Prophylactic Negative Pressure Wound Therapy in Obese Women at Cesarean: a Multicenter Randomized Trial
Phase: NA
Conditions: Surgical Wound Infection, Cesarean Section
Sponsor: Indiana University

 
 
 
2021 
Preventing Adverse 
Incisional Outcomes at 
Cesarean Multicenter Trial 
PREVENA – NCT03009110 
PROTOCOL AND STATISTICAL ANALYSIS PLAN 

 
 
Prophylactic Negative Pressure Wound Therapy in Obese Women at Cesarean:           
a Multicenter Randomized Trial 
Short Title: Preventing Adverse Incisional Outcomes at Cesarean Multicenter Trial 
 Acronym: “Prevena-C Multicenter Trial” 
STUDY PROTOCOL 
 
Version 1.9 
 
Date:   
            
 
August 29, 2019 
 
Funding Agency:  
 
National Institute of Child Health and Human Development  
 
Principle Investigator: 
 
Methodius G. Tuuli, MD, MPH 
 
Study Sites: 
 
Clinical Coordinating Center  
Indiana University 
 
 
 
 
 
PI: Methodius Tuuli, MD, MPH (Steering Committee Chair) 
 
 
 
 
 
 
Data Management Center 
 
Washington University in St Louis 
 
 
 
 
 
Co-I: Esther Lu, PhD (Study Statistician) 
 
Study Site #2  
 
 
Washington University 
Site PI: Ebony Carter, MD, MPH 
Co-I: David Warren, MD, MPH 
 
 
 
 
 
Study Site #3  
 
 
University of Alabama at Birmingham 
Site PI: Lorie Harper, MD, MSCI  
Co-I: Alan Tita, MD, PhD  
 
Study Site #4  
 
 
Ochsner Medical Center 
Site PI: Sherri Longo, MD 
 
Study Site #5  
 
 
Mercy Hospital in St Louis (Closed) 
Site PI: Amanda Trudell, MD, MSCI 
 
 
 
Economic Analysis:  
 
Oregon Health Sciences University 
 
 
 
 
 
PI: Aaron Caughey, MD, MPP, MPH, PhD  
 
 
 
 
DSMB: 
 
 
 
Sindhu Srinivas, MD, MSCE (Chair) 
Alison Cahill, MD, MSCI 
Jenifer Allsworth, PhD 
 

 
 
 
Table of Contents 
Protocol Summary 
 
1.Introduction 
1 
     Abstract 
1 
     Specific Aims 
2 
     Purpose of the Protocol 
2 
2.Background 
3 
3.Study Design 
10 
     Research Questions 
10 
     Design and Rationale 
10 
     Eligibility Criteria 
11 
4.Study Procedures 
12 
     The Prevena™ Incision Management System 
12 
     Provider Training  
13 
     Screening 
14 
     Randomization  
15 
     Procedures 
15 
         Schedule of Events 
15 
         Preoperative 
15 
         Intraoperative 
16 
         Postoperative 
18 
     Follow-Up 
20 
     Outcome Measures 
20 
          Primary Outcomes 
20 
          Secondary Outcomes 
21 
5.Data Management  
23 
6. Data Analysis 
25 
7.Safety Monitoring 
31 
8.Study Administration 
41 
9. Protection of Human Subjects 
44 
10.Study Timetable 
47 
11. References 
48 

 
 
PROTOCOL SUMMARY 
 
Prophylactic Negative Pressure Wound Therapy in Obese Women at Cesarean: a multicenter Randomized Trial 
(Prevena-C Multicenter Trial) 
Objective: To assess the effectiveness, safety and cost-effectiveness of prophylactic NPWT in reducing the rate of SSIs after cesarean in obese women 
Organization: 
Study Sites – 1) Indiana University (IU Health Methodist Hospital & Eskenazi Hospital), Indianapolis Indiana; 2) Washington University in St. Louis School of 
Medicine; 3) University of Alabama at Birmingham; 4) Ochsner Medical Center, New Orleans 5) Mercy Hospital in St. Louis (Closed) 
Study Coordinating Center: Indiana University 
 
Data Management Center: Washington University in St. Louis School of Medicine 
Steering Committee – Tuuli (PI, chair), each of the site PIs, Caughey 
Data Safety and Monitoring Board – Sindhu Srinivas, MD, MSCE(chair); Alison Cahill, MD, MSCI; Jenifer Allsworth, PhD  
Design: Multicenter Randomized Clinical Trial 
 
Inclusion criteria: 
1. Pre-Pregnancy BMI ≥ 30 Kg/m2 (BMI at first prenatal visit) 
2. Gestational age ≥ 23 weeks  
3. Scheduled/non-labor or unscheduled/labor cesarean delivery  
Exclusion criteria:  
1. Unwilling or unable to provide consent 
2. Non-availability for postoperative follow-up  
3. Contraindication to NPWT  
 Pre-existing infection around incision site 
 Bleeding disorder 
 Therapeutic anticoagulation 
 Allergy to any component of the dressing (e.g., silver, silicone, 
adhesive tape) 
 Prior irradiated skin 
Allocation:  Computer generated block randomization, stratified by study 
                    site, BMI category, scheduled/unscheduled cesarean 
Sample size: 2850 (Standard dressing=1425, Prophylactic NPWT=1425) 
          Assumptions 
1. Power=80% for primary outcome 
2. Type 1 error=5% (2-sided) 
3. Primary outcome  
-10% event rate with standard wound dressing 
-Anticipated 30% 
relative difference 
(anticipated 7% 
event rate with 
prophylactic NPWT) 
4. 5% loss to follow up  
      Interventions: 
1. Standard wound dressing 
2. Prophylactic NPWT with 
PrevenaTM (Peel & Place)   
 
Management Protocols:   
1. Prophylactic NPWT with PrevenaTM (Peel & Place)   
o 
Place after skin closure 
o 
Remove on postop day #4, day of hospital discharge, or by day 7 if 
patient remains hospitalized 
2. Standard wound dressing 
o 
Place after skin closure 
o 
Remove in approximately 24 - 48 hours 
Outcome Measures: 
Primary: Superficial or deep SSI within 30 days based on CDC criteria 
Secondary: 
 
 
Individual components of the primary outcome (superficial or deep SSI) 
 
Organ space SSI (endometritis) 
 
Other individual wound complications: dehiscence ≥2 cm, hematoma, 
seroma 
 
Composite of any wound complications 
 
Pain and satisfaction scores at discharge, postoperative day 30 
 
Patient satisfaction with aesthetic appearance (scale of 0 - 10) at 
postoperative day 30 
 
Healthcare resource utilization: physician office or ED visits, antibiotics 
for SSI, hospital readmission for SSIs, home health for SSI, wound clinic 
for SSI 
 
Adverse events: skin blistering, allergic skin reactions, wound bleeding  
Cost-effectiveness analysis 
 
Incremental cost per case of SSI prevented 
 
Incremental cost per Quality-adjusted Life-year (QALY). 
Data Analysis:  
  Primary: Intention-to-treat 
  Secondary: Pre-specified subgroup, adjusted analyses, risk factors  
Study Timetable: 
 Recruitment:  6 months to 54 months 
 Interim Analysis:  @ N=1425 (50%) and N=2138 (75%)

 
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1. Introduction 
1.1. Abstract 
The Prophylactic Negative Pressure Wound Therapy in Obese Women at Cesarean Trial is a large 
pragmatic multi-center randomized clinical trial designed to evaluate the effectiveness, safety and cost-
effectiveness of prophylactic negative pressure wound therapy (NPWT) – a closed, sealed system that 
applies negative pressure to the wound surface via a single-use, battery-powered, portable device – to 
decrease surgical site infections (SSIs) in obese women.  Experimental evidence suggests that NPWT 
promotes wound healing by removing exudate, approximating the wound edges, and reducing bacterial 
contamination.  Obesity (body mass index [BMI] ≥30kg/m2) increases the risk for both cesarean delivery 
and SSIs compared to non-obese women.  The increased risk of SSIs is in part due to the increased 
thickness of the subcutaneous space, allowing collection of exudates and increasing tension on wound 
edges, promoting the growth of bacteria, and leading to wound infection and breakdown. Thus, 
prophylactic NPWT may be particularly effective in this patient population.  During the 5-year project 
period, collaborating perinatal centers will randomize 2850 obese women undergoing cesarean delivery 
to receive either prophylactic negative pressure wound therapy with the PrevenaTM device or standard 
wound dressing.  Women will be followed up to 30 days postoperatively to ascertain study outcomes. 
The primary outcome for the trial is superficial or deep SSI after cesarean according to the CDC 
National Healthcare Safety Network definitions. We will also assess other wound complications, 
adverse events potentially attributable to NPWT and incremental cost per case of SSI prevented and 
per quality-adjusted life year (QALY). 
 
 
 
 
 

 
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1.2. Specific Aims 
Primary Aim: Determine the effectiveness of prophylactic NPWT in reducing the rate of SSIs after 
cesarean in obese women.  We hypothesize that obese women will have lower rates of SSIs after 
cesarean with use of prophylactic NPWT than with standard care. 
Secondary Aim#1: Assess the safety of prophylactic NPWT in obese women as measured by 
frequency of adverse events including skin blisters, allergic skin reactions, and wound bleeding.  
We hypothesize that the rate of adverse events will not be significantly higher with use of 
prophylactic NPWT than with standard care. 
Secondary Aim#2: Evaluate the cost-effectiveness of prophylactic NPWT compared with 
standard wound dressing in obese women as measured by the incremental cost per case of SSI 
prevented and per quality-adjusted life year (QALY).  We hypothesize that prophylactic NPWT 
in obese women at cesarean will be cost-effective. 
1.3. Purpose of the Protocol 
 
This protocol describes the background, design, and organization of the trial and represents a 
written agreement between study investigators.  It will be reviewed and approved by the Data Safety 
and Monitoring Board (DSMB) and the Institutional Review Boards (IRBs) of each center prior to onset 
of recruitment. A Manual of Operations and Data Collections Forms will supplement this protocol 
with further details of study procedures. 
 
