PICO Negative Pressure Wound Therapy in Obese Women Undergoing Elective Cesarean Delivery.
Phase: PHASE3
Conditions: Cesarean Section Complications, Cesarean Wound; Dehiscence, Cesarean Wound Disruption
Sponsor: Northwell Health

 
 
Clinical Trial Protocol  
NIH-FDA Clinical Trial Protocol Template 
a 

PICO Negative Pressure Wound Therapy in obese 
women undergoing elective cesarean delivery. 
IRB / Protocol Number: 17-0843 
National Clinical Trial (NCT) Identified Number:   NCT 03414762  
Principal Investigator:  Anar Yukhayev, MD 
IND/IDE Sponsor:  None 
Funded by: Department of Obstetrics and Gynecology 
Version Number:  v.2.1 
July 21, 2021 
 
Summary of Changes from Previous Version: 
Affected Section(s) 
Summary of Revisions Made 
Rationale 
2.3.1 
Updated PICO pump risk regarding magnet 
To be consistent with information 
in the patient brochure. 

  
NIH-FDA Clinical Trial Protocol Template 
ii 
Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
1 
PROTOCOL SUMMARY ............................................................................................................................... 1 
1.1 
Synopsis ................................................................................................................................................ 1 
1.2 
Schema ................................................................................................................................................. 4 
1.3 
Schedule of Activities (SoA) ............................................................................................................... 5 
2 
INTRODUCTION ............................................................................................................................................ 5 
2.1 
Study Rationale .................................................................................................................................... 5 
2.2 
Background........................................................................................................................................... 6 
2.3 
Risk/Benefit Assessment .................................................................................................................... 7 
2.3.1 
Known Potential Risks ..................................................................................................... 7 
2.3.2 
Known Potential Benefits ................................................................................................ 7 
2.3.3 
Assessment of Potential Risks and Benefits ................................................................ 8 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................................ 8 
4 
STUDY DESIGN ............................................................................................................................................. 9 
4.1 
Overall Design ...................................................................................................................................... 9 
4.2 
Scientific Rationale for Study Design.............................................................................................. 10 
4.3 
Justification for Dose ......................................................................................................................... 10 
4.4 
End of Study Definition ..................................................................................................................... 10 
5 
STUDY POPULATION ................................................................................................................................ 11 
5.1 
Inclusion Criteria ................................................................................................................................ 11 
5.2 
Exclusion Criteria ............................................................................................................................... 11 
5.3 
Lifestyle Considerations .................................................................................................................... 12 
5.4 
Screen Failures .................................................................................................................................. 12 
5.5 
Strategies for Recruitment and Retention ...................................................................................... 12 
6 
STUDY INTERVENTION ............................................................................................................................ 13 
6.1 
Study Intervention(s) Administration ............................................................................................... 13 
6.1.1 
Study Intervention Description ..................................................................................... 13 
6.1.2 
Dosing and Administration ............................................................................................ 13 
6.2 
Preparation/Handling/Storage/Accountability ................................................................................ 13 
6.2.1 
Acquisition and accountability ...................................................................................... 14 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ................................................ 14 
6.2.3 
Product Storage and Stability ....................................................................................... 15 
6.2.4 
Preparation ...................................................................................................................... 15 
6.3 
Measures to Minimize Bias: Randomization and Blinding ........................................................... 16 
6.4 
Study Intervention Compliance ........................................................................................................ 17 
6.5 
Concomitant Therapy ........................................................................................................................ 17 
6.5.1 
Rescue Medicine ............................................................................................................ 17 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL .................................................................................................................... 17 
7.1 
Discontinuation of Study Intervention ............................................................................................. 17 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................................................... 18 
7.3 
Lost to Follow-Up ............................................................................................................................... 18 
8 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................................... 18 
8.1 
Efficacy Assessments ....................................................................................................................... 19 
8.2 
Safety and Other Assessments ....................................................................................................... 19 
8.3 
Adverse Events and Serious Adverse Events ............................................................................... 20 

  
NIH-FDA Clinical Trial Protocol Template 
iii 
8.3.1 
Definition of Adverse Events (AE) ............................................................................... 20 
8.3.2 
Definition of Serious Adverse Events (SAE) .............................................................. 20 
8.3.3 
Classification of an Adverse Event .............................................................................. 21 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 22 
8.3.5 
Adverse Event Reporting .............................................................................................. 23 
8.3.6 
Serious Adverse Event Reporting ............................................................................... 23 
8.3.7 
Reporting Events to Participants ................................................................................. 23 
8.3.8 
Events of Special Interest ............................................................................................. 23 
8.3.9 
Reporting of Pregnancy ................................................................................................ 23 
8.4 
Unanticipated Problems .................................................................................................................... 23 
8.4.1 
Definition of Unanticipated Problems (UP) ................................................................. 23 
8.4.2 
Unanticipated Problem Reporting ................................................................................ 24 
8.4.3 
Reporting Unanticipated Problems to Participants ................................................... 25 
9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 25 
9.1 
Statistical Hypotheses ....................................................................................................................... 25 
9.2 
Sample Size Determination .............................................................................................................. 25 
9.3 
Populations for Analyses .................................................................................................................. 26 
9.4 
Statistical Analyses............................................................................................................................ 26 
9.4.1 
General Approach .......................................................................................................... 26 
9.4.2 
Analysis of the Primary Efficacy Endpoint(s) ............................................................. 27 
9.4.3 
Analysis of the Secondary Endpoint(s) ....................................................................... 28 
9.4.4 
Safety Analyses .............................................................................................................. 29 
9.4.5 
Baseline Descriptive Statistics ..................................................................................... 29 
9.4.6 
Planned Interim Analyses ............................................................................................. 29 
9.4.7 
Sub-Group Analyses ..................................................................................................... 29 
9.4.8 
Tabulation of Individual participant Data .................................................................... 29 
9.4.9 
Exploratory Analyses ..................................................................................................... 30 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 30 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................................... 30 
10.1.1 
Informed Consent Process ........................................................................................... 30 
10.1.2 
Study Discontinuation and Closure ............................................................................. 31 
10.1.3 
Confidentiality and Privacy ........................................................................................... 31 
10.1.4 
Future Use of Stored Specimens and Data ............................................................... 32 
10.1.5 
Key Roles and Study Governance .............................................................................. 32 
10.1.6 
Safety Oversight ............................................................................................................. 32 
10.1.7 
Clinical Monitoring .......................................................................................................... 32 
10.1.8 
Quality Assurance and Quality Control ....................................................................... 33 
10.1.9 
Data Handling and Record Keeping ............................................................................ 33 
10.1.10 
Protocol Deviations ........................................................................................................ 34 
10.1.11 
Publication and Data Sharing Policy ........................................................................... 34 
10.1.12 
Conflict of Interest Policy .............................................................................................. 35 
10.2 
Additional Considerations ................................................................................................................. 35 
10.3 
Abbreviations ...................................................................................................................................... 36 
10.4 
Protocol Amendment History ........................................................................................................... 38 
11 
REFERENCES ............................................................................................................................................. 40 
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
1 
STATEMENT OF COMPLIANCE 
The trial will be conducted in accordance with International Conference on Harmonisation Good Clinical 
Practice (ICH GCP) and the applicable United States (US) Code of Federal Regulations (CFR). The Principal 
Investigator will assure that no deviation from, or changes to the protocol will take place without 
documented approval from the Institutional Review Board (IRB), except where necessary to eliminate an 
immediate hazard(s) to the trial participants. All personnel involved in the conduct of this study have 
completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval.  Approval of both the protocol and the consent form must 
be obtained before any participant is enrolled.  Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study.  All changes to the consent form 
will be IRB approved; a determination will be made regarding whether a new consent needs to be 
obtained from participants who provided consent, using a previously approved consent form. 
1 
 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Title: 
Evaluation of the PICO Single Use Negative Pressure Wound Therapy 
(NPWT) in Obese Women Undergoing Elective Cesarean Delivery. 
 
Study Description: 
A randomized controlled, parallel group, superiority, open-label, single-
institution, Phase 3 interventional clinical trial to evaluate clinical 
outcomes in obese gravidas undergoing elective cesarean delivery whose 
wounds were dressed with the PICO Negative Pressure Wound Therapy 
(NPWT) versus the standard dressing. We hypothesize that the PICO NPWT 
will reduce the incidence of surgical site occurrences and interventions 
and postoperative readmissions in obese women. The study will compare 
surgical site occurrences and surgical incision intervention incidence within 
42 +/- 10 days post cesarean delivery in obese women who have the 
current standard-of-care dressing versus the PICO NPWT.  
 
Objectives: 
 
The purpose of this study is to compare short-term clinical outcomes 
among obese women undergoing cesarean delivery between those who 
received the post-surgical standard-of-care wound dressing versus the 
PICO negative pressure wound therapy system (NPWT).   
 
 
Primary Objective Measures:    
The incidence of postoperative Surgical Site Occurrences (SSOs) up to Day 
42 (+/- 10 Days) post Cesarean delivery.  
SSOs include:  
Unanticipated local inflammatory response 
Prolonged drainage 
Fluid collection 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
2 
Dehiscence 
Surgical site infection (SSI) 
 
 
Secondary Objective Measures:  
 
Incidence Rate of Surgical Incision Intervention (SII) up to Day 42 (+/- 10 
Days) Post Cesarean delivery.  
 
Interventions include: 
Antimicrobials for surgical site infection 
Surgical drainage of the incision 
Surgical incision packing 
Adjunctive negative pressure therapy 
Debridement 
Re-operation 
 
Endpoints: 
Primary Endpoint: confirmed SSO within 42 (+/- 10 Days) post Cesarean 
delivery.  
Secondary Endpoint: confirmed SII within 42 (+/- 10 Days) post Cesarean 
delivery.  
 
