracy of the clinical database.  
The clinical database will be reviewed and checked for omissions, apparent errors, and 
values requiring further clarification.  Data queries requiring clarification will be documented 
and returned to the site for resolution.  Only authorized personnel will make corrections to the 
clinical database, and all corrections will be documented in an audit trail. 
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All agreements made by the Sponsor and Investigator will be reduced to a written 
document and serve as a separate contract and/or as an amendment to the protocol.  
During the course of the clinical investigation, an amendment to the clinical investigation 
protocol may be necessary.  Only the Sponsor is allowed to amend this protocol.  Any 
amendments or modifications must be approved by the IRB prior to clinical investigation staff 
implementation, unless the modifications are implemented to eliminate immediate hazard to the 
subject.  The research site will receive the following for their IRB submission:

A memorandum outlining the changes and justification for modifications

An updated protocol

Changes to ICF template (if necessary)
11.3. Investigator
The Investigator assumes full responsibility for performance of the clinical investigation 
in accordance with the Clinical Trial Agreement, this protocol, IRB requirements, and applicable 
requirements to the jurisdiction in which the clinical investigation is being conducted. 
12. Ethics
12.1 Institutional Review Board (IRB)
The Investigator must submit this protocol and all applicable supporting forms and 
documents to the IRB, and is required to forward to the Sponsor a copy of the written and dated 
approval/favorable opinion signed by the Chairman of the IRB committee.  The study (study 
number, protocol title, and version number), the documents reviewed (e.g. protocol and ICF), 
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and the date of the review should be clearly stated on the written IRB approval/favorable 
opinion. 
The ICF (plus additional forms, as applicable) used by the Investigator for obtaining the 
Subject’s informed consent should be reviewed and approved by the Sponsor prior to submission 
to the IRB for approval/favorable opinion.
A progress report is sent by the Investigator to the IRB annually or as specified by the 
IRB and a summary of the clinical investigation outcome(s) is reported at the end of the clinical 
investigation.  
13. Data Handling and Recording
13.1. Data Quality Assurance
Steps to be taken to ensure the accuracy and reliability of data include review of protocol 
procedures with the Investigator and associated personnel before the study commences and 
periodic on-site monitoring visits by the Sponsor.  Guidance for CRF completion will be 
provided and reviewed with the study personnel before the start of the study.  The Sponsor will 
review CRFs for completeness during on-site monitoring visits and after their return to the 
Sponsor; any discrepancies will be resolved with the Investigator or designee, as appropriate.  
The data will be entered into the clinical study database and verified for accuracy
13.2. Data Collection
The study CRF is the primary data collection instrument for this study.  All data 
requested on the CRF must be recorded.  All missing data must be explained. 
13.3. Data Handling
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The Investigator is responsible for compilation and verification of the study data, 
retention of the clinical study database, performance of statistical analysis, and preparation of the 
data reports.  
13.4. Record Storage and Retention
13.4.1 Investigator
In accordance with the Clinical Trial Agreement, the Investigator shall maintain all study 
documentation in its possession and/or control and institute measures to prevent accidental or 
premature destruction of any data and/or documents related to the study. 
After formal discontinuation of the clinical investigation, the Investigator shall retain the 
clinical trial documentation produced for a minimum of three (3) years or in accordance with the 
regulations in effect for the jurisdiction. 
The investigator shall allow Sponsor and/or Sponsor’s representatives to have access to 
the clinical investigation documents as defined in the Clinical Trial Agreement.
13.4.2 Sponsor