 

 
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2. Background 
2.1. Introduction 
SSIs are now the most common group of healthcare associated infections (HAIs) and are a 
significant cause of preventable morbidity and mortality in the United States.1  These infections result 
in significant patient suffering and excess health care costs up to $10 billion each year.1 For these 
reasons, prevention of HAIs is a top priority for the US Department of Health and Human Services and 
the Institute of Medicine.2,3  Although several initiatives target HAIs, few are directed at SSIs after 
cesarean despite the fact that cesarean is the most common major surgical procedure performed in 
women.  In 2013, 1.3 million cesareans were performed in the US and up to 12% of these were 
complicated by SSIs.4,5  Puerperal infection is the 4th most common direct cause of maternal mortality 
in the US and one of the most common causes of morbidity.6  Additionally, puerperal infection is an 
indirect or aggravating factor in many maternal deaths attributed to other causes.  Moreover, cesarean 
delivery is the most important risk factor for puerperal infection.2   
Obesity (BMI≥30 kg/m2) further aggravates the problem of SSIs after cesarean: obese women 
are both more likely than non-obese women to deliver by cesarean7-9 and are also at higher risk of 
SSIs.10,11  Obesity complicates over 33% of pregnancies and morbid obesity (BMI ≥ 40 kg/m2) 
complicates as many as 10% of pregnancies in the US.  The trends of both increasing prevalence of 
obesity as well as increasing incidence of cesarean suggest that the burden of post-cesarean infections 
will continue to increase in the US. 
2.1.1. Pathophysiology of SSIs after Cesarean in Obese Women 
 
The mechanism for increased SSI risk in obese women is likely multifactorial.  First, an excess 
of adipose tissue may result in dysregulation of the immune system, impairing chemotaxis and altering 
macrophage differentiation.12  Obese women may also have diabetes and other metabolic 
derangements that further impair the immune system and thus the inflammatory phase of the wound 
healing process.  Second, obesity decreases adipose tissue blood flow and alters collagen structure 

 
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and function,13,14 limiting infiltration of the space by chemokines, macrophages and growth factors 
necessary for the first and second stages of wound healing.  Obesity also impairs the penetration of 
preoperative antibiotics, resulting in tissue antibiotic levels below the minimal inhibitory concentration 
for pathogenic bacteria.15  Third, the potential subcutaneous dead space allows accumulation of serous 
fluid and hematomas that serve as a nidus for infection.16  Physiologic changes of pregnancy and 
intravenous fluids given during the puerperium exacerbate the accumulation of serous fluid in the 
subcutaneous dead space after cesarean.  Fourth, the thickened subcutaneous tissue places additional 
mechanical stress on the wound, increasing both superficial stress and lateral tension.  The additional 
shear stress reduces the apposition of cells in the incision, creating additional potential space and 
increasing the risk of wound dehiscence and infection.  Finally, the overhanging pannus in obese 
women, especially over the site of Pfannenstiel incisions, creates a micro-environment conducive to 
bacterial proliferation. 
2.1.2. Prophylactic Negative Pressure Wound Therapy 
 
Negative pressure wound therapy (NPWT) is a closed, sealed system that applies negative (or 
sub-atmospheric) pressure to the wound surface.  Used since the 1990s to treat open wounds, 
experimental evidence suggests that NPWT promotes wound healing by removing exudates, 
approximating the wound edges, and reducing bacterial contamination.17-27  Two brands of a modified, 
single-use, battery-powered, portable NPWT devices PrevenaTM (KCI USA, San Antonio, TX) and 
PICOTM (Smith & Nephew, Hull, UK) were recently FDA-cleared for prophylactic application after wound 
closure at the time of surgery.  Although the precise mechanism of action of prophylactic NPWT is 
unclear, experimental evidence suggests that NPWT reduces bacterial contamination, edema, and 
exudates while increasing microvascular blood flow and promoting granulation tissue by inducing 
mechanical stress that promotes cell growth.28-31  Computer and physical models of NPWT applied to 
closed incisions demonstrate a decrease in lateral tensile stress by 50% and in shear stress by more 
than 75%, leading to improved apposition of wound edges.32  Given the proposed mechanisms of 

 
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increased SSI in obese women and the potential mechanism of action of prophylactic NPWT, we 
hypothesize that prophylactic NPWT will be particularly effective in this population. 
2.1.3. Existing Data on Prophylactic NPWT 
Non-Obstetric Patients 
Prior studies of NPWT have largely been limited to cohort studies33-37 and small randomized 
trials.38-41  Whereas many demonstrated benefit in reducing SSIs and other wound complications, many 
studies were limited by small samples sizes and confounding by indication.  A 2014 Cochrane review 
of seven randomized trials compared prophylactic NPWT to standard dressing among patients 
undergoing orthopedic and general surgical procedures. Data from only three of the trials could be 
combined in a meta-analysis, which showed no significant differences in the rate of SSI.42  However, a 
fourth trial, in which data were analyzed by wound rather than by subject, showed a statistically 
significant 50% reduction in SSI in the NPWT group (14/144 (9.7%) versus 23/122 (18.9%), relative 
risk 0.52, 95% confidence interval 0.28-0.96).  The authors concluded that “there is an urgent need for 
suitably powered, high-quality trials to evaluate the effects of the newer NPWT products that are 
designed for use on clean, closed surgical incisions.”  No studies of prophylactic NPWT after cesarean 
were included in this review. 
Obstetric Patients 
We identified three retrospective cohort studies and one pilot randomized trial in a systematic 
review of studies on prophylactic NPWT in obese women after cesarean43-46: (Table 1).  Two of the 
retrospective cohort studies compared obese women who received prophylactic NPWT after cesarean 
to historical controls who received standard dressing. Both studies demonstrated a dramatic reduction 
in SSIs, reporting no SSIs in the intervention group but 10.4% and 12.0% in the standard dressing 
controls.43,44  The third retrospective study included women who had labored prior to cesarean with at 
least one additional risk factor for SSI (obesity, preeclampsia, and chorioamnionitis). In this study 

 
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prophylactic NPWT was associated with a statistically significant reduction in the risk of wound infection 
(2.7% versus 11.5%; RR 0.24, 95% 0.07, 0.77; P=0.006) and endometritis (0.9% vs 6.7%, p=0.023).46   
 
 
 
Table 1: Published studies on use of prophylactic NPWT at cesarean in obese women 
 
Chaboyer et al recently published a pilot randomized trial in which 87 obese women undergoing 
elective cesarean were randomized to prophylactic NPWT or standard dressing.45  Use of prophylactic 
NPWT was associated with a statistically non-significant 19% decrease in SSI (22.7% vs 27.9%; RR 
0.81, 95% CI 0.38-1.68).  The authors also found no differences in the frequencies of adverse events 
(7/44 [15.9%] with NPWT vs 7/43 [16.3%] with standard dressing), and all were minor (skin blisters, 
erythema, bruising, and wound bleeding). Although more methodologically sound than the others, this 
 
Study 
 
Design 
 
Device 
 
Inclusion 
Surgical site 
infections,  
n/N (%) 
Relative 
Risk 
(95%CI) 
 
Limitations 
NPWT 
Control 
Mark 
et al.,2013 
 
Retrospective 
cohort 
Prevena 
BMI>45 
0/21 
(0%) 
5/48 
(10.4%) 
 
0.20 
(0.01, 3.50) 
Small sample size, 
possible selection bias 
and confounding by 
indication 
Bullough 
et al.,2014 
 
Retrospective 
cohort 
PICO 
BMI>35 
0/50 
(0%) 
6/50 
(12%) 
 
0.08 
(0.00, 1.33) 
Small sample size, 
possible selection bias 
and confounding by 
indication 
Swift  
et al.,2015 
Retrospective 
cohort study 
Prevena 
BMI>30 
or other 
risk 
factors 
3/110 
(2.7%) 
24/209 
(11.5%) 
 
0.24 
(0.07, 0.77) 
Non-randomized 
design, possible 
confounding, modest 
sample size 
Chaboyer 
et al.,2015 
Pilot 
Randomized 
Controlled 
Trial 
PICO 
BMI>30 
10/44 
(22.7%) 
12/43 
(27.9%) 
 
0.81 
(0.39, 1.68) 
Small sample size, 
included only elective 
cesareans, possible 
confounding 

 
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study was limited by including only elective cesareans, the small sample size and differences in 
prognostic baseline characteristics between the two groups.   
Taken together, these studies suggest a 65% decrease in SSIs after cesarean with prophylactic 
NPWT (random effects model: pooled RR 0.35, 95% CI 0.12-1.04). Although results of these studies 
are promising, the small sample sizes, between-study heterogeneity, and methodological limitations 
preclude definitive conclusions on the effectiveness of prophylactic NPWT in obese women after 
cesarean. 
Preliminary Study#1 
We conducted a retrospective 
cohort study at one of the proposed 
study sites (University of Alabama at 
Birmingham) where some physicians 
use the NPWT in select morbidly 
obese women undergoing cesarean. 
The charts of all women with a BMI 
≥40 kg/m2 undergoing cesarean 
since NPWT became available were 
reviewed. 
Of 
762 
subjects, 
15 
received NPWT.  Women who received NPWT weighed more (BMI 68.8 versus 50.0, P<0.01) and were 
more likely to have medical co-morbidities than those who did not receive NPWT. The risk of SSI was 
remarkably lower with prophylactic NPWT (0% [0/15] versus 11.9% [89/747], P=0.16) (Fig.1). Although 
the study is limited by the non-randomized design, small sample size, and selection bias, the results 
suggest that prophylactic NPWT may be effective in reducing SSIs after cesarean in obese women.  
Preliminary Study#2 
We conducted a pilot RCT (planned N=120) at Washington University Medical Center47  aimed 
at: i) assessing the willingness of obese patients to participate in an RCT of prophylactic NPWT after 

 
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cesarean, and ii) testing the logistics needed for the trial. We obtained IRB approval for the trial and 
developed a study protocol. Obese women in labor completed a survey and 67% stated willingness to 
participate in the study. We consented and randomized 120 obese patients undergoing cesarean in 6 
months.  
 