Study Population: 
Samples size of 396 females aged ≥ 18 years who are able to provide 
consent and are undergoing a planned cesarean delivery using 
subcuticular skin closure technique at the Long Island Jewish Medical 
Center. Inclusion criteria includes: surgical incision that can be completely 
covered by the PICO NPWT system, BMI ≥ 35 kg/m2 in the 42 days prior to 
surgery, is preoperatively assessed to undergo a procedure with a CDC 
Wound Classification of I (clean) or II (clean contaminated), and is willing 
and able to return for all scheduled and required study visits. Patients 
must have had surgical skin site preparation with chlorhexidine gluconate 
solution (ChloraPrep©), received preoperative surgical prophylaxis 
antibiotics as per protocol, and skin must be closed in a subcuticular 
fashion. Exclusion criteria include delivery for suspected intrauterine 
infection (defined as maternal fever plus one clinical criteria), diagnosis of 
systemic or skin infections at time of delivery, critical illness, or high-risk 
for anesthesia (American Society of Anesthesiologists [ASA] class P4 – P6). 
Sample size is selected to be 200 participants in the PICO group and 200 
participants in a control group that utilizes standard wound dressing 
technique.  
 
Phase: 
3  
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
3 
Description of 
Sites/Facilities Enrolling 
Participants: 
This study will be performed at a single institution, the Long Island Jewish 
Medical Center, an 827-bed voluntary, non-profit tertiary care teaching 
hospital in New Hyde Park, Queens, New York. Patients who present for 
elective or repeat cesarean delivery who meet eligibility criteria at this 
institution only will be recruited for participation in the study. The study 
will not include sites outside of the United States.   
 
 
Description of Study 
Intervention: 
The PICO Single Use Negative Pressure Wound Therapy Device (Smith and 
Nephew Healthcare, Hull, United Kingdom) is a non-significant-risk, FDA 
Class II, medical device commercially available in the USA. The protocol 
will assess the effectiveness and functional performance of the NPWT 
system. The PICO unit is a single patient use, battery-powered, disposable 
unit that can provide continuous 80 - 125 mmHg negative pressure over a 
total of a 7-day therapy period. It is an easy to use device that also 
provides audible and visual alerts for low battery, maximum canister 
volume, and leak conditions. Additional alerts include system error and 
device life-cycle expiration (8 days). It is contained in a water-resistant 
housing, which allows the subject to lightly shower with the device. 
Wound fluids are contained within the 45 mL canister. 
 
The dressing is applied to the wound and extra strips are placed over the 
outside edge to help hold the dressing in place. When the pump is turned 
on, air is pulled out of the dressing and excess fluid from the wound will 
start to enter the dressing. The dressing helps to prevent bacteria from 
entering the wound. It may also improve blood flow to the wound which 
assists healing.  
 
Active Comparator: Standard Dressing 
Standard-of-care includes coverage of the sutured incision with sterile 
gauze and non-penetrable barrier (e.g., surgical tape or Tegaderm™) 
consistent with the national standard for dressing Cesarean delivery 
incisions. These dressings are removed on postoperative day #1 as per 
standard protocol. 
 
  
Study Duration: 
We estimate that 8 months will be required to complete the study from 
when the study opens to enrollment until the completion of data analyses.  
 
Participant Duration: 
It will take 42 +/- 10 days for each individual participant to complete all 
participant visits. 
 
 
 
 
 
 
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
4 
 
1.2 
SCHEMA 
 
Prior to  
Enrollment 
 
 
 
 
 
 
 
 
 
 
Visit 1 
Day 1 
(In hospital) 
Cesarean  
 
 
 
Visit 2 
(In hospital) 
POD#1 
 
 
 
Visit 4 
(Routine  
Postoperative 
office visit) 
POD#7 - 14 
 
 
 
 
Visit 5 
(Routine  
Postoperative 
office visit) 
POD#42 +/- 10 
 
Total N = 396:  Obtain informed consent. Screen potential participants by inclusion and 
exclusion criteria; obtain history, document. 
Perform baseline assessments. 
Record subject demographics and BMI 
Administer initial study intervention: subjects will be randomized to either the current 
standard-of-care dressing applied to the surgical skin site OR the PICO NPWT system to 
the surgical skin site. Subjects must have surgical skin preparation with Chloraprep© 
(chlorhexidine gluconate) solution and have received preoperative antibiotics for surgical 
prophylaxis as per protocol.  
Follow-up assessments of study endpoints and safety 
 
Assessment of surgical site 
Removal of standard-of-care dressing in patients randomized to this group.  
Final Assessment 
Assessment of surgical site 
Arm 2 
N = 198 
Arm 1 
N = 198 
Randomize 
Follow-up assessments of study endpoints and safety 
 
Assessment of surgical site 
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
5 
1.3 
SCHEDULE OF ACTIVITIES (SOA) 
 
 
Procedures 
Screening/Enrollment/
Baseline 
Visit 1, Day 1: Cesarean 
Study Visit 2  
Day 2: Post-Op Day #1 
Study Phone Call    
Post-Op Day 5 – 6 to 
PICO NPWT Subjects 
Study Visit 3 
Post-Op Day 7 - 14 
Final Study Visit 4 
Day 42 +/-10 days  
Informed consent 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
Medical history 
X 
 
 
 
 
Randomization 
X 
 
 
 
 
Administer study 
intervention 
X 
 
 
 
 
Concomitant medication 
review 
X 
X 
 
X 
X 
Physical exam  
 
 
 
 
X 
Vital signs 
X 
X 
 
X 
X 
Height 
 
 
 
 
 
Weight 
X 
 
 
X 
X 
Incision assessment 
 
X 
 
X 
X 
Adverse event review and 
evaluation 
X 
X 
 
X 
X 
Assessment of protocol 
compliance  
 
X 
X 
 
 
Complete Case Report Forms 
(CRFs) 
X 
 
 
 
X 
 
 
2 
 
INTRODUCTION 
 
2.1 
STUDY RATIONALE  
 
Cesarean delivery is the most commonly performed surgical procedure in the United States. 
Approximately 32% of neonates are born via cesarean delivery. Between 1999 and 2010, the incidence 
of obesity in the United States increased from 28.4 – 34.0% in women of childbearing age. Obesity 
contributes significantly to post-surgical complications and any prophylactic measures that can help 
reduce the incidence of these complications will benefit patient care and outcomes. 
 
This will be a randomized, open-label, single-institution, Phase III, comparative interventional study that 
aims to determine if the PICO Single Use Negative Pressure Wound Therapy (NPWT) has an effect on 
incidence of postoperative surgical site complications in patients undergoing cesarean delivery. Subjects 
will be compared to a control arm treated with a standard-of-care surgical incision pressure dressing. 
This prospective clinical study will assess the effectiveness and functional performance of NPWT on 
closed incisions. Clinical outcomes for this study are defined as Surgical Site Occurrences (SSOs) that 
include unanticipated local inflammatory response, prolonged drainage, fluid collection, dehiscence, and 
surgical site infection (SSI) as well as Surgical Incision Interventions (SII). This study will compare these 
outcomes to a control group consisting of Subjects screened for the same inclusion and exclusion 
criteria but treated with a standard-of-care surgical incision dressing. The NPWT is known to reduce 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
6 
surgical site infection rates in the general and trauma surgery literature; however, it has not been 
studied in a large randomized controlled trial in patients undergoing cesarean delivery. A decrease in the 
incidence of surgical site infections and occurrences in this population could potentially have a major 
impact in the care of pregnant obese patients undergoing cesarean delivery.  
 
An RCT to evaluate the clinical effect of NPWT in obese women undergoing cesarean delivery is 
important to provide much-needed evidence in a costly area of healthcare. 
 
 
2.2 
BACKGROUND  
 
Cesarean delivery is the most common surgical procedure performed in the United States. In 2015, the 
Center for Disease Control (CDC) reported 1,272,503 cesarean births in 2015, resulting in an overall 
32.0% cesarean delivery rate. Postpartum surgical site infection (SSI) and wound infections major causes 
of prolonged hospital stay and causes increased costs to the health care system. SSIs complicate a 
significant number of patients who undergo cesarean delivery; approximately 18.4% will experience 
wound infections. 
 
Between 1999 and 2010, the incidence of obesity in the United States increased from 28.4 – 34.0% in 
women of childbearing age. Obese women have the highest risk of surgical site infection after cesarean 
delivery even after adjustment for comorbidities including diabetes mellitus. Management of surgical 
site infection after cesarean delivery can include antibiotics, wound exploration, or surgical 
debridement. Open surgical wounds may be managed using closure by secondary intention or negative 
pressure wound therapy. Non-pregnant patients with surgical site infection after laparotomy are 
managed with closure by secondary intention or the addition of negative pressure wound therapy to the 
wound; this has been associated with improved healing times compared with allowing closure by 
secondary intention alone. 
 
There are currently two published trials evaluating post-cesarean surgical site complications in patients 
who had a cesarean delivery and received either a NPWT dressing versus a standard-of-care pressure 
dressing. There are several trials that evaluate post-surgical complications in the Trauma, General, and 
Orthopedic surgery literature.  
 
A randomized controlled trial by Gunatilake RP et al published in April 2017 compared 46 obese patients 
who were randomized to a NPWT system (the PREVENA Incision Management System manufactured by 
KCI) to 46 obese patients who were randomized to standard-of-care dressings. The primary endpoints in 
this study were: unanticipated local inflammatory response, prolonged drainage, fluid collection, 
dehiscence, and surgical site infection. The secondary endpoints were: incidence of subjects with 
surgical interventions (antimicrobials, surgical drainage of incision, adjunctive negative pressure 
evaluation, debridement, or reoperation).  Surgical site assessments also included supplementary 
outcomes of incisional pain scored. This study did not show statistically significant differences between 
postoperative outcomes in patients who were randomized to the NPWT system versus the standard of 
care dressing; however, they found a trend towards reduction in incisional wound complications and a 
statistically significant reduction in postoperative pain scales.  
 