The Sponsor shall maintain all study documentation in its possession and/or control and 
institute measures to prevent accidental or premature destruction of any data and/or documents 
related to the study. 
The Sponsor shall retain the study documentation according to Title 21 CFR 812.140 6(d):
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An investigator or sponsor shall maintain the records required by this subpart 
during the investigation and for a period of 2 years after the latter of the following 
two dates: The date on which the investigation is terminated or completed, or the 
date that the records are no longer required for purposes of supporting a 
premarket approval application or a notice of completion of a product 
development protocol.
14. Confidentiality of the Study
Pursuant to the terms and conditions set forth in the Clinical Trial Agreement, the 
Investigator and staff involved in the Study shall consider all information, results, discoveries, 
records accumulated, acquired, or deduced in the course of the study, other than that information 
to be disclosed by law, as confidential and shall not disclose any such results, discoveries, 
records to any third party without informing the Sponsor.  Refer to the Clinical Trial Agreement 
for more specific terms and conditions.
15. Publication Policy
All publications and/or presentations are subject to the discretion of the Investigator.  The 
Investigator will maintain complete control of the data and illustrations to be utilized in 
publications.  The Sponsor will be informed prior to data publication. 
16. References
1.
International NPUAP/EPUAP Pressure Ulcer Classification System. In National 
Pressure Ulcer Advisory Panel, European Pressure Ulcer Advisory Panel and Pan Pacific 
Pressure Injury Alliance. Prevention and Treatment of Pressure Ulcers: Clinical Practice 
Guideline. Emily Haesler (Ed.) Cambridge Media: Osborne Park, Western Australia; 
2014.
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2.
Allman, R.M., Pressure ulcers among the elderly. N Engl J Med, 1989. 320(13): p. 850-
3.
3.
Staas, W.E., Jr. and H.M. Cioschi, Pressure sores--a multifaceted approach to prevention 
and treatment. West J Med, 1991. 154(5): p. 539-44.
4.
Gordon, M.D., et al., Review of evidenced-based practice for the prevention of pressure 
sores in burn patients. J Burn Care Rehabil, 2004. 25(5): p. 388-410.
5.
Kuhn, B.A. and S.J. Coulter, Balancing the pressure ulcer cost and quality equation. 
Nurs Econ, 1992. 10(5): p. 353-9.
6.
Changes to the Hospital Inpatient Prospective Payment Systems and Fiscal Year 2009 
Rates, D.o.H.a.H.S.C.f.M.M.S. Program., Editor. 2008.
7.
Voss, A.C., et al., Long-term care liability for pressure ulcers. J Am Geriatr Soc, 2005. 
53(9): p. 1587-92.
8.
VanGilder, C., et al., Body mass index, weight, and pressure ulcer prevalence: an 
analysis of the 2006-2007 International Pressure Ulcer Prevalence Surveys. J Nurs Care 
Qual, 2009. 24(2): p. 127-35.
9.
Kottner, J., A. Gefen, and N. Lahmann, Weight and pressure ulcer occurrence: a 
secondary data analysis. Int J Nurs Stud, 2011. 48(11): p. 1339-48.
10.
Johansen, E., et al., Pressure ulcer risk assessment and prevention: What difference does 
a risk scale make? A comparison between Norway and Ireland. J Wound Care, 2014. 
23(7): p. 369-78.
11.
Beeckman, D., et al., A systematic review and meta-analysis of incontinence-associated 
dermatitis, incontinence, and moisture as risk factors for pressure ulcer development. 
Res Nurs Health, 2014. 37(3): p. 204-18.
12.
Garcia-Fernandez, F.P., et al., A new theoretical model for the development of pressure 
ulcers and other dependence-related lesions. J Nurs Scholarsh, 2014. 46(1): p. 28-38.
13.
Graves, N., F. Birrell, and M. Whitby, Effect of pressure ulcers on length of hospital stay. 
Infect Control Hosp Epidemiol, 2005. 26(3): p. 293-7.
14.
Russo, C.A., C. Steiner, and W. Spector, Hospitalizations Related to Pressure Ulcers 
Among Adults 18 Years and Older, 2006: Statistical Brief #64, in Healthcare Cost and 
Utilization Project (HCUP) Statistical Briefs. 2006, Agency for Health Care Policy and 
Research (US): Rockville (MD).
15.
Ratliff, C.R. and N. Tomaselli, WOCN update on evidence-based guideline for pressure 
ulcers. J Wound Ostomy Continence Nurs, 2010. 37(5): p. 459-60.
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