2.2. Adverse Effects of Prophylactic NPWT 
The Single Use Prophylactic Negative Pressure Wound Therapy System received FDA 
marketing approval in 2012.  As of September 2015, we identified two reports on the FDA website of 
blistering at the site of application from the PICO device.  A third report of a minor burn from the PICO 
pump device occurred in a patient after neurosurgery while still unconscious. The patient was found to 
have been lying on the pump device for a prolonged period of time.  
A high rate of skin blisters was reported when NPWT was used after orthopedic surgery, but not 
with other surgical procedures. This was attributed to use of the adhesive dressing in the setting of 
marked swelling and edema48. Case series suggest approximately 10-15% rate of skin irritation and 
blisters at the device application site. The majority (~90%) did not require treatment beyond removal of 
the device.49,50 Moreover, adverse events noted with NPWT after cesarean were minor and comparable 
in frequency to standard dressing51.  
2.3. Cost-benefit of Prophylactic NPWT 
The current FDA-cleared prophylactic single-use NPWT devices cost between $200 (PICO™) 
and $500 (Prevena™) per unit and are increasingly being used after cesarean. Given the cost, 
prophylactic NPWT must be shown in an independent, suitably powered, high-quality trial to improve 
clinical outcomes to justify widespread use52. However, if proven to be effective at reducing SSIs after 
cesarean, use of the device may not only be cost-effective, but cost-saving. Two cost-effectiveness 
analyses of prophylactic NPWT have recently been published suggesting that use prophylactic NPWT 
after cesarean may be cost effective under a range of conditions. However, because data on its 

 
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effectiveness at cesarean are lacking, the cost-effectiveness analyses were based on data extrapolated 
from other surgical procedures49,53. In addition to the effectiveness data this trial will produce, the 
accompanying cost-effectiveness analysis will aid decision-making on general clinical use52. 
2.4. Rationale for the Trial 
 
Infection is one of the top five causes of pregnancy-related death and morbidity in the US and 
around the world. As rates of cesarean - the strongest risk factor for puerperal infection - continue to 
rise, the burden of infection is anticipated to increase.  Obese women are at particularly high risk of 
infection after cesarean.  Despite the dramatically increased risk of SSI in obese women, no specific 
intervention exists in this population.  Preliminary data from published retrospective cohorts and small 
randomized trials, as well as our pilot data suggest that prophylactic NPWT may decrease SSI in obese 
women undergoing cesarean.  Therefore, given 1) the persistent high risk of infection and attendant 
individual and public health costs among obese women undergoing cesarean, 2) the increasing trend 
in both cesarean and obesity, 3) preliminary data suggesting the effectiveness of NPWT for preventing 
SSI, and 4) increasing use of NPWT devices with healthcare cost implications, a multicenter trial 
evaluating the effectiveness, safety and cost-effectiveness of prophylactic NPWT after cesarean in 
obese women is important and timely. 
 

 
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3. Study Design 
3.1. Research Questions 
Primary Question 
Compared to standard wound dressing, does the use of prophylactic NPWT reduce the risk of 
surgical site infection after cesarean in obese women? 
Hypothesis: Compared to standard wound dressing, prophylactic NPWT reduces the incidence of 
post-cesarean surgical site infection in obese women. 
Secondary Question 1 
Is the use of prophylactic NPWT associated with increased adverse events such as skin 
blisters, allergic reaction, wound bleeding? 
Hypothesis: Compared to standard wound care, prophylactic NPWT will not be associated with 
a significantly higher incidence of adverse events. 
Secondary Question 2 
Is the use of prophylactic NPWT after cesarean in obese women cost-effective? 
Hypothesis: Prophylactic NPWT will be a cost-effective intervention for the prevention of 
surgical site infections after cesarean in obese women. 
3.2. Design and Rationale 
This is a pragmatic multicenter randomized controlled trial. We chose a randomized controlled 
trial, the ‘gold standard’ of clinical research design, with the goal of obtaining the highest quality 
evidence to inform clinical practice. The broad inclusion criteria and evaluation of effects of typical 
use of prophylactic NPWT make this a pragmatic trial. The multicenter design and inclusion of both 
academic and community hospitals in two regions of the U.S. with high rates of obesity increase 
generalizability and direct application of the findings54. We will follow the Consolidated Standards of 
Reporting Trials (CONSORT) guidelines in the conduct and reporting of this trial55. Analysis will follow 
the intention-to-treat principle. By random allocation, patients will receive either prophylactic NPWT or 

 
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standard wound care after cesarean delivery.  The remainder of perioperative care will be similar for 
both arms including the administration of standard preoperative antibiotics within 60 minutes prior to 
skin incision, skin preparation with chlorhexidine alcohol or povidone-iodine solution, and clipping 
(rather than shaving) of hair as needed prior to incision. 
3.3. Eligibility Criteria 
3.3.1. Inclusion Criteria 
 Gestational age ≥23 weeks  
 Pre-pregnancy BMI ≥ 30 Kg/m2 (based on BMI at first prenatal visit, but BMI at delivery will also 
be collected) 
 Undergoing scheduled or unscheduled cesarean delivery 
3.3.2. Exclusion Criteria 
 Patient unwilling or unable to provide consent 
 Non-availability for postoperative follow up  
 Contraindication to NPWT applicable to women undergoing cesarean 
o Pre-existing infection around incision site 
o Bleeding disorder 
o Therapeutic anticoagulation 
o Allergy to any component of the dressing including silver, silicone and adhesive tape 
o Prior irradiated skin 
 
 
 
 
 
 

 
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4. Study Procedures 
4.1. The Prevena™ Incision Management System (Peel & Place) 
The Prevena™ Incision Management System incorporates all of the functional elements of 
NPWT that are necessary for management of closed surgical incisions. The system has the added 
advantages of being simple in concept and having an anatomically adaptable peel-and-place 
dressing which is uniquely designed to be skin-friendly. The dressing is easy to apply and use in the 
operating room (OR) by the surgeon, study staff or surgical staff. The system may also transition from 
the OR to the hospital and/or outpatient setting for use by multiple care takers.   
Figure 1: The Prevena™ Incision Management System (Peel & Place) 
 
The Prevena Incision Management System consists of the following components:  
o The Prevena™/ Prevena PLUS™ Incision Management System that is applied over clean 
sutured or stapled incisions in a simple peel-and-place process and applies continuous 
negative pressure at 125 mmHg through the dressing to the incision site. The Prevena™ 

 
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Incision Management System accommodates incisions up to 20 cm in length and the Prevena 
PLUS™ Incision Management System accommodates incisions up to 35 cm in length.   
o The dressing has a built-in pressure indicator that when compressed indicates that the 
negative pressure in the system is between -75mmHg to -125mmHg. A raised pressure 
indicator button indicates that the negative pressure is less than 75mmHg.  
o A polyurethane coated, polyester fabric interface layer with 0.019% ionic silver wicks fluid from 
the skin surface. The silver is not intended to treat infection but only to reduce bacterial 
colonization within the fabric.  
o The polyurethane foam bolster that covers the interface layer has a pore size of 400-600 
microns and a violet colorant; the foam manifolds negative pressure to the incision site.  
o A polyurethane film with acrylic adhesive provides adhesion of the dressing to the skin 
surrounding the incision. A polyurethane shell encapsulates the foam bolster and interface 
layer, providing a closed system.  
o The unit is battery powered for seven days, lightweight, easily portable and designed for single 
patient use.  
o The Prevena™ 45mL canister or the Prevena PLUS™ 150mL canister for collection of incision 
exudate. 
o Prevena Patch Strips, which may be used to help seal leaks around the dressing 
o All patient-contact materials are free of latex and DEHP [Di (2ethylhexl) phthalate].  
4.2. Provider Training on Use of NPWT Device 
All research staff and clinicians (labor & delivery and postpartum nurses, OR technicians, 
physicians) involved in the study will receive formal training on how to place and remove the 
prophylactic NPWT device.  
 Providers will have to demonstrate proficiency and receive certification by a KCI 
Representative in order to be part of the study 

 
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 Content of the training 
o Placement of the dressing over the wound 
 The dressing will be placed centrally over the wound to reduce the chance of 
wound fluid coming into contact with the port   
 Placement of the dressing so that the port should be uppermost from the wound 
and placed over intact skin   
 The dressing should be applied so that the border of the dressing is not creased. 
 Insertion of batteries into the pump 
 Connecting the pump to the dressing by twisting together the tubing connectors 
 Application of fixation strips around 4 sides of the dressing 
 Activation of the device to initiate negative pressure  
 Troubleshooting if negative pressure is not achieved 
 Inspection of dressing and indications for dressing change 
o Patients instructions on pump use  
 Disconnection of the pump for showering 
 Not to submerge dressing in water 
 Wiping the pump clean with a damp cloth using soapy water  
 When to notify the nurse or physician: all pump lights are off (pump is off), if amber 
light is flashing (indicating a leak), or if all lights are illuminated (indicating a pump 
failure) 
4.3. Screening  
Study personnel at each clinical site will screen and consent patients under the direction of the 
site PI.  Patients will be enrolled at the time of admission for delivery or anytime thereafter prior to 
cesarean.  Each center will have the flexibility to use an approach that is most efficient and suitable 
for their system to screen and consent patients. Medical records of all potential patients admitted for 

 
15 
 
 
 
 
 
 
 
 
 
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delivery will be reviewed and those who satisfy inclusion and exclusion criteria will be approached 
and written informed consent obtained.  A screening log will be used to track all patients approached 
for the study.   
 