A survey by Searle RJ et al published in August 2017 reported audit data from 399 patients with a BMI ≥ 
35 kg/m2 who used PICO dressings on closed cesarean surgical incisions in Ireland and found that 9% of 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
7 
these patients developed an SSI, which is less than the previously reported 19.3% in a similar 
population. In addition, these patients had a much lower readmission rate due to SSI (0.8% versus 
previously reported 4.3%).  
 
This trial is clinically relevant to address potential prophylactic methods to prevent SSI and SSO in the 
obese pregnant population. If PICO NPWT contributes to the reduction of SSI and SSO, its use will have a 
large impact on patient care and a huge cost savings for the health system.  
 
2.3 
RISK/BENEFIT ASSESSMENT   
 
2.3.1 KNOWN POTENTIAL RISKS  
 
Immediate risks: 
 
The PICO pumps contain a MAGNET. Keep the PICO pumps at least 4 inches (10 cm) away from other 
medical devices at all times. As with all electrical medical equipment, failure to maintain appropriate 
distance may disrupt the operation of nearby medical devices. 
 
The first time the PICO pump is turned on, subjects may feel a slight pulling or drawing sensation. In 
addition, some patients feel discomfort when dressings are changed or removed; however, this 
discomfort is not expected to be more than the discomfort associated with removal of standard of care 
dressings.  
 
There is a small risk of skin reddening or sensitization; however, this reaction is not expected to be more 
frequent than that associated with standard dressings.  
 
Patients may feel embarrassed from being part of a study that is investigating an obese patient 
population.  
Long-term Risks: 
There are no known long-term risks associated with the use of PICO dressing.  
 
2.3.2 KNOWN POTENTIAL BENEFITS  
 
NPWT is a non-significant-risk, FDA Class II, medical device commercially available in the USA.  
 
Immediate potential benefits: 
 
An immediate potential benefit of NPWTs is the ease in its application. It provides audible and visual 
alerts for low battery, maximum canister volume, and leak conditions. There may be a decreased risk of 
surgical site occurrences, infections, and readmission and reduction in postoperative pain with PICO 
dressing use.  
 
Long-term potential benefits: 
 
Decreased incidence of surgical site infections and occurrences can benefit patients by reducing long-
term wound infections such as delayed closure or healing, need for reoperation for wound closure, pain 
syndromes, or decreased tensile strength of wounds.  

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
8 
 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
 
The only potential risk is embarrassment from being in a study that is investigating a potential 
prophylactic dressing in an obese population. Consent will be obtained discreetly to minimize this risk.  
 
There are minimal risks of participation in this study that far outweigh the value that information 
regarding a prophylactic dressing could decrease risk of surgical site infection in obese postpartum 
patients would gain from this study. The PICO dressing is already used by some providers after cesarean 
delivery and so is considered an option for postoperative care of these patients.  
 
3 
OBJECTIVES AND ENDPOINTS 
 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
 
 
The incidence of postoperative 
Surgical Site Occurrences (SSOs) 
up to Day 42 (+/- 10 Days) post 
Cesarean Section.  
 
 
The incidence of postoperative 
surgical site occurrences (SSOs) post 
Cesarean delivery. SSOs include: 
- Unanticipated local inflammatory 
response 
- Prolonged drainage 
- Fluid collection-  
Dehiscence 
- Surgical site infection (SSI) 
 
 
A percentage of 
cesarean deliveries 
result in SSO leading to 
prolonged wound 
healing and 
postoperative pain, 
increased rates of 
secondary infection 
and re-hospitalization, 
decreased patient 
satisfaction, and 
increased costs of 
medical care. 
 
NPWT has been shown 
to decrease rates of 
postoperative infection 
and wound dehiscence 
in a non-obstetrical 
population.  
Secondary 
 
 
Incidence Rate of Surgical Incision 
Intervention (SII) up to Day 42 (+/- 
10 Days) Post Cesarean delivery.  
Incidence rate of surgical incision 
intervention (SII) post Cesarean 
delivery. 
Interventions include: 
These interventions 
are costly to the 
healthcare system and 
reduce quality of care 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
9 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
 
- Antimicrobials for surgical site 
infection 
- Surgical drainage of the incision 
- Surgical incision packing 
- Adjunctive negative pressure 
therapy 
- Debridement 
- Re-operation 
 
and decrease patient 
satisfaction. 
Interventions that can 
prevent these 
necessary procedures 
are important to 
justify.  
 
 
 
 
4 
STUDY DESIGN  
 
4.1 
OVERALL DESIGN 
 
 
Hypothesis: We hypothesize that the PICO NPWT dressing will decrease the incidence of surgical site 
infections and occurrences in patients with a BMI ≥ 35 kg/m2 undergoing cesarean delivery.  
 
Trial phase: 3 
 
Description of trial design: A randomized, controlled, single-institution, interventional clinical trial to 
evaluate clinical outcomes. 
 
Methods used to minimize bias:  
 
Selection bias will be minimized by reducing the exclusion criteria to include all eligible subjects. Also, 
the randomization sequence will be concealed from investigators at the time of obtaining consent from 
the trial participants.  
 
There will be no blinding in the study.  Neither the participants nor the physicians will be blinded to the 
study treatment they are randomized to.  
 
Masking or blinding is not feasible in this study because the size, shape, and components of the PICO 
and standard dressings are different as is the length of time each dressing is worn. However, participant 
ascertainment biased will be minimized because diagnosis of an SSO/SSI and need for SII will be made 
and determined by skilled resident and attending physicians at each of the routine visits, not by patient 
report. Co-intervention bias will be minimized because there will be no changes in routine post-
operative or nursing care instructions between groups.  
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
10 
The statisticians who are responsible for analyzing the results will not be made aware which group 
received the PICO NPWT dressing versus the standard wound dressing.  
 
Recruitment bias will be minimized by ensuring that all participants who meet inclusion and exclusion 
criteria with a planned cesarean delivery during the specified time frame are approached and offered 
participation in the study. Most hospitals utilize standard of care wound dressings similar to the dressing 
described for the standard dressing group in this proposal, which will minimize clinical practice bias.  
 
Number of study groups/arms: There will be two study groups, Group 1 will be randomized to receive 
the standard of care pressure dressing and Group 2 will be randomized to receive the PICO NPWT 
dressing postoperatively.  
 
Study intervention duration: The study period will begin with the day of the scheduled cesarean delivery 
procedure and end 42 +/- 10 days postoperatively.  
 
Name of study intervention: The Smith & Nephew PICO single-use negative pressure wound therapy 
system. 
 
Planned interim analysis: There are no planned formal interim analyses.  
 
Stratification: Subjects will be stratified and sub-analyses performed by BMI: 35 – 39.9 kg/m2, 40 – 44.9 
kg/m2, 45 – 49.9 kg/m2, 50 – 54.9 kg/m2. 
 
 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
 
The control group will be randomized to receive the standard-of-care pressure dressing that includes 
coverage of the sutured incision with sterile gauze and non-penetrable barrier (e.g., Tegaderm™) 
consistent with the national standard for dressing Cesarean section incisions. These dressings are 
removed on postoperative day #1 as per standard protocol.  
 
The control dressing will be the current standard of care pressure dressing that is used on all patients 
undergoing cesarean delivery. There are no known or potential problems associated with the control 
group. All other interventions will be as per current protocol.  
 
The study design is a superiority randomized controlled trial (RCT) because the aim is to show that the 
PICO NPWT is superior to the standard pressure dressing in regards to incidence of SSIs and SSOs.  
 
 
4.3 
JUSTIFICATION FOR DOSE 
 
Not applicable.  
 
4.4 
END OF STUDY DEFINITION 
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
11 
A participant is considered to have completed the study if she has completed all phases of the study 
including the last visit or the last scheduled procedure shown in the Schedule of Activities (SoA), Section 
1.3. 
 
5 
STUDY POPULATION 
We will recruit obese women undergoing elective cesarean section.  Subjects who consent will be 
randomized to use either the PICO NPWT or standard of care dressing. 
 
Females aged ≥ 18 years with BMI ≥ 35 kg/m2 who are able to provide consent and are undergoing a 
planned cesarean delivery using subcuticular skin closure technique at the Long Island Jewish Medical 
Center. 
 
Screening procedures will not be performed under a separate screening consent form. 
 