 
4.4. Randomization 
Women will only be randomized once the decision is made to do a cesarean. A confidential 
web-based randomization sequence will be prepared by using blocks of variable sizes, stratified by 
study site, BMI category (30-39.9 and ≥40 kg/m2) and scheduled/non-labor versus unscheduled/labor 
cesareans. The randomization sequence will be maintained centrally by the study statistician. The 
patient’s group assignment will be revealed once basic information including confirmation of the 
inclusion criteria are submitted online. 
4.5. Procedures 
Schedule of Events 
  
Enrollment 
PP Day 2-7 or Day 
of Discharge 
1-2 weeks 
Postpartum 
Post-Op Day 30 
(+/- 2 days) 
4-6 weeks 
Postpartum 
Eligibility and Randomization 
X 
  
  
  
  
Interview: Maternal Demographic 
Characteristics 
X 
  
  
  
  
Skin Swabs/Adipose Tissue Biopsies 
X 
  
  
  
  
Chart abstraction: Prenatal Records 
  
X 
  
  
  
Chart abstraction: Fetal/Neonatal 
outcomes 
  
X 
  
  
  
Patient Satisfaction Survey 
  
X 
  
  
  
AE/SAE Form 
  
X 
X 
X 
X 
Chart abstraction: Outcome Assessment 
  
X 
X 
X 
X 
Phone Call/Follow Up Survey 
  
 X  
  
X 
  
Chart abstraction: Post Partum Form 
  
  
  
  
X 
 
Preoperative care 

 
16 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
Routine preoperative cesarean care at each center will be given to patients by their clinical 
providers.  These procedures are similar and all study sites have agreed on basic standardization of 
SSIs prevention strategies as well as diagnosis and treatment (Table 2). 
Standardized preoperative procedures include: 
 Clipping of hair at site of incision immediately prior cesarean as needed 
 Preoperative antibiotics within 60 minutes prior to incision.  Typical preoperative antibiotic used is 
2-3 g of cefazolin.  Penicillin-allergic patients will receive gentamicin and clindamycin.  Patients with 
chorioamnionitis will receive ampicillin, gentamicin, and clindamycin.   
 Skin preparation with chlorhexidine-alcohol or povidone-iodine solution with 3-minutes of drying time 
prior to draping. 
 Adherence to these procedures will be recorded and monitored. 
Intraoperative care 
 Choice of incision will be left to the surgeon.  The typical incision for a cesarean is a Pfannenstiel 
(low transverse) skin incision, although body habitus (particularly in obese women) and prior 
surgeries may dictate the use of a high transverse skin incision above the pannus or a vertical 
midline skin incision  
 The preferred uterine incision will be low transverse, unless intraoperative findings such as dense 
adhesions or poorly developed lower uterine segment necessitate a classical or high transverse 
incision 
 Closure of the subcutaneous layer if ≥2 cm 
 The preferred skin closure at the participating centers is subcuticular suture. However, type of 
incision, scar tissue, and patient preference may play a role in the decision to use staples 
 
 

 
17 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
Table 2: Routine infection prevention practices at each study site 
 
 
Washington 
University in 
St. Louis 
 
University of 
Alabama at 
Birmingham 
 
Ochsner 
Medical Center 
 
Mercy Hospital 
in St. Louis 
 
Indiana 
University 
Hair clipping 
Clipping 
immediate 
preop if needed 
Clipping 
immediate preop 
if needed 
Clipping 
immediate preop 
if needed 
Clipping 
immediate 
preop if needed 
Clipping 
immediate 
preop if needed 
Skin Prep 
Chlorhexidine-
alcohol; iodine-
alcohol if 
allergic to 
chlorhexidine 
Povidone-Iodine 
+ Chlorhexidine-
alcohol; 
chlorhexidine 
gluconate alone 
for urgent cases 
Chlorhexidine for 
non-urgent 
cases; betadine 
for urgent 
Betadine-
alcohol, 
chlorhexidine-
alcohol for 
betadine allergy 
Chlorhexidine-
alcohol for non-
urgent cases; 
betadine for 
urgent 
Antibiotics 
Administer 
Preoperatively 
Cefazolin: 2g if 
>80kg, 3 g for 
>160 kg. If 
laboring 
Azithromycin is 
added. If 
cephalosporin 
allergy: 
gentamicin 2 
mg/kg + 900 mg 
clindamycin. 
Administer 
Preoperatively 
Cefazolin: 2g if 
>80kg, 3 g for 
>160 kg. If 
laboring 
Azithromycin is 
added. If 
cephalosporin 
allergy: 
gentamicin 2 
mg/kg + 900 mg 
clindamycin 
Administer 
Preoperatively 
Cefazolin: 2g if 
>80kg, 3 g for 
>160 kg. If 
laboring 
Azithromycin is 
added. If 
cephalosporin 
allergy: 
gentamicin 2 
mg/kg + 900 mg 
clindamycin 
Administer 
Preoperatively 
Cefazolin: 2g if 
>80kg, 3 g for 
>160 kg. If 
laboring 
Azithromycin is 
added. If 
cephalosporin 
allergy: 
gentamicin 2 
mg/kg + 900 mg 
clindamycin 
Administer 
Preoperatively 
Cefazolin: 2g if 
>80kg, 3 g for 
>160 kg. If 
laboring 
Azithromycin is 
added. If 
cephalosporin 
allergy: 
gentamicin 2 
mg/kg + 900 mg 
clindamycin 
Delivery 
of 
placenta 
Spontaneous 
Spontaneous 
Manual 
Spontaneous 
Spontaneous 
Subcutaneous 
layer 
Closure if >2cm 
Closure if >2cm 
Closure if >2cm 
Closure if >2cm 
Closure if >2cm 
Skin closure 
Subcuticular 
suture 
Subcuticular 
suture 
Most 
subcuticular 
suture; rare 
staples 
Most 
subcuticular 
suture; rare 
staples 
Most 
subcuticular 
suture; rare 
staples 

 
18 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
Standard wound 
dressing 
Honeycomb 
dressing stays 
in place for 24 
hours 
Honeycomb 
dressing stays in 
place for 48 
hours 
Abdominal 
pressure 
dressing x24 
hours 
Abdominal 
pressure 
dressing x24 
hours 
Abdominal 
pressure 
dressing x 24 
hours 
 
 As this is a large pragmatic trial, and many factors play a role in operative decisions, the operative 
procedures used will be recorded and the impact of these variations on the effectiveness of 
prophylactic NPWT will be assessed in secondary analyses.  
Postoperative care 
 Patients will be monitored daily while in the hospital 
 Removal of standard surgical dressing at approximately 24 hours in patients randomized to 
standard dressing 
 We will plan to remove the negative pressure wound therapy dressing on postoperative day #4 or 
day of discharge in patients randomized to prophylactic NPWT with PrevenaTM /Prevena PLUSTM. 
However, patients who remain hospitalized will have the device on for up to 7 days. Therefore, the 
minimum duration of therapy will be 2-4 days with an anticipated average of duration of 
approximately 5 days. 
 Replacement of any dressing that is saturated  
 If a patient develops infection with the NPWT device in place the device will be removed and the 
patient given standard SSI therapy as outlined below 
 Patients will be educated about the signs and symptoms of infection and other study outcomes 
and encouraged to call their provider  
 Research staff will monitor subjects’ inpatient course for signs and symptoms of SSI 
 Management of surgical site infections will follow the Practice Guidelines of the Infectious 
Diseases Society of America56 
 All patients will sign a medical record release which will be faxed to any hospitals or physician’s 
office to obtain records for review 

 
19 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
 All clinical sites will follow policies to routinely send specimens for culture and sensitivity from all 
accessible infections such as wound/skin infections or drained abscesses in order to identify 
individual infectious agents and their antibiotic susceptibilities.  Outcomes pertaining to microbial 
resistance will be obtained through subject chart abstraction. 
The following infant data will be collected after delivery: Gender, weight, well baby, special care 
nursery or NICU, APGAR scores, umbilical cord blood gas results, neonatal outcomes and any 
complications will be collected. 
 