5.1 
INCLUSION CRITERIA 
 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
 
1. Provision of signed and dated informed consent form 
2. Stated willingness to comply with all study procedures and availability for the duration of the 
study; willing and able to return for all scheduled and required study visits 
3. Female, aged 18 – 55 years 
4. BMI ≥ 35 kg/m2 in the 42 days prior to surgery 
5. In good general health as evidenced by medical history with a 24 – 41 weeks gestational age 
pregnancy scheduled for cesarean delivery for any routine indication (repeat procedure, breech 
presentation, abnormal placentation, uterine anomaly, maternal medical condition, or elective)  
6. Ability to and willingness to adhere to the PICO negative pressure wound therapy regimen 
7. Surgical skin site preparation with chlorhexidine gluconate solution (ChloraPrep©) 
8. Received preoperative surgical prophylaxis antibiotics as per protocol  
9. Surgical incision that can be covered completely by the NPWT skin system 
10. Pre-operatively assessed to undergo a procedure with a CDC Wound Classification of: 
a. Class I (Clean): An uninfected operative wound in which no inflammation is encountered 
and the respiratory, alimentary, genital, or uninfected urinary tract is not entered 
- OR - 
b. Class II (Clean Contaminated): An operative wound in which the respiratory, alimentary, 
genital, or uninfected urinary tract are entered under controlled conditions and without 
unusual contamination 
11. Wound hemostasis has been achieved 
 
5.2 
EXCLUSION CRITERIA 
 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
1. Cesarean delivery before fetal viability (24 0/7 weeks gestational age) 
2. Unplanned Cesarean delivery 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
12 
3. Fetal death 
4. Known allergic reactions to components of the PICO NPWT system 
5. Systemic bacterial or fungal infection at the time of surgery 
6. Diagnosis of systemic or remote-site skin infections at time of delivery 
7. Treatment with another investigational drug or other intervention within 7 days prior to 
cesarean delivery or 42 +/- 10 days after cesarean delivery 
8. Delivery for suspected intrauterine infection (defined as maternal fever plus one clinical criteria) 
9. Critical illness or immune-compromising disease (eg acquired immunodeficiency syndrome) 
10. Chronic steroid use 
11. Pre-operatively assessed to have a CDC Wound Classification of: 
o Class III (Contaminated): Open, fresh, accidental wounds, and/or major breaks in sterile 
technique or gross spillage from the gastrointestinal tract 
- OR - 
o Class IV (Dirty-Infected): Old traumatic wounds with retained devitalized tissue and 
those that involve existing clinical infection or perforated viscera 
12. High-risk for anesthesia (American Society of Anesthesiologists [ASA] class P4 – P6) 
13. Intra-operative hemorrhage requiring blood transfusion, disseminated-intravascular 
coagulopathy (DIC) or any other medical or surgical condition during the Cesarean section 
deemed by the investigator to pose a prohibitively high risk for surgical re-exploration 
14. Life expectancy of < 12 months 
15. Unable to speak or understand English, with no interpreter available 
 
5.3 
LIFESTYLE CONSIDERATIONS 
 
Not applicable.  
 
5.4 
SCREEN FAILURES 
 
Individuals who do not meet the criteria for participation in this trial (screen failure) because of an early 
delivery or delivery at a time other than their scheduled delivery time may be rescreened but cannot 
participate in the study. Rescreened participants should be assigned the same participant number as for 
the initial screening. 
 
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
 
Potential study participants will be approached by study personnel at time of presentation for her 
scheduled cesarean delivery at Labor and Delivery at the Long Island Jewish Medical Center.  
 
There are approximately 1 – 2 scheduled cesarean deliveries per day between the Ambulatory Care 
Clinic, Garden City OBGYN (Long Island Jewish Medical Center/Northwell Health OB/GYN practice) and 
the Women’s Comprehensive Care Center (Long Island Jewish Medical Center Faculty practice). 
Approximately 34% of these patients are obese. We anticipate a 75% accrual rate.  
 
Patients will be identified and approached while they are waiting for cesarean delivery surgery time by 
study personnel. Study personnel will show the patients an example of a PICO dressing and a standard 
of care dressing and explain study protocol and procedures.  

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
13 
 
A pregnant participant population must be used as subjects in this study because the primary endpoint 
is SSO and SSI incidence in patients who are undergoing cesarean delivery.  
 
Participants will not be compensated for participation in the study.  
 
6 
STUDY INTERVENTION 
 
6.1 
STUDY INTERVENTION(S) ADMINISTRATION 
 
6.1.1 STUDY INTERVENTION DESCRIPTION 
 
The PICO Single Use Negative Pressure Wound Therapy Device (Smith and Nephew Healthcare, Hull, 
United Kingdom) is a non-significant-risk, FDA Class II, medical device commercially available in the USA. 
The PICO unit is a single patient use, battery-powered, disposable unit that can provide continuous 80 - 
125 mmHg negative pressure over a 5 to 7-day therapy period. It is an easy to use device that also 
provides audible and visual alerts for low battery, maximum canister volume, and leak conditions. 
Additional alerts include system error and device life-cycle expiration (7 days). It is contained in a water-
resistant housing, which allows the subject to lightly shower with the device. Wound fluids are 
contained within the 45 mL canister. 
The dressing is applied to the wound and extra strips are placed over the outside edge to help hold the 
dressing in place. When the pump is turned on, air is pulled out of the dressing and excess fluid from the 
wound will start to enter the dressing. The dressing helps to prevent bacteria from entering the wound. 
It may also improve blood flow to the wound which will help it to heal. 
 
The standard-of-care is consistent with the national standard for dressing Cesarean section incisions and 
includes, but not limited to, coverage of the sutured incision with sterile gauze and non-penetrable 
barrier (e.g., Tegaderm™). The non-penetrable barrier may be left in place for a minimum of 1 day and 
no longer than 2 days (± 4 hours) to promote epithelialization of the surgical incision edges. After the 
dressing is removed, the surgical site is left exposed to air to promote further healing. Other therapies 
include traditional gauze dressings with or without advanced therapies such as hydrocolloids, growth 
factors, and Negative Pressure Wound Therapies. 
 
6.1.2 DOSING AND ADMINISTRATION 
 
The PICO dressing provides 80 - 125 mmHg negative pressure over a 5 day therapy period as a standard 
setting and this will be used in all patients.  
 
Patients will be taught how to remove the dressing at home after the total 5-day period. Dressing 
removal is not difficult and should not cause excess pain or discomfort. In order to remove the dressing, 
the pump is disconnected and the dressing is removed by gently pulling the adhesive edges. The entire 
dressing and pump can be disposed of in the garbage.  
 
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
14 
 
6.2.1 ACQUISITION AND ACCOUNTABILITY 
 
The PICO dressing and supplies for the pressure dressing are available on the Long Island Jewish Medical 
Center Labor and Delivery Unit. Study personnel will obtain dressing and apply dressing.  
 
6.2.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
 
The Smith and Nephew PICO device (Figure 1) is packaged for single use and does not need returning or 
sterilization. The battery pack retains its charge for 7 days delivering a continuous negative pressure. 
The dressing is designed in 4 layers: top film layer with a high moisture vapor transmission rate (MVTR) 
allows one-way transpiration of exudate vapor, proprietary absorbent layer moves exudate away from 
the wound and initiates evaporation, airlock layer maintains open airflow and allows even distribution of 
negative pressure across the dressing, and the wound contact layer is composed of silicon and does not 
lead to in-growth of granulation tissue into the dressing material to decrease pain with removal. The 
pump is a water-resistant, quiet, pocket-sized, canister-free system that uses two AA lithium batteries 
that last for the 5 – 7 day therapy. The device is packaged in a disposable cardboard box (Figure 2) and 
can be kept at room temperature. PICO™ is supplied in a pack that can be taken off the shelf when 
required. It contains a single use pump, which lasts for 7 days and two individually packed dressings and 
fixation strips (allowing for the wound to be inspected during those 7 days). 
 
PICO specifics from manufacturer product safety data sheet: 
Dressing: Laminate of silicone/acrylic adhesive coated polyurethane films to polyethylene layer and 
polyacrylate/cellulose airlaid layer. A polyurethane port and an acrylic copolymer/nylon filter membrane 
are bonded to the laminate using acrylic adhesive. PVC tubing is also bonded to the polyurethane port 
using an acrylic adhesive. Laminate is placed on HDPE handles.  
Secondary fixation strips: Laminate of acrylic adhesive coated on polyurethane film placed between 
polyethylene, polypropylene and paper carriers.  
Pump: Internal components consist of PCBA (Printed Circuit Board Assembly consisting of multiple 
electronic components, PCB and soldered joints), electric motor driven diaphragm pump, air manifold 
(thermoplastic elastomer), wiring, connections and steel battery contacts. External components consist 
of 2 case halves (ABS thermoplastic), air inlet connection (ABS thermoplastic), button (thermoplastic 
elastomer), lenses (polystyrene) and battery cover (ABS thermoplastic).  
 
 
A 10 x 30cm PICO dressing size fits most cesarean section incisions, and larger and smaller sized 
dressings are available.  
 
The standard pressure dressing is composed of Telfa®, a non-adherent wound dressing which consists of 
absorbent cotton fibers impregnated with polyhexamethylene biguanide enclosed in a sleeve of 
thermoplastic polymers, cotton 4” x 4” sterile mesh gauze manufactured by Medronic (Minneapolis, 
MN, USA) and a non-penetrable barrier (e.g., tape or Tegaderm™ adhesive film (3M, USA). 
 
 
Figure 1: 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
15 
 
 
 
 
 
Figure 2: 
   
 
6.2.3 PRODUCT STORAGE AND STABILITY 
Both the standard dressing supplies and the PICO dressing can be stored in the operating room storage 
units. Both must be stored in a cool, dry place <25°C and kept away from sources of ignition and strong 
light sources.  
 
 
6.2.4 PREPARATION 
 
Both dressing are easily applied in a few minutes. There is no required thawing, diluting, mixing, 
reconstitution/preparation, or difficult assembly. 
 
How to apply instructions from PICO package insert: 
 
Application 
1. Remove any excess hair to ensure close approximation of the dressing to the wound. If 
necessary, irrigate the wound with sterile saline and pat the wound dry. 
 
2. Using a clean technique, peel off the central release handle and place the dressing 
centrally over the wound to reduce the chance of wound fluid coming into contact with 
the port. The port should be uppermost from the wound (depending on the patient’s 
primary position), placed on intact skin and not extend over the wound to prevent fluid 
pooling around the port and blocking the negative pressure. Remove the other two 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
16 
handles and smooth the dressing around the wound to prevent creasing. Reposition if 
required to ensure border is not creased. 
 
3. Once the dressing is in place, remove the pump and the batteries from the tray. Insert 
the batteries. Replace the cover. Following this all three lights should flash once. 
 
4. Join the pump to the dressing by twisting together the tubing connectors. Press the 
orange button to start the application of negative pressure. The green light will start to 
flash indicating the system is working properly. 
Depending on the size of the wound, the pump should take up to 30 seconds to establish 
negative pressure wound therapy. 
 
5. If using SKIN-PREP™ prior to application of the fixation strips (see Precautions), wipe the 
area surrounding the dressing and allow skin to dry. 
 
6. Apply the fixation strips to each of the four sides of the dressing. Remove top carrier on 
the strip after each one has been applied. These strips maintain the seal over the wear 
time of the dressing. In awkward areas, it may be useful to apply the strips to help achieve 
a seal prior to switching on the pump. Place each strip so that it overlaps the dressing 
border by approximately 1cm (2/5in.). Ensure tubing is not twisted or trapped between 
clothing. 
Please note that if at any time the fixation strips are removed, the dressing should also 
be replaced. 
 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
 
This trial tests a clinical intervention that is not amenable to protection against performance bias 
through the blinding of participants, clinical staff or data collectors. There will be no blinding in the 
study.  Neither the participants nor the physicians will be blinded to the study treatment they are 
randomized to. 
The Biostatistics Unit at the Feinstein Institute for Medical Research [BU-FIMR] will develop a 
randomization plan for the study using the Biostatistics Randomization Management System [BRMS].  
BRMS is a secure, HIPAA-compliant, web-based application that allows investigators to randomize 
subjects into randomized clinical trials (RCTs) using a personal computer with internet access. The BRMS 
allows for multi-center, stratified, and single/double blinded RCTs.  Randomization notifications are 
automatically sent to the PI and other authorized personnel. BRMS maintains compliance in RCTs. 
A randomization schema will be generated by the BU-FIMR using the method of permuted blocks.  
Subjects will be randomly assigned in a 1:1 ratio to either ‘PICO’ or ‘STANDARD DRESSING’.  Details of 
the randomization procedure, including required record keeping will be further developed upon 
approval of the protocol.   
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
17 
The RA will randomize participants in the operating room at the start of their cesarean procedure and 
advise the operating obstetrician and nursing staff of the allocated treatment as close to the end of the 
procedure as possible in order to minimize performance bias. 
 
To minimize the potential for outcome detection bias, an expert statistician, blinded to group allocation, 
will assess the data to determine the primary outcome. 
 
Subjective outcomes (SSI/SSOs) are reported by patients or observed by study personnel, who cannot be 
blinded because they need to check the dressings. 
 
Outcome assessors will be masked to allocation. 
 
 
6.4 
STUDY INTERVENTION COMPLIANCE 
 
In order to complete the study intervention, the participant must have worn the PICO NPWT dressing for 
a minimum of 5 days after surgery. On the fifth postoperative day, the participant may remove the 
dressing at home. A phone call to each participant randomized to the PICO NPWT dressing will be made 
on the 5th or 6th postoperative day (after discharge to the hospital) to verify compliance with the use of 
the device. No documents are mandatory for the participants to complete and adherence to the 
protocol will be verified by patient report only.  
 
6.5 
CONCOMITANT THERAPY 
 
Not applicable. 
 
6.5.1 RESCUE MEDICINE 
   
Not applicable. 
 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
 
Discontinuation from PICO dressing compliance before a minimum of 5 days does not mean 
discontinuation from the study, and remaining study procedures should be completed as indicated by 
the study protocol.  If a clinically significant finding is identified (including, but not limited to changes 
from baseline) after enrollment, the investigator or qualified designee will determine if any change in 
participant management is needed. Any new clinically relevant finding will be reported as an adverse 
event (AE). 
 
The data to be collected at the time of study intervention discontinuation will include the following: 
• 
Reason the PICO dressing was discontinued: 
o Patient discomfort, 
o Misunderstanding of use, 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
18 
o Loss of supplies,  
o etc. 
• 
Incision assessment 
• 
SSI or SSO  
 
 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue or withdraw a participant from the study for the following reasons: 
 
• 
Significant study intervention non-compliance  
• 
If any clinical adverse event (AE), or other medical condition or situation occurs such that 
continued participation in the study would not be in the best interest of the participant 
• 
Disease progression which requires discontinuation of the study intervention 
• 
If the participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
• 
The PICO device is not compatible with MRI and cannot be taken in to an MRI suite. If the 
patient requires MRI, the PICO dressing will need to be discontinued 
The reason for participant discontinuation or withdrawal from the study will be recorded. Subjects who 
sign the informed consent form and are randomized but do not receive the study intervention may be 
replaced.  Subjects who sign the informed consent form, and are randomized and receive the study 
intervention, and subsequently withdraw, or are withdrawn or discontinued from the study, will be 
replaced. 
7.3 
LOST TO FOLLOW-UP 
 
A participant will be considered lost to follow-up if he or she fails to return for 2 scheduled visits and is 
unable to be contacted by the study site staff.  
 
The following actions must be taken if a participant fails to return to the clinic for a required study visit: 
• 
The site will attempt to contact the participant and reschedule the missed visit within 10 days 
and counsel the participant on the importance of maintaining the assigned visit schedule and 
ascertain if the participant wishes to and/or should continue in the study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee will make every 
effort to regain contact with the participant (where possible, 3 telephone calls and, if necessary, 
a certified letter to the participant’s last known mailing address or local equivalent methods). 
These contact attempts should be documented in the participant’s medical record or study file.  
• 
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
 
 
8 
STUDY ASSESSMENTS AND PROCEDURES 
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
19 
8.1 
EFFICACY ASSESSMENTS  
 
Screening procedures and evaluations may be performed on the day of enrollment but no more than 10 
days prior to the day of enrollment. The screening process will be a discussion with the patient and 
review of medical history and height and weight to determine eligibility, and explanation of the study 
rational and study protocol, and demonstration of the two dressing options. Informed consent will then 
be obtained and patients will have the opportunity to ask questions.  
 
The study intervention will be administered at the end of the scheduled cesarean delivery procedure. 
Standard dressings will be removed on postoperative day 1 as per current protocol and PICO NPWT 
dressings will be changed if necessary in the hospital and removed on postoperative day 5 by the patient 
at home.  
 
Procedures that will be completed during the study as part of regular standard of clinical care: the 
post-operative visits on day 7 – 14 and 42 +/- 10 days are part of regular standard of clinical care and the 
outcomes and incision assessments after the participating patients leave the hospital will be performed 
by skilled residents and attending physicians at these visits. Charts will be reviewed to ascertain if 
SSO/SSIs were diagnosed or SIIs were necessary.  
 
During these regularly scheduled visits, a physical examination and incision assessment will be 
performed including weight, abdominal exam, incision exam, and all regular postoperative visit exams 
including breast and pelvic (at the 42 +/- 10 day visit only) as part of the routine standard of care.  
 
If follow-up visits or unscheduled visits are required for treatment of SSO/SSIs or SIIs, information 
regarding the type of SSO or SII required will be obtained from review of the medical chart.  
 
Surgical Site Occurences include: unanticipated local inflammatory response, prolonged drainage, fluid 
collection, dehiscence, surgical site infection (SSI). SSI is diagnosed using the following criteria: warmth 
to touch, pain with palpation, skin redness, irritation, or induration, large amount of drainage or 
purulent drainage, fluctuance suspicious for wound abscess, fever, and/or wound odor.  
 
Surgical Site Interventions include: Antimicrobials for surgical site infection, surgical drainage of the 
incision, surgical incision packing, adjunctive negative pressure therapy, debridement, or re-operation. 
 
Information that will be obtained through review of existing data: 
• 
Age 
• 
BMI (kg/m2) 
• 
Medical comorbidities 
• 
Pregnancy history (term, preterm, abortions, and living history) 
• 
Mode of prior deliveries, if applicable 
• 
Indication for cesarean delivery  
• 
Incision assessment information from residents and attendings at follow-up visits.  
 
 
8.2 
SAFETY AND OTHER ASSESSMENTS 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
20 
 
Sequence of events that will occur during screening process: 
1. Review of scheduled cesarean delivery schedule for the day. 
a. Screening procedures must be performed within 10 days of study enrollment.  
2. Review of medical charts to assess for eligibility (see below). 
3. Approach patient and explain trial and interventions.  
4. No dietary or activity considerations are required for participation in the trial; however, 
patients will be counseled that the PICO dressing protocol requires the dressing to be in 
place for a minimum of 5 days.  
5. Assessment of ability to comply with study intervention.  
6. Obtain consent. 
7. The patient will not be randomized until presentation to labor and delivery and 
randomization group will not be exposed to healthcare team until as close as possible to the 
end of the surgical procedure.  
 
Information that will be obtained through review of existing data (i.e. patient’s medical chart): 
• 
Age 
• 
BMI (kg/m2) 
• 
Medical comorbidities 
• 
Pregnancy history (term, preterm, abortions, and living history) 
• 
Mode of prior deliveries, if applicable 
• 
Indication for cesarean delivery  
• 
Incision assessment information from residents and attendings at follow-up visits 
 
No study specific procedures will be performed and so no results will be provided to patients.  
 
List and description of the following procedures/evaluations, as applicable: 
• 
Physical examination: height and weight, fundal height, fetal heart rate measurement (initial 
study day prior to administration of intervention, and incision assessment). 
• 
Vital signs: temperature, pulse, and blood pressure.  
• 
Assessment of adverse events. Adverse events will be followed by attending physicians and 
research PI Anar Yukhayev, MD. There are minimal expected adverse events that are not beyond 
the potential adverse events that could occur from the regular standard dressing (i.e. dressing 
tape site reaction or allergy to tape) 
 
   
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
 
8.3.1 DEFINITION OF ADVERSE EVENTS (AE) 
 
Adverse event means any untoward medical occurrence associated with the use of an intervention in 
humans, whether or not considered intervention-related (21 CFR 312.32 (a)). 
 
 
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE)  
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
21 
An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of either the 
investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse 
event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant 
incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital 
anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or 
require hospitalization may be considered serious when, based upon appropriate medical judgment, 
they may jeopardize the participant and may require medical or surgical intervention to prevent one of 
the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do 
not result in inpatient hospitalization, or the development of drug dependency or drug abuse. 
 