Figure 2: Algorithm for the management and treatment of surgical site infections (SSIs)56 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient with Wound Complaints 
(e.g., Pain, drainage, swelling, fever) 
No signs of infection 
Open wound 
Temp < 38 oC 
WBC <12 000 
Erythema <5 cm 
Physical Exam 
Signs of infection 
(e.g., erythema, swelling, purulent 
drainage) 
Seek other source 
Temp > 38 oC 
WBC >12 000 
Erythema >5 cm 

 
20 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
 
 
 
 
*Choice of antibiotics will be based on infection severity and local bacteria resistance patterns by the 
subject’s clinical care provider. 
 
4.6. Follow Up 
 We will use active surveillance by research staff to ascertain surgical site infections.   
 Research staff will follow-up with the research participant on the day of discharge or within 48 
hours (postpartum day 2-7) to assess for adverse events, assess the participant’s pain and 
obtain their satisfaction with their dressing. 
 Research staff will call subjects on approximately postoperative day 30 (±2 days).  They will ask 
the patient standardized questions regarding wound complications.  If the patient reports a 
hospital, clinic, or ER visit not associated with the study centers, the staff will obtain the name of 
the medical facility and request the records.  
 The EQ-5D-3L quality of life questionnaire will be administered at the 30-day call. 
 Typically, patients will have routine follow-up with their provider scheduled at 1-2 weeks and 4-
6 weeks post-partum.  
 We will obtain medical records from each of those clinic visits as well as records of unscheduled 
visits (to any hospital clinic or ER) to ascertain study outcomes  
4.7. Withdrawals 
Patients who withdraw from the study after randomization will be excluded from further follow-
up.  However outcomes ascertained up until the time of withdrawal will be reported in the intent-to-treat 
analysis. 
4.8. Outcome Measures 
4.8.1 Primary Outcome 
Dressing changes 
No antibiotics 
Dressing changes 
Antibiotics* 

 
21 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
Superficial or deep surgical site infections as defined according to the CDC’s National 
Healthcare Safety Network criteria. Diagnosis will be made by the treating physician and reviewed 
and validated centrally by the PI against the CDC’s National Healthcare Safety Network Definitions of 
Surgical Site Infections and blinded to intervention group 
A superficial incisional (or wound) SSI must meet the following criteria: Infection occurs within 
30 days after the operative procedure AND involves only skin and subcutaneous tissue of the incision 
AND patient has at least one of the following: i) purulent drainage from the superficial incision; ii) 
organisms isolated from an aseptically obtained culture of fluid or tissue from the superficial incision; 
iii) at least one of the following signs or symptoms of infection: pain or tenderness, localized swelling, 
redness, or heat, and superficial incision is deliberately opened by surgeon, and is culture-positive or 
not cultured (a culture-negative finding does not meet this criterion); iv) diagnosis of superficial 
incisional SSI by the surgeon or attending physician.  
A deep incisional (or wound) SSI must meet the following criteria: Infection occurs within 30 
days after the operative procedure AND involves deep soft tissues (e.g., fascial and muscle layers) of 
the incision AND patient has at least one of the following: i) purulent drainage from the deep incision 
but not from the organ/space component of the surgical site; ii) a deep incision spontaneously dehisces 
or is deliberately opened by a surgeon and is culture-positive or not cultured when the patient has at 
least one of the following signs or symptoms: fever (>38°C), or localized pain or tenderness (a culture-
negative finding does not meet this criterion); iii) an abscess or other evidence of infection involving the 
deep incision is found on direct examination, during reoperation, or by histopathologic or radiologic 
examination; iv) diagnosis of a deep incisional SSI by a surgeon or attending physician.  
4.8.2. Secondary Outcomes 
 Individual components of the primary outcome (superficial or deep SSI) 
 Organ space SSI (endometritis) 
 Other individual wound complications: dehiscence ≥2 cm, hematoma, seroma, erythema 

 
22 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
 Composite of any wound complications 
 Patient pain and satisfaction scores at discharge and postoperative day 30 
 Patient satisfaction with aesthetic appearance (scale of 0 - 10) at postoperative day 30 
 Healthcare resource utilization: physician office or ED visits, antibiotics for SSI, hospital readmission for 
SSIs, home health for SSI, wound clinic for SSI 
 Adverse events: skin blistering, allergic reaction, wound bleeding  
4.8.3. Cost-effectiveness analysis outcomes 
 Incremental cost per SSI prevented 
 Incremental cost per QALY 

 
23 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
Figure 3: Summary of Study Flow and Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient Admitted for Delivery 
Research Staff Screen and Consent Eligible Subjects 
Clinical Decision to Perform Cesarean Delivery 
Randomization 
 
Standard Dressing 
 
Prophylactic NPWT 
Inpatient and Outpatient Surveillance  
Data Collection by Research Staff
Data Management 
Interim and Final Data Analysis 
Standard Infection Prevention Measures  
(Skin antisepsis, weight-adjusted preoperative antibiotics) 

 
24 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
5. 
Data Management  
5.1. Data Collection 
We will collect detailed antepartum, intrapartum, and postpartum information from study 
participants into a comprehensive database.  
 Trained research staff in obstetric and perinatal outcomes abstraction at each center will be responsible 
for all research data abstraction from patient records   
 Research staff will undergo centralized specific training to ascertain study outcomes 
 Standardized information will be abstracted from all charts regardless of study group 
 Relevant data will be collected initially to assess eligibility. Complete baseline, outcome, wound culture, 
and cost data will be collected via direct interview and chart review 
 Several data collection forms will be used during these processes, including forms for maternal baseline 
data, preoperative and intraoperative care, maternal outcomes, postpartum clinic/hospital outcomes, 
and Quality of Life Questionnaire (EQ-5D-3L) 
 Data on these forms devoid of personal identifiers will be securely sent to the data management center 
through web-based entry 
5.2. Specimen collection and storage for future studies 
 Subjects will be asked to participate in an optional biospecimen collection in which their 
samples will be stored for batched analysis. These samples may be used for future research 
studies or shared with other researchers. These samples may include:  
o Skin swabs at the incision site before skin prep  
o Skin swabs at the incision site after skin prep 
o Subcutaneous adipose tissue biopsy prior to fascial incision 
o Subcutaneous adipose tissue biopsy after fascial closure 
 All specimens will be processed per the Manual of Operations and stored at -80 degrees Celsius 
+/-2 degrees until analysis 

 
25 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
5.3. Data Processing 
The Data Management Center (DMC) at Washington University School of Medicine will be 
responsible for data management and analysis in accordance with the analysis plan to be finalized by 
the steering committee and approved by the DSMB.  The Data Management Team based at 
Washington University includes an experienced statistician and a database manager.  Each site PI 
and nurse coordinator will be responsible for liaison with the DMC including transmitting de-identified 
abstracted information contained in the data collection forms.  Data management at each site will 
include: procedures for data entry, data editing, and compilation; procedures for data transmittal; and 
procedures for quality control, data verification, confidentiality and security.  Data will be collected and 
managed with REDCap (Research Electronic Data Capture), an established, secure, web-based data 
capture and management tool developed at Vanderbilt University and supported by the bioinformatics 
team at WUSM (http://www.biostat.wustl.edu/redcap/).  The security of the database will be 
maintained by the use of dedicated password protected encrypted computers with multiple private 
backups (daily, weekly, and monthly including on- and off-site storage for protection against disaster).   
5.4. Loss to follow-up and missing data 
We will employ strategies we have used in prior studies to achieve excellent follow-up and 
minimal missing data. Because patients will require necessary postoperative and postpartum visits, 
there will be ample opportunity for follow-up. In addition, we will obtain two contact numbers from 
subjects when available and contact them on approximately postoperative day 30 (±2 days). We will 
also obtain written authorization to obtain records from their Emergency Room and physician office 
visits and hospital readmissions. We will employ active data management at each site, including 
monthly data review for rates and patterns of missing data. Remedial measures including re-
abstraction of data and retraining of staff will be used as needed to minimize missing data. If data are 
still missing, we will address the deficiency analytically57. We will first determine if data is missing at 

 
26 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
random. We will then employ methods including multiple imputations and sensitivity analyses to test 
the robustness of our results. 
6. Data Analysis 
6.1. Sample Size and Power 
6.1.1. Primary Aim – Effectiveness 
The total sample size for the trial is estimated based on the primary outcome. We then 
estimate, on the basis of the sample size for the primary aim, the power we will have to detect 
clinically significant differences in the secondary aims. All sample size and power estimates are 
based on two-tailed tests, enabling us to detect an increase or decrease in rates of outcomes with 
use of prophylactic NPWT.  
The baseline rate of SSIs in obese women from our preliminary data is 11.6%. Furthermore, 
rates of SSIs at the study sites in all women 
range from 6 to 12% and are expected to be 
higher in obese women. Assuming a 
conservative baseline rate of 10%, we estimate 
that a total of 2850 subjects (1425 NPWT and 
1425 standard care) will be sufficient to detect 
a 30% relative difference in SSIs, with 80% 
power and 5% significance level and 
accommodation of 5% loss to follow-up (Table 4). This 30% difference represents the difference 
between a 10% rate of SSI in the standard care group and a 7% rate in the NPWT group. 
6.1.2. Secondary Aim 1 - Safety 
The sample size of 2,850 subjects for the primary aim will be sufficient to detect at least a 25% 
difference in composite adverse events between the two groups with 85% power and significance 
Table 4: Sample size estimation 
       (Power=80%, 2-tailed, α =0.05) 
 
 
Detectable 
relative difference 
Anticipated 
SSI rate with 
NPWT 
(assuming 
10% baseline 
rate) 
 
Sample size 
(assuming 5% 
loss to follow-
up) 
50% 
5.0% 
910 
40% 
6.0% 
1514 
33% 
6.7% 
2316 
30% 
7.0% 
2850 
25% 
7.5% 
4215 
20% 
8.0% 
6760 

 
27 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
level of 5%.  This represents the difference between a 16% rate of composite adverse events with 
NPWT (based on preliminary data58) and 12% with standard dressing. 
 