8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.3.3.1 
SEVERITY OF EVENT 
 
For adverse events (AEs) not included in the protocol defined grading system, the following guidelines 
will be used to describe severity: 
 
• 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities.  
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating.  Of note, the term “severe” does not necessarily equate to “serious”. 
 
 
8.3.3.2 RELATIONSHIP TO STUDY INTERVENTION 
All adverse events (AEs) must have their relationship to study intervention assessed by the clinician who 
examines and evaluates the participant based on temporal relationship and his/her clinical judgment. 
The degree of certainty about causality will be graded using the categories below. In a clinical trial, the 
study product must always be suspect.  
 
• 
Related – The AE is known to occur with the study intervention, there is a reasonable possibility 
that the study intervention caused the AE, or there is a temporal relationship between the study 
intervention and event. Reasonable possibility means that there is evidence to suggest a causal 
relationship between the study intervention and the AE. 
• 
Not Related – There is not a reasonable possibility that the administration of the study 
intervention caused the event, there is no temporal relationship between the study intervention 
and event onset, or an alternate etiology has been established. 
 
OR 
 
• 
Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test 
result, occurs in a plausible time relationship to study intervention administration and cannot be 
explained by concurrent disease or other drugs or chemicals. The response to withdrawal of the 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
22 
study intervention (dechallenge) should be clinically plausible. The event must be 
pharmacologically or phenomenologically definitive, with use of a satisfactory rechallenge 
procedure if necessary. 
• 
Probably Related – There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test result, occurs within 
a reasonable time after administration of the study intervention, is unlikely to be attributed to 
concurrent disease or other drugs or chemicals, and follows a clinically reasonable response on 
withdrawal (dechallenge). Rechallenge information is not required to fulfill this definition. 
• 
Potentially Related – There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of the trial medication). However, other 
factors may have contributed to the event (e.g., the participant’s clinical condition, other 
concomitant events). Although an AE may rate only as “possibly related” soon after discovery, it 
can be flagged as requiring more information and later be upgraded to “probably related” or 
“definitely related”, as appropriate. 
• 
Unlikely to be related – A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to study intervention administration makes a causal relationship 
improbable (e.g., the event did not occur within a reasonable time after administration of the 
study intervention) and in which other drugs or chemicals or underlying disease provides 
plausible explanations (e.g., the participant’s clinical condition, other concomitant treatments). 
• 
Not Related – The AE is completely independent of study intervention administration, and/or 
evidence exists that the event is definitely related to another etiology. There must be an 
alternative, definitive etiology documented by the clinician. 
 
8.3.3.3 EXPECTEDNESS  
 
Anar Yukhayev, MD will be responsible for determining whether an adverse event (AE) is expected or 
unexpected.  An AE will be considered unexpected if the nature, severity, or frequency of the event is 
not consistent with the risk information previously described for the study intervention. 
 
8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the attention of 
study personnel during study visits and interviews of a study participant presenting for medical care, or 
upon review by a study monitor. 
 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured on the 
appropriate case report form (CRF). Information to be collected includes event description, time of 
onset, clinician’s assessment of severity, relationship to study product (assessed only by those with the 
training and authority to make a diagnosis), and time of resolution/stabilization of the event. All AEs 
occurring while on study must be documented appropriately regardless of relationship. All AEs will be 
followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at any 
time during the study, it will be recorded as an AE.  
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
23 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. AEs characterized as intermittent require documentation of 
onset and duration of each episode. 
 
Anar Yukhayev, MD will record all reportable events with start dates occurring any time after informed 
consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study 
participation.  At each study visit, the investigator will inquire about the occurrence of AE/SAEs since the 
last visit.  Events will be followed for outcome information until resolution or stabilization. 
 
8.3.5 ADVERSE EVENT REPORTING  
 
Anar Yukhayev, MD will record all reportable events with start dates occurring any time after informed 
consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study 
participation.   
 
8.3.6 SERIOUS ADVERSE EVENT REPORTING  
 
The study investigator shall complete an Unanticipated Adverse Device Effect Form and submit to the 
study sponsor and to the reviewing Institutional Review Board (IRB) as soon as possible, but in no event 
later than 10 working days after the investigator first learns of the effect.  The study sponsor is 
responsible for conducting an evaluation of an unanticipated adverse device effect and shall report the 
results of such evaluation to the Food and Drug Administration (FDA) and to all reviewing IRBs and 
participating investigators within 10 working days after the sponsor first receives notice of the effect. 
Thereafter, the sponsor shall submit such additional reports concerning the effect as FDA requests. 
 
 
8.3.7 REPORTING EVENTS TO PARTICIPANTS  
 
Not applicable.  
 
8.3.8 EVENTS OF SPECIAL INTEREST  
 
Not applicable. 
 
8.3.9 REPORTING OF PREGNANCY  
 
Not applicable.  
 
 
8.4 
UNANTICIPATED PROBLEMS 
 
8.4.1 DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
 
The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks to 
participants or others to include, in general, any incident, experience, or outcome that meets all of the 
following criteria: 
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
24 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the Institutional Review Board (IRB)-
approved research protocol and informed consent document; and (b) the characteristics of the 
participant population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized. 
 
 
This definition could include an unanticipated adverse device effect, any serious adverse effect on 
health or safety or any life-threatening problem or death caused by, or associated with, a device, if that 
effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan or application), or any other 
unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of 
subjects (21 CFR 812.3(s)). 
 
8.4.2  UNANTICIPATED PROBLEM REPORTING  
 
The investigator will report unanticipated problems (UPs) to the reviewing Institutional Review Board 
(IRB) and to the Data Coordinating Center (DCC)/lead principal investigator (PI). The UP report will 
include the following information: 
 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project 
number; 
• 
A detailed description of the event, incident, experience, or outcome;  
• 
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP;  
• 
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP. 
 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline:   
 
• 
UPs that are serious adverse events (SAEs) will be reported to the IRB and to the DCC/study 
sponsor within 30 days of the investigator becoming aware of the event.  
• 
Any other UP will be reported to the IRB and to the DCC/study sponsor within 30 days of of the 
investigator becoming aware of the problem.  
• 
All UPs should be reported to appropriate institutional officials (as required by an institution’s 
written reporting procedures), the supporting agency head (or designee), and the Office for 
Human Research Protections (OHRP) within 30 days of the IRB’s receipt of the report of the 
problem from the investigator. 
 
 
An investigator shall submit to the sponsor and to the reviewing Institutional Review Board (IRB) a 
report of any unanticipated adverse device effect occurring during an investigation as soon as possible, 
but in no event later than 10 working days after the investigator first learns of the effect (21 CFR 
812.150(a)(1)), A sponsor who conducts an evaluation of an unanticipated adverse device effect under 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
25 
812.46(b) shall report the results of such evaluation to the Food and Drug Administration (FDA) and to 
all reviewing IRB's and participating investigators within 10 working days after the sponsor first receives 
notice of the effect. Thereafter the sponsor shall submit such additional reports concerning the effect as 
FDA requests (21 CFR 812.150(b)(1)).    
 
 
8.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
 
Not applicable.  
 
9 
STATISTICAL CONSIDERATIONS  
 
9.1 
STATISTICAL HYPOTHESES 
 
• 
Primary Efficacy Endpoint(s):  
 
The Smith and Nephew PICO NPWT dressing is superior to the standard cesarean incision dressing in 
preventing surgical site occurrences.  
 
Null: The Smith and Nephew PICO NPWT dressing is NOT superior to the standard cesarean incision 
dressing in preventing surgical site occurrences.  
 
 
• 
Secondary Efficacy Endpoint(s): 
 
The Smith and Nephew PICO NPWT dressing is superior to the standard cesarean incision dressing in 
preventing surgical site infections.  
 
Null: The Smith and Nephew PICO NPWT dressing is NOT superior to the standard cesarean incision 
dressing in preventing surgical site infections.  
 
9.2 
SAMPLE SIZE DETERMINATION 
 
• 
Outcome measure used for calculations (almost always the primary variable): incidence of 
surgical site occurrences.  
• 
Type I error rate (alpha): 0.05 (5%) 
• 
Power level: 80%  
 
Based on results from several clinical studies and the American Congress of OBGYN Practice Bulletin on 
Obesity in Pregnancy, we estimate the proportion of subjects with surgical site occurrences among 
obese women who undergo elective cesarean surgery to be about 18%. We accept that an absolute 
difference between study groups of 10%, will be a clinically meaningful difference.  Therefore, a chi-
square test will yield 80% power to detect a clinically important difference of 10% between study groups 
(SOC proportion of 18% vs. PICO NPWT proportion of 8%, an odds ratio of 0.396) when the sample size 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
26 
in each group is 180 evaluable subjects.  Assuming an attrition rate of about 10%, we would need to 
recruit about 200 subjects per group (180/0.90=200 subjects). 
 
Note: A study participant is considered ‘evaluable’ if she has completed all phases of the study including 
the last visit of the last scheduled procedure in the schedule of activities, i.e. the final study visit 4—day 
4210 days post-op. 
 
 
 
9.3 
POPULATIONS FOR ANALYSES 
 
The primary statistical analysis will be based on a modified intention-to-treat (participants who 
underwent surgery and received the intervention). All subjects will be analyzed according to the 
intention-to-treat [ITT] principle.  A patient will be considered evaluable and will be included in the 
intention-to-treat analysis if the patient has completed all phases of the study including the last visit of 
the last scheduled procedure in the schedule of activities, i.e. the final study visit 4—day 4210 days 
post-op.  Analyses that take into account the actual treatment received (e.g. use of PICO NPWT dressing 
for a minimum 5 days) will be carried out as a secondary analysis (per protocol [PP] analysis).  
 
This was chosen to avoid various misleading artifacts that can arise in intervention research such as non-
random attrition of participants from the study or crossover. Subjects strayed from the protocol (for 
instance, by not adhering to the prescribed timing of intervention, or by withdrawing from the study) 
will still be analyzed in the group to which they were assigned. We want to estimate the effects of using 
a PICO dressing at all in practice, not the effects in the subgroup of the participants who adhere to it. If 
patients receive a different type of dressing (intervention) accidentally from the one they were assigned, 
they will be excluded from the study in order to remove any bias that could arise from reasons why a 
provider chose to use that specific dressing instead of the assigned dressing.  
 
In addition, a per-protocol analysis dataset will be analyzed (entire control group and PICO group who 
used the PICO NPWT dressing for a minimum of 5 days.  
 
9.4 
STATISTICAL ANALYSES 
 
9.4.1 GENERAL APPROACH 
 
Descriptive statistics (e.g. means, standard deviations or medians and interquartile range for continuous 
data; frequencies and percentages for categorical data) will be calculated for the patients who meet the 
final inclusion/exclusion criteria. 
 
For descriptive purposes, the overall crude estimates of the incidence of any SSO or any SII will be 
calculated.  These incidences will also be expressed per 100 or 1,000 or 10,000 patients. The chi-square 
test or Fisher’s exact test will be used to compare the crude incidence rates of any SSO or any SII 
between study groups (NPWT vs. SOC). 
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
27 
For continuous and ordinal variables, data will be expressed as a median with interquartile range. For 
dichotomous variables, percentages will be calculated. Comparisons will be performed with the Mann-
Whitney test for continuous variables as appropriate. Comparisons of percentages will be performed 
with the Fisher Exact test as appropriate. 
 
The incidence of SSI and SSO per 100 patients between groups will be compared. Risk ratios (RR), 95% 
CIs and p values assuming a 5% significance level will be presented. 
 
For the primary outcome, the number needed to treat and absolute risk reduction will be calculated 
from the RR. While we do not anticipate differences between groups in terms of known or unknown 
prognostic factors because of randomization, adjusted analyses using multivariate logistic regression 
models will be used if any difference in prognostic variables is detected. 
 
Covariates will be prespecified:  
• 
Medical comorbidities 
o Hypertension (pregestational and gestational) 
o Diabetes (pregestational and gestational) 
o HIV 
• 
Smoking status 
• 
Prior cesarean delivery 
• 
Steroid exposure (betamethasone) within 2 weeks of surgery  
• 
Need for preoperative hair removal (particularly shaving) 
 
Checks of assumptions (e.g., normality) underlying statistical procedures will be performed and whether 
any indicated corrective procedures will be applied (e.g., transformation or nonparametric tests). 
 
A mixed model approach (generalized linear mixed model [GLMM]) will be used to examine the 
incidence of SSOs and SIIs (separately) between study groups, and other factors of interest such as 
medical comorbidities (Hypertension, Diabetes, HIV status), smoking status, prior cesarean delivery, 
steroid exposure within 2 weeks of surgery, and need for preoperative hair removal.  Adjusted Incidence 
Rate Ratios [IRR] and their associated confidence intervals will be obtained from this approach.   
If feasible, a sub-analysis will be performed according to the following BMI stratification of the study 
participants: 35 – <40 kg/m2, 40 – <45 kg/m2, 45 – <50 kg/m2, ≥50 kg/m2. 
 
 
9.4.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
 
Primary endpoint: the incidence of postoperative surgical site occurrences (SSOs) post cesarean delivery. 
SSOs include: 
• 
Unanticipated local inflammatory response – measured by redness, tenderness, 
warmth, or induration on exam. This is a binary nominal categorical variable that will be 
measured as a repeated measure.  

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
28 
• 
Prolonged drainage – measured as drainage from surgical skin site ≥3 days from time of 
surgery. This is a binary nominal categorical variable that will be measured as a repeated 
measure. 
• 
Fluid collection – measured as need for skin opening to drain fluid collected (seroma) 
underneath the skin wound. This is a binary nominal categorical variable that will be 
measured as a repeated measure. 
• 
Dehiscence – measured as opening of skin wound ≥ 2mm. This is a binary nominal 
categorical variable that will be measured as a repeated measure. 
• 
Surgical site infection (SSI) - measured by redness, tenderness, warmth, or induration on 
exam with subject fever or purulent drainage. This is a binary nominal categorical 
variable that will be measured as a repeated measure. 
 
The results of statistical procedure(s) will be presented as odds ratios with 95% confidence intervals, and 
number-needed-to-treat. 
 
Missing data will be handled (e.g., type of imputation technique, if any, and provide justification), and 
approach to handling outliers, nonadherence and lost to follow-up by reporting this data as missing (and 
the reason why) and including all available data in the analysis.  
 
 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
 
Secondary endpoint: Incidence rate of surgical incision intervention (SII) post Cesarean delivery. 
Interventions include: 
o Antimicrobials for surgical site infection. This is a binary nominal categorical variable 
that will be measured as a repeated measure. Analysis of this secondary endpoint is 
dependent on findings of primary endpoints. 
o Surgical drainage of the incision. This is a binary nominal categorical variable that will be 
measured as a repeated measure. Analysis of this secondary endpoint is dependent on 
findings of primary endpoints. 
o Surgical incision packing. This is a binary nominal categorical variable that will be 
measured as a repeated measure. Analysis of this secondary endpoint is dependent on 
findings of primary endpoints. 
o  Adjunctive negative pressure therapy (i.e. need for wound vac therapy). This is a binary 
nominal categorical variable that will be measured as a repeated measure. Analysis of 
this secondary endpoint is dependent on findings of primary endpoints. 
o Debridement. This is a binary nominal categorical variable that will be measured as a 
repeated measure. Analysis of this secondary endpoint is dependent on findings of 
primary endpoints. 
▪ 
Re-operation. This is a binary nominal categorical variable that will be measured 
as a repeated measure. Analysis of this secondary endpoint is dependent on 
findings of primary endpoints. 
 
The results of statistical procedure(s) will be presented as odds ratios with 95% confidence intervals, and 
number-needed-to-treat. 
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
29 
Missing data will be handled (e.g., type of imputation technique, if any, and provide justification), and 
approach to handling outliers, nonadherence and lost to follow-up by reporting this data as missing (and 
the reason why) and including all available data in the analysis.  
 
9.4.4 SAFETY ANALYSES 
 
Safety endpoints will be analyzed as summary statistics during treatment.   
 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
 
The following demographic data will be collected for descriptive statistics and will be compared 
between groups using inferential statistics: 
 
• 
Age 
• 
Race 
• 
Ethnicity 
• 
Gravidity/Parity 
• 
Prior Cesarean delivery 
• 
Gestational age (weeks) 
• 
BMI (kg/m^2) 
• 
Indication for cesarean delivery 
• 
Medical comorbidities 
o Hypertension (pregestational and gestational) 
o Diabetes (pregestational and gestational) 
o HIV 
• 
Smoking status 
• 
Steroid exposure (betamethasone) within 2 weeks of surgery  
• 
Need for preoperative hair removal (particularly shaving) 
 
9.4.6 PLANNED INTERIM ANALYSES  
 
There are no planned formal interim analyses. 
 
9.4.7 SUB-GROUP ANALYSES 
 
Sub-group analysis based on demographic data such as age, sex, or race are not warranted. This study 
intervention is only meant for use in a population of reproductive-age women undergoing cesarean 
delivery for this purpose.  
 
Sub-group analysis will be performed by BMI: 35 – 39.9 kg/m2, 40 – 44.9 kg/m2, 45 – 49.9 kg/m2, 50 – 
54.9 kg/m2. 
 
 
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
30 
Data will be collected at baseline, and participants followed up on the first and postoperative day, the 
PICO group will be telephoned on postpartum day 5 or 6, and then at two postpartum visits: the 7 – 14 
day incision check and the 6-week postpartum visit. 
 
9.4.9 EXPLORATORY ANALYSES 
 
Not applicable.  
 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
 
10.1.1 INFORMED CONSENT PROCESS 
 
10.1.1.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 
 
Consent forms describing in detail the study intervention, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting 
intervention/administering study intervention.  The following consent materials are submitted with this 
protocol: 
 
Informed consent document attached to this IRB submission. 
 
Smith & Nephew PICO Patient Information: 
 
https://www.smith-
nephew.com/global/assets/pdf/products/wound/31447%20uk%20pico%20patient%20info%20leaflet.pd
f  
 
 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Consent forms will be Institutional 
Review Board (IRB)-approved and the participant will be asked to read and review the document. The 
investigator will explain the research study to the participant and answer any questions that may arise. 
A verbal explanation will be provided in terms suited to the participant’s comprehension of the 
purposes, procedures, and potential risks of the study and of their rights as research participants.  
Participants will have the opportunity to carefully review the written consent form and ask questions 
prior to signing. The participants should have the opportunity to discuss the study with their family or 
surrogates or think about it prior to agreeing to participate. The participant will sign the informed 
consent document prior to any procedures being done specifically for the study. Participants must be 
informed that participation is voluntary and that they may withdraw from the study at any time, without 
prejudice. A copy of the informed consent document will be given to the participants for their records. 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
31 
The informed consent process will be conducted and documented in the source document (including the 
date), and the form signed, before the participant undergoes any study-specific procedures. The rights 
and welfare of the participants will be protected by emphasizing to them that the quality of their 
medical care will not be adversely affected if they decline to participate in this study. 
 
 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause.  Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to <study participants, investigator, funding agency, 
the Investigational New Drug (IND) or Investigational Device Exemption (IDE) sponsor and regulatory 
authorities>.  If the study is prematurely terminated or suspended, the Principal Investigator (PI) will 
promptly inform study participants, the Institutional Review Board (IRB), and sponsor and will provide 
the reason(s) for the termination or suspension.  Study participants will be contacted, as applicable, and 
be informed of changes to study visit schedule. 
  