 
6.1.3. Secondary Aim 2 – Cost Effectiveness 
A recent cost-effectiveness analysis estimated a 400 to 600 patients as the adequate sample 
size of a future trial investigating cost- effectiveness of prophylactic NPWT at cesarean53. Thus, our 
sample size of 2850 for the primary outcome will provide sufficient power for the cost-effectiveness 
analysis. 
6.2. Data Analysis Plan 
6.2.1. Primary Analyses 
 Data analyses will adhere closely to the CONSORT guidelines55. Analyses will follow the 
intention-to-treat principle in which subjects will be analyzed in the group to which they were 
randomized, regardless of whether or not they received the assigned intervention. 
 Descriptive statistics will characterize the group of individuals recruited and investigate 
comparability of the two groups at baseline. Formal statistical testing will be limited to selected 
baseline characteristics considered to be prognostic factors for the primary outcome such as 
emergent cesarean, type of skin incision, and prolonged rupture of membranes. The categorical 
prognostic factors will be compared between trial groups by using the Chi-squared or Fisher’s exact 
tests as appropriate. The two-group independent t-test and Mann-Whitney U test will be used to 
compare normal and non-normally distributed continuous variables, respectively. The primary 
outcome and other categorical secondary outcomes will be compared between intervention groups by 
using the Cochran-Mantel-Haenszel test. We will calculate common relative risks and 95% 
confidence intervals associated with the primary and secondary outcomes.  

 
28 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
We will use the Breslow-Day test to assess homogeneity of the effect across subgroups (study 
sites, BMI category [30 – 39.9, ≥40], and scheduled/non-labor or unscheduled/labor cesareans, skin 
incision type [low transverse, high transverse, midline vertical], diabetes status). We will also conduct 
time-to-event analyses by using Kaplan Meier and Cox regression models to examine the pattern of 
SSIs in the two groups.  
 
6.2.2. Secondary Analyses 
Adjusted estimates 
 We will perform analyses aimed at obtaining estimates of treatment effectiveness, adjusting 
for any imbalances in baseline subject characteristics between groups. The objectives of these 
analyses are to estimate the influence of covariates on the outcome and to use them to improve the 
estimated difference between treatment groups. Logistic regression models will be used to identify 
and estimate the effect of multiple prognostic factors on the probability of SSI and other categorical 
outcomes.   
Cost-Effectiveness Analysis 
The economic analysis will be led by Aaron Caughey, MD, MPP, MPH, PhD, an MFM 
Specialist and Health Economist with extensive experience in cost-effectiveness analysis. We will 
adhere closely to the guidelines for economic analysis accompanying clinical trials set forth by the 
international Task Force on Good Research Practices on RCT Cost-Effectiveness Analysis59,60. The 
primary perspective of this economic evaluation will be societal, but we will also examine the patient 
and health care payer perspectives. This analysis will follow the intention-to-treat principle. The time 
horizon for the analysis will be the 30-day follow-up period of the trial, but we will include costs for 
treatment of SSIs beyond 30 days. Costs and effects will not be discounted because the time horizon 
for the analysis is short.  

 
29 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
Costs: Direct medical costs will be the primary measure, but indirect costs may be considered if 
feasible. Direct medical costs will include the cost of implementing prophylactic NPWT or standard 
dressing (e.g., device or dressing cost, treatment of side effects), and medical care for SSI (e.g., 
hospital costs, emergency room, outpatient services, wound care supplies, and medications). Indirect 
costs will include cost of traveling for outpatient visits and lost productivity from being absent from 
work or usual activity. Secondary data sources will be used as much as possible to reduce the burden 
of data collection for economic analysis. Unit costs for inpatient and outpatient services, outpatient 
procedures, laboratory tests, and office visits will be estimated by using charges adjusted for cost-to-
charge ratios. The unit cost of medications will be derived from average wholesale prices. Unit costs 
for study patients’ time will be based on the average national wage rate. 
Effectiveness: The effectiveness measures will be rate of SSI and QALYs. We will calculate QALYs 
by applying utility weights (1=perfect health, 0=death) to various health states values derived from the 
EuroQol five dimensions questionnaire (EQ-5D). The EQ-5D is a standardized instrument for 
measuring generic health status. The health status measured with EQ-5D-3L is used for estimating 
preference weight for that health status, then by combining the weight with time, QALYs can be 
computed. We will administer the EQ-5D to patients at the 30-day follow-up phone call. Once the data 
have been collected a scoring function can be used to assign a value (i.e., EQ-5D™ index score) to 
self-reported health states from a set of U.S.-generated value set (preference weights)61. 
EQ-5D is one of the most commonly used generic health status measurement, and its good 
validity and reliability have been reported in various health conditions. The EQ-5D-3L questionnaire is 
made up for two components; health state description and evaluation. In the description part, health 
status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression. Mobility dimension asks about the person's walking ability. 
Self-care dimension asks about the ability to wash or dress by oneself, and usual activities dimension 
measures performance in "work, study, housework, family or leisure activities". In the pain/discomfort 

 
30 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
dimension, it asks how much pain or discomfort they have, and in the anxiety/depression dimension, 
it asks how anxious or depressed they are. The respondents self-rate their level of severity for each 
dimension using a three-level (3L) scale: having no problems, having some or moderate problems, 
being unable to do/having extreme problems. In the evaluation part, the respondents evaluate their 
overall health status using the visual analogue scale (EQ-VAS) which ranges from 0 (the worst health 
you can imagine) to 100 (the best imaginable health state). 
Cost-effectiveness: The measures of cost-effectiveness of prophylactic NPWT will be incremental 
cost per case of SSI prevented and incremental cost per QALY. They will be calculated as follows. 
 
Incremental cost per case of SSI prevented: 
(Mean CostProphylactic NPWT - Mean Coststandard care) ÷ (Mean SSI RateProphylactic NPWT - Mean SSI Ratestandard care) 
 
Incremental cost per QALY: 
 
 (Mean CostProphylactic NPWT - Mean Coststandard care) ÷ (Mean QALYProphylactic NPWT - Mean QALYstandard care)  
 
 
All estimates of costs, outcomes, and cost-effectiveness will be reported as means with 95% 
confidence intervals. In accordance with the current threshold used in the U.S., prophylactic NPWT 
will be considered cost-effective if the incremental cost per QALY is less than $100,00062. We will 
conduct sensitivity analysis to evaluate uncertainty of the results by varying probability (e.g., baseline 
rate of SSI, magnitude of risk reduction) and cost parameters (e.g., cost of the NPWT device, 
healthcare cost). We will employ Monte Carlo simulation to assess the robustness of our findings by 
simultaneously sampling distributions of multiple parameters within the model. 
Etiology, timing, and risk factors of SSIs in obese women 
 For these analyses, the two study groups (NPWT and standard care) will be combined into a 
cohort, and all analyses will adjust for group assignment and study site. We will evaluate wound 
culture data to determine the types and frequency of different bacteria including MRSA. We will use 
time-to-event analyses to estimate median time to SSIs and time to heal. We will identify risk factors 

 
31 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
for SSI initially based on factors associated with SSI in bivariate analysis (at P<0.1 threshold), 
biological plausibility, and factors reported in the literature2,63-68. We will use backwards elimination to 
reduce the number of variables in the model. Variables that are significant will be retained as risk 
factors for SSIs in obese women. Fit for the final model will be assessed by using the Hosmer-
Lemeshow goodness-of-fit test69.  
Other planned secondary analysis 
 Effect of prophylactic negative pressure wound therapy on a composite of any wound complication 
 Effect of prophylactic negative pressure wound therapy on rate and type of wound cultures 
 Effect of prophylactic negative pressure wound therapy on healthcare resource utilization 
 Association between levels of cefazolin in the subcutaneous layer before fascial incision and after 
fascial closure and risk of surgical site infection 
 Risk of surgical site infection and other wound complications with different skin incision types 
 Relationship between skin microbiome at the incision site and risk of surgical site infection 
 Subcuticular suture type and risk of surgical site infection 
 Timing of removal of standard dressing and surgical site infection 
 
 

 
32 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
 
7. Safety monitoring 
The interventions compared in this trial are both currently used in clinical obstetric practice. 
Further, the adverse events reported with use of prophylactic NPWT at cesarean were minor and 
their frequency was comparable to rates with standard dressing51. Therefore, no serious or life-
threatening adverse events are expected in this trial. Nonetheless, the following measures will be 
taken to monitor and investigate adverse events: 
 
7.1. Independent Data and Safety Monitoring Board (DSMB) 
  
An independent study-specific DSMB will be composed of three distinguished individuals 
(Sindhu Srinivas, MD, MSCE; Alison Cahill, MD, MSCI; and Jenifer Allsworth, PhD) who represent 
appropriate expertise in epidemiology, obstetrics, clinical trials, and biostatistics. They will provide 
oversight to assure that the trial accrues at a sufficient rate and that the safety and privacy of all study 
participants is assured. The DSMB will hold conference calls every six months to review study 
progress and monitor adverse events.  
 
7.2. Adverse events reporting 
Reportable Events 
Each site-PI will oversee the safety of the study at his/her site. During the study, the investigator or 
study site personnel will be responsible for querying and recording adverse events (AEs) and serious 
adverse events (SAEs), as detailed below.  
 
 
 

 
33 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
Types of Reportable Events: 
Serious Adverse Events (SAE) 
The site must report all SAEs to the lead site, whether or not they result from study participation, 
within 24 hours of learning of the event. A serious adverse event (SAE) is any adverse event 
occurring within the timelines specified in the protocol that results in any of the following outcomes:  
● Death 
● Life-threatening situations (subject is at immediate risk of death)  
o Postpartum hysterectomy for infection control 
o Maternal sepsis 
o Necrotizing fasciitis 
o Maternal ICU admission 
Adverse Events (AE)  
An adverse event is any untoward medical occurrence in a clinical investigation subject administered 
an investigational product and which does not necessarily have to have a causal relationship with this 
treatment. An AE can, therefore, be any unfavorable and unintended sign (that could include a 
clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a medicinal product, whether or not considered related to the medicinal product.  
For this study, abnormal laboratory findings (e.g., clinical chemistry, hematology) or other abnormal 
assessments (e.g., electrocardiogram, X-rays, vital signs) per se are not reported as AEs.  Only the 
Adverse Events of Special Interest (AESI) defined below will be recorded on the CRFs and in the 
subject’s chart.   
 
 
 

 
34 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
Adverse Events of Specific Interest (AESI) 
Adverse events of particular clinical importance (other than SAEs mentioned above) will be classified 
as adverse events of specific interest (AESIs). For this study, AESIs refer to:  
 Mild/moderate reactions:  
o Skin blisters 
o Wound bleeding 
o Allergic skin reaction 
Assessing and Documenting Reportable Events: 
Subjects will be evaluated for adverse events in the following manner: 
• 
Routine monitoring by physicians, nurses and research team during inpatient stay, with 
data obtained from the subject’s EMR by research staff.   
• 
Typically patients will be scheduled for routine follow-up with their provider at 1-2 weeks 
and 4-6 weeks postpartum 
• 
Research staff will call subjects on postoperative day 30 (±2 days) and will ask patients 
standardized questions regarding wound complications.  Medical records will be obtained 
for any patient or provider-reported complications.  
An adverse event report will be generated for each event that will include the following: 
• 
Date of event discovery 
• 
Severity (mild, moderate, severe, life threatening/disabling, death) 
• 
Relationship to treatment 
• 
Action taken 
• 
Outcome 
• 
Expected or unexpected 
• 
Date reported  
• 
Relevant notes/chart records/supporting documentation to corroborate the event 
• 
To whom event was reported (IRB, Sponsor) 

 
35 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
o Non-Severe AESI will be reported to the lead site as aggregate every 6 
months, and to the IRB at renewal.  
o SAEs will be reported within 24 hours of discovery to the IRB and the 
lead site. 
 
 
 

 
36 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
Relationship of Reportable Events: 
An Investigator must make the determination of relationship to the drug for each SAE and/or AESI. 
The relationship to the drug or device should be assessed using the guidelines presented in the table 
below.  
Relationship to 
Device 
Description  
Related  
● Previously known harmfulness of device; or 
● Follows a reasonable temporal sequence from administration of the 
device; or  
● Follows a known or expected response pattern to the suspected 
intervention; or 
● Is confirmed by stopping or discontinuing the device; and  
● That is not explained by any other reasonable hypothesis  
Probably related  
• Follows a reasonable temporal sequence from the time of study 
intervention; and/or  
• Follows a known response pattern to the study device; and  
• Was unlikely to have been produced by other factors such as the 
subject’s clinical state, therapeutic intervention, or concomitant therapy  
Possibly related  
• Follows a reasonable temporal sequence from the time of study 
intervention; and/or  
• Follows a known response pattern to the study device; but  
• Could have been produced by other factors such as the subject’s 
clinical state, therapeutic intervention, or concomitant therapy  
Unlikely related  
• Does not follow a reasonable temporal sequence from the time of study 
intervention; and  
• Was likely produced by other factors such as the subject’s clinical state, 
therapeutic intervention, or concomitant therapy but for which 
relationship cannot be definitely ruled out  
Not related  
The adverse event can be determined with certainty to have no 
relationship to the study device 
 

 
37 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
 
Severity of Reportable Events:  
The investigator will assess the severity of the AE using the following general guidelines:  
Severity 
Description 
Mild: 
An AE that is usually transient, requiring no special treatment, and 
does not interfere with the subject’s daily activities.  
Moderate: 
An AE that introduces a low level of inconvenience or concern to the 
subject and may interfere with daily activities but is usually 
ameliorated by simple therapeutic measures.  
Severe: 
An AE that interrupts a subject’s usually daily activity and typically 
requires systemic drug therapy or other treatment (a severe AE may 
not necessarily qualify as an SAE).  
Life-threatening: 
An AE that put the subject at immediate risk of death from the event 
as it occurred. This does not include an event that might have led to 
death if it had occurred with greater severity.  
 
 
 
 

 
38 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
Outcomes of Reportable Events: 
The investigator will categorize the outcome of each reportable event according to the definitions 
below:  
Status 
Description 
Resolved: 
The subject recovered from the SAE or AESI.  
Resolved with 
sequelae: 
A condition whereby the consequences of a disease or injury include 
lingering effects.  
Ongoing: 
At the time of the last assessment, the event is ongoing, with an 
undetermined outcome. Note: Ongoing SAEs and AESIs are not 
considered resolved as a result of death and no SAE or AESI stop 
date should be recorded for an AESI that is ongoing at the time of 
death.  
Fatal: 
Adverse Event directly caused death. If a subject dies during 
participation in the study the lead site should be provided with a copy 
of any post-mortem findings. Note: Death is an outcome of an 
adverse event and not an adverse event in itself. All reports of subject 
death should include an adverse event term (other than “Death”) for 
the cause of the death.  
 
 
 

 
39 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
Data Monitoring and Quality Control 
Periodic monitoring visits will be made at the investigational site throughout the clinical study to 
ensure that the investigator obligations are fulfilled, and all applicable regulations and guidelines are 
being followed. These visits will ensure that the facilities remain acceptable, the investigational plan is 
being followed, the IRB and local authorities have been notified of approved investigational plan 
changes as required, complete records are being maintained, appropriate and timely reports have 
been made to the sponsor and/or its designees and the IRB, and the investigator is carrying out all 
agreed upon activities.  
An annual report will be generated beginning one year after the first enrollment and will include the 
following: 
• 
A list and summary of adverse events;  
• 
Whether adverse event rates are consistent with pre-study assumptions;  
• 
A summary of recruitment and retention and reason for dropouts;  
• 
Whether the study is on track to be completed and accomplish the stated aims. 
 
Confidentiality: 
Information about study subjects will be kept confidential and managed according to the requirements 
of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). Those regulations require 
a signed subject authorization informing the subject of the following:  
• What protected health information (PHI) will be collected from subjects in this study  
• Who will have access to that information and why  
• Who will use or disclose that information  
• The rights of a research subject to revoke their authorization for use of their PHI  
 

 
40 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
In the event that a subject revokes authorization to collect or use PHI, the investigators, by regulation, 
retains the ability to use all information collected prior to the revocation of subject authorization. For 
subjects that have revoked authorization to collect or use PHI, attempts should be made to obtain 
permission to collect at least vital status (i.e. that the subject is alive) at the end of their scheduled 
study period. 
Data Collection and Management  
Case Report Forms— 
Qualified study staff at the investigational site will perform primary data collection. Electronic case 
report forms (eCRFs) will be used to collect all subject data during the study. The investigator is 
responsible for the accuracy and completeness of all data on the eCRFs. Lead site personnel will 
review completed eCRFs at regular intervals throughout the study.  
Information on the eCRFs will be compared to information originally recorded on source documents 
related to the study. Information on the eCRF must match the same information on the source 
documents or a data query will be issued. All eCRFs will be reviewed for completeness, validity, and 
consistency. Queries will be generated and resolved with the sites and all protocol deviations will be 
recorded on the eCRF.  
Source data— 
Source data is all information, original records of clinical findings, observations, or other activities in a 
clinical trial necessary for the reconstruction and evaluation of the trial. Source data are contained in 
source documents. Examples of these original documents, and data records include: hospital 
records, clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation 
checklists, pharmacy dispensing records, recorded data from automated instruments, copies or 
transcriptions certified after verification as being accurate and complete, microfiches, photographic 

 
41 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the 
laboratories, and at medico-technical departments involved in the clinical trial. 
7.3. Interim analyses 
We anticipate two interim analyses after 50% and 75% of the sample size are recruited, but 
the exact timing will be at the discretion of the DSMB. Analyses will be performed by the study 
statistician and presented to the DSMB, which will make recommendations regarding further conduct 
of the trial. At their first meeting, the DSMB will establish thresholds and rules for trial stoppage based 
on safety and efficacy limits. Although early stopping decisions cannot be based purely on a 
mathematical stopping rule, we will use the Haybittle-Peto stopping rule as a guide70,71. Under this 
rule, the interim analyses of the primary outcome would have to demonstrate an extreme difference 
between groups (P <0.001) to justify stopping early for efficacy. This rule has the advantages that the 
exact number of interim analyses need not be specified in advance and the overall type I error is 
preserved at 0.05; therefore, sample size adjustment for multiple testing is not needed.  
 