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Demonstration of efficacy that would warrant stopping    
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination that the primary endpoint has been met 
• 
Determination of futility 
 
Study may resume once concerns about safety, protocol compliance, and data quality are addressed, 
and satisfy the sponsor, IRB and/or Food and Drug Administration (FDA). 
 
 
 
10.1.3 CONFIDENTIALITY AND PRIVACY  
 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their 
staff, and the sponsor(s) and their interventions. This confidentiality is extended to cover testing of 
biological samples and genetic tests in addition to the clinical information relating to participants. 
Therefore, the study protocol, documentation, data, and all other information generated will be held in 
strict confidence. No information concerning the study or the data will be released to any unauthorized 
third party without prior written approval of the sponsor.  
 
All research activities will be conducted in as private a setting as possible. 
 
The study monitor, other authorized representatives of the sponsor, representatives of the Institutional 
Review Board (IRB), regulatory agencies or pharmaceutical company supplying study product may 
inspect all documents and records required to be maintained by the investigator, including but not 
limited to, medical records (office, clinic, or hospital) and pharmacy records for the participants in this 
study. The clinical study site will permit access to such records. 
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
32 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by the reviewing IRB, Institutional policies, or sponsor requirements. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be transmitted to and stored in the RedCap (Nashville, Tennessee) database.  This will not include the 
participant’s contact or identifying information. Rather, individual participants and their research data 
will be identified by a unique study identification number. The study data entry and study management 
systems used by clinical sites and by research staff will be secured and password protected. At the end 
of the study, all study databases will be de-identified and archived in the RedCap (Nashville, Tennessee) 
database.  
 
This study is not funded by the NIH.  
 
 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA  
 
Not applicable.  
 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
 
Principal Investigator 
Medical Monitor 
Anar Yukhayev, MD 
Gary Goldberg, MD 
Long Island Jewish Medical Center  
Long Island Jewish Medical Center 
270-05 76th Ave, Queens, NY 11040  
270-05 76th Ave, Queens, NY 11040  
718-470-7660 
718-470-7660 
AYukhayev@northwell.edu 
ggoldberg2@northwell.edu 
 
 
10.1.6 SAFETY OVERSIGHT 
 
Safety oversight will not be under the direction of a Data and Safety Monitoring Board (DSMB) because 
this study is minimal risk.  
 
 
10.1.7 CLINICAL MONITORING 
 
Clinical site monitoring is conducted to ensure that the rights and well-being of trial participants are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct of 
the trial is in compliance with the currently approved protocol/amendment(s), with International 
Conference on Harmonisation Good Clinical Practice (ICH GCP), and with applicable regulatory 
requirement(s).  
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
33 
• 
Anar Yukhayev MD and Gary Goldberg MD will conduct on-site monitoring, throughout the 
study, and a targeted or random review of certain data (targeted data verification of endpoint 
and safety and other key data variables). 
• 
The data will be reviewed in aggregate for data safety monitoring every 30 days.  
• 
Independent audits will not be conducted to ensure monitoring practices are performed 
consistently across all participating sites. 
 
 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
 
Quality control (QC) procedures will be implemented beginning with the data entry system and data QC 
checks that will be run on the database will be generated. Any missing data or data anomalies will be 
communicated to the site(s) for clarification/resolution. 
 
Following written Standard Operating Procedures (SOPs), the monitors will verify that the clinical trial is 
conducted and data are generated and biological specimens are collected, documented (recorded), and 
reported in compliance with the protocol, International Conference on Harmonisation Good Clinical 
Practice (ICH GCP), and applicable regulatory requirements (e.g., Good Laboratory Practices (GLP), Good 
Manufacturing Practices (GMP)).  
 
The investigational site will provide direct access to all trial related sites, source data/documents, and 
reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and 
regulatory authorities. 
 
 
10.1.9 DATA HANDLING AND RECORD KEEPING  
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site 
investigator. The investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. 
 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation 
of data.   
 
Hardcopies of the study visit worksheets will be provided for use as source document worksheets for 
recording data for each participant enrolled in the study.  Data recorded in the electronic case report 
form (eCRF) derived from source documents should be consistent with the data recorded on the source 
documents.  
 
Clinical data (including adverse events (AEs), concomitant medications, and expected adverse reactions 
data) and clinical laboratory data will be entered into <specify name of data capture system>, a 21 CFR 
Part 11-compliant data capture system provided by the <specify Data Coordinating Center>. The data 
system includes password protection and internal quality checks, such as automatic range checks, to 
identify data that appear inconsistent, incomplete, or inaccurate. Clinical data will be entered directly 
from the source documents. 
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
34 
10.1.9.2 STUDY RECORDS RETENTION  
 
Study documents should be retained for a minimum of 2 years after the last approval of a marketing 
application in an International Conference on Harminosation (ICH) region and until there are no pending 
or contemplated marketing applications in an ICH region or until at least 2 years have elapsed since the 
formal discontinuation of clinical development of the study intervention. These documents should be 
retained for a longer period, however, if required by local regulations. No records will be destroyed 
without the written consent of the sponsor, if applicable. It is the responsibility of the sponsor to inform 
the investigator when these documents no longer need to be retained. 
 
10.1.10 
PROTOCOL DEVIATIONS  
 
A protocol deviation is any noncompliance with the clinical trial protocol, International Conference on 
Harmonisation Good Clinical Practice (ICH GCP), or Manual of Procedures (MOP) requirements. The 
noncompliance may be either on the part of the participant, the investigator, or the study site staff. As a 
result of deviations, corrective actions are to be developed by the site and implemented promptly.  
 
These practices are consistent with ICH GCP:  
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
• 
5.1 Quality Assurance and Quality Control, section 5.1.1  
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2.  
 
It is the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations within 15 working days of identification of the protocol deviation, or within 15 working days 
of the scheduled protocol-required activity.  All deviations must be addressed in study source 
documents, reported to the IRB.  Protocol deviations must be sent to the reviewing Institutional Review 
Board (IRB) per their policies. The site investigator is responsible for knowing and adhering to the 
reviewing IRB requirements. Further details about the handling of protocol deviations will be included in 
the MOP. 
 
10.1.11 
PUBLICATION AND DATA SHARING POLICY 
 
This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: 
 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the 
published results of NIH funded research. It requires scientists to submit final peer-reviewed journal 
manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for 
publication. 
 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded 
Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As 
such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be 
submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-
reviewed journals.  Data from this study may be requested from other researchers 10 years after the 
completion of the primary endpoint by contacting Anar Yukhayev, MD. 
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
35 
In addition, this study will comply with the NIH Genomic Data Sharing Policy, which applies to all NIH-
funded research that generates large-scale human or non-human genomic data, as well as the use of these 
data for subsequent research. Large-scale data include genome-wide association studies (GWAS), single 
nucleotide polymorphisms (SNP) arrays, and genome sequence, transcriptomic, epigenomic, and gene 
expression data. 
 
 
10.1.12 
CONFLICT OF INTEREST POLICY 
 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical.  Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the design and conduct of this trial.  The study 
leadership in conjunction with Northwell Health has established policies and procedures for all study 
group members to disclose all conflicts of interest and will establish a mechanism for the management 
of all reported dualities of interest. 
 
10.2 ADDITIONAL CONSIDERATIONS 
 
Not applicable. 
 
 
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
36 
10.3 ABBREVIATIONS 
 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
DRE 
Disease-Related Event 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act  
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation  
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ISO 
International Organization for Standardization 
ITT 
Intention-To-Treat 
LSMEANS 
Least-squares Means 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
MSDS 
Material Safety Data Sheet 
NCT 
National Clinical Trial 
NIH  
National Institutes of Health 
NIH IC 
NIH Institute or Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SOA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
37 
UP 
Unanticipated Problem 
US 
United States 
 
 
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
38 
10.4 PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes of IRB-approved versions of the protocol, including a 
description of the change and rationale. A Summary of Changes table for the current amendment is 
located in the Protocol Title Page.  
 
Version 
Date 
Description of 
Change  
Brief Rationale 
v.1.1 
1/12/2018 
Statistical 
Considerations 
 
Please see modifications in attached 
PACHTMAN_RCT_STATREVISE_2018_JAN_11.docx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
39 
 
 
 
 
 
 
 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
40 
11 REFERENCES  
Acosta S, Björck M, Wanhainen A. Negative-pressure wound therapy for prevention and treatment of 
surgical-site infections after vascular surgery. Br J Surg. 2017;104(2):e75-e84. 
American College of Obstetricians and Gynecologists. ACOG practice bulletin no. 120: use of 
prophylactic antibiotics in labor and delivery. Obstet Gynecol. 2011;117(6):1472–83. 
Arul GS, Sonka BJ, Lundy JB, Rickard RF, Jeffery SL. Management of complex abdominal wall defects 
associated with penetrating abdominal trauma. J R Army Med Corps. 2015;161(1):46-52. 
Arvesen K, Nielsen CB, Fogh K. Accelerated wound healing with combined NPWT and IPC: a case series. 
Br J Community Nurs. 2017;22 Suppl 3(Sup3):S41-S45. 
Bilgi A, Zumrut Biber Muftuler F, Akman L, et al. Negative Pressure Wound Therapy for Patients With 
Complex Abdominal Wounds. Wounds. 2017;29(7):209-214. 
De Vries FE, Wallert ED, Solomkin JS, et al. A systematic review and meta-analysis including GRADE 
qualification of the risk of surgical site infections after prophylactic negative pressure wound therapy 
compared with conventional dressings in clean and contaminated surgery. Medicine (Baltimore). 
2016;95(36):e4673. 
Echebiri NC, McDoom MM, Aalto MM, Fauntleroy J, Nagappan N, Barnabei VM. Prophylactic use