 

 
42 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
8. Study Administration 
As a multicenter trial with experienced collaborating investigators, governance will be shared rather 
than directed by a highly centralized and hierarchal structure. The Coordinating Center will be located 
at Indiana University and the Data Management Center will be located at Washington University in St 
Louis. All the investigators will form the Steering Committee, chaired by the PI.  
         Figure 4: Trial administrative structure 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Coordinating Center/Lead Site, Indiana University, will be responsible for: 
 Maintaining the study protocol and making revisions 
 Updating the site operations manual as needed 
 Performing overall management and coordination of the intervention and measurements 
 Ensuring all Institutional Review Board requirements are up to date at all sites 
 Over-seeing and assisting with recruitment 
 Providing training and support for data instruments and quality assurance and control 
Data Management and 
Analysis Center  
Washington University 
(Statistician-Lu) 
Study Site 2             
Washington University 
In St. Louis, Missouri 
(Site PI- Macones) 
Coordinating Center  
Lead Site 
 Indiana University 
 (PI/PD-Tuuli) 
Steering 
Committee 
(Chair-Tuuli) 
Data Safety and 
Monitoring Board 
(Chair-Srinivas) 
Study Site 3             
University of Alabama 
at Birmingham 
(Site PI-Harper) 
 
PI/PD-Tuuli 
 
Study Site 4               
Ochsner Medical Center 
New Orleans, Louisiana 
(Site PI-Longo) 
Study Site 5 (Closed)       
Mercy Hospital 
St. Louis, Missouri 
(Site PI-Trudell) 

 
43 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
 Coordinating progress reports to the data management center at WashU 
The Data Management and Analysis Center, WashU, will be responsible for: 
 Creation of randomization sequence 
 Creation of the database and extraction tools 
 Data cleaning, outlier detection, and preparation for analysis 
 Primary analyses of interim data 
 Additional analyses as requested by the DSMB or Coordinating Center 
 Primary intention-to-treat analyses  
 Planned secondary analyses  
Participating Clinical Sites will be responsible for: 
 Screening and recruiting participants 
 Determining participant eligibility 
 Designating group assignment as specified by central randomization 
 Data entry 
 Developing site-internal procedures and training/certifying staff members as appropriate 
 Assuring compliance with Institutional Review Board requirements 
 Responding to Quality Assurance reports 
 Maintaining good recruitment rate 
 Reviewing and reconciling study data 
 Entering participant data into study database and responding to data cleaning requests 
 Submitting inquiries on procedural issues to the Coordinating Center 
 Responding to requests for data regarding interim and final analyses and data safety 
Steering Committee 
The Steering Committee (SC) for the trial will be chaired by The PI. The SC will comprise the PI (Dr 
Tuuli) and the site-PIs (Drs. Macones, Warren, Harper, and Longo) and Health Economist Co-I (Dr 
Caughey). The functions and responsibilities of the SC are: 

 
44 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
 Decision making regarding participant eligibility and study end points 
 Publication and presentation guidelines 
 Authorship determination 
 Consideration and approval of ancillary studies 
 Addressing scientific or operational matters as they arise 
The investigators are all experienced and most have collaborated in prior studies. Any issues will be 
addressed at regular Steering Committee conference calls and yearly scheduled meetings to coincide 
with the annual Society for Maternal Fetal Medicine meeting attended by most investigators. 
Data Safety and Monitoring Board (DSMB) 
A DSMB has been established to ensure objective oversight of the trial’s safety and conduct. 
Members of the Data Safety and Monitoring Board will be Sindhu Srinivas, MD, MSCE (Chair); Alison 
Cahill, MD, MSCI; and Jenifer Allsworth, PhD, who represent appropriate expertise including 
epidemiology, infectious disease, obstetrics, clinical trials, and biostatistics. Members are not involved 
in any aspect of the trial operation. They will provide oversight to assure that the trial accrues at a 
sufficient rate and that the safety and privacy of all study participants is assured. The DSMB will hold 
conference calls every six months to review study progress and monitor adverse events. The DSMB 
will be confidentially briefed by the study statistician before each meeting regarding study progress, 
and study outcomes.  That information will be available to the study investigators once disclosed by the 
DSMB.  The DSMB will issue a written report to the investigators after each meeting outlining any study 
issues and needed actions. 
 
 

 
45 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
9. Protection of Human Subjects 
Assessment of Risks 
Subject Characteristics 
All women admitted to the labor and delivery units of the participating medical centers will be 
screened against inclusion and exclusion criteria. Eligible subjects will be approached for written 
consent to participate in the study. Consent forms will be translated and back translated (primarily into 
Spanish, but others as necessary) for non-English speaking participants. The informed consent 
process for these participants will be conducted by an interpreter with the research staff present, or 
by research staff fluent in the subject’s native language. Consented subjects will be randomized once 
they are committed to cesarean delivery. We will use broad inclusion criteria to ensure generalizability 
of our results.   
Table 5: Inclusion and exclusion criteria 
Inclusion criteria (rationale) 
 Gestational age ≥23 weeks (gestational age at which cesarean deliveries are typically 
performed) 
 Prepregnancy BMI≥30 (Based on BMI at first prenatal visit; group of women at particularly high 
risk for both cesarean delivery and SSIs) 
 Planned or unplanned cesarean delivery (procedure in which NPWT is being tested) 
Exclusion criteria (rationale) 
 Unwillingness or unable to consent 
 Non-availability for postoperative follow-up (follow-up is needed to ascertain study outcomes) 
 Contraindication to NPWT applicable to women undergoing cesarean (device will not be used 
in patients with contraindications) 
o Pre-existing infection around incision site 
o Bleeding disorder 
o Therapeutic anticoagulation 
o Prior irradiated skin 
o Allergy to any component of the dressing (e.g. silicone, silver, adhesive tape) 
 

 
46 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
Potential Risks 
The potential risk to study subjects is expected to be minimal, but include the following: 
1. Loss of confidential health information. 
2. Skin blisters, allergic skin reactions, or wound bleeding. 
Adequacy of protection against risks 
Protection of Confidentiality 
Consent from patients will be obtained in a private setting, such as a quiet conference area or 
the patient’s private room. Data will be collected and managed with REDCap (Research Electronic 
Data Capture), an established, secure, web-based data capture and management tool developed at 
Vanderbilt University and supported by the bioinformatics team at Washington University School of 
Medicine (http://www.biostat.wustl.edu/redcap/). The REDCap application executes within the private 
zone of the WUBIOS Computing Resource within the Division of Biostatistics. This private zone is 
separated from the Internet and the general WUSTL network by a firewall. WUBIOS is a 
professionally managed, HIPAA compliant network which has been approved by the WUSM security 
officer. Access to REDCap is restricted to either computers which are located within WUBIOS or 
other WUSM secure networks or which have a WUBIOS issued digital certificate installed in the 
user's browser. Users of REDCap are required to sign a user agreement and be authorized by their 
supervisor. A user specific userID/password is required for logging into REDCap. For each research 
project, IRB approval is required and an administrator within the project grants specific users access 
rights to the project. Read or Read/Edit privileges are granted on a form-by-form basis for each user. 
Rights to download data are also controlled by the project administrator.  
As the data are entered into the electronic database, the database will be password protected. 
Only research staff of this project will have authorization to access the files, with permission 
controlled by the Data Manager; all other access will be prohibited. Access to the files will be logged 
electronically, and access will only be made for the purposes of conducting the study. 

 
47 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
All data collected for this study will be used for research purposes only. The data collected 
from the medical record will be limited to only what is necessary to carry out the study as outlined. No 
data from the study will be reported on an individual basis; all findings from this study will be reported 
in statistical summary form only. All members of the research team will treat all data with strict 
confidentiality. Each subject will be assigned a unique study code number that will be used on all data 
forms; patient names will not be abstracted. A list of patient names and study code numbers will be 
maintained separately from the data extraction forms, securely. Only the investigators and project 
staff, with the proper training on research practices including the protection of confidentiality, will have 
access to this information. The data extraction forms will also be kept in the aforementioned secure 
fashion, and only research team members will be granted access.  
 
Potential Benefits/Importance of knowledge gained 
The study is not designed to provide direct benefits to research participants. Nonetheless, if our 
hypothesis that obese women will have lower rates of SSIs after cesarean with use of prophylactic 
NPWT than with standard care is correct, then subjects randomized to NPWT will have the benefits 
lower rates of SSIs.  More importantly, results from this study have the potential to improve outcomes 
for obese women undergoing cesarean delivery. Because the anticipated risk to participants is 
minimal, the risks-benefit ratio is very favorable. 
 
 
 
 

 
48 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
10. Study Time Table 
The schedule of key activities over the 5-year project period is depicted in Table 5 below.   
Table 5: Study Timeline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Project Period (months) 
0-6 
6-12 
12-18 
18-24 
24-30 
36-42 
42-48 
48-54 
54-60  
Protocol development & IRB 
 
 
 
 
 
 
 
 
 
Staff recruitment and training 
 
 
 
 
 
 
 
 
 
Study forms and database  
 
 
 
 
 
 
 
 
 
Subject recruitment 
 
 
 
 
 
 
 
 
 
Data collection & 
management 
 
 
 
 
 
 
 
 
 
Data analysis 
 
 
 
 
 
 
 
 
 
Drafting of manuscript & 
reports  
 
 
 
 
 
 
 
 
 

 
49 
 
 
 
 
 
 
 
 
 
                     Version 1.9 August 29, 2019 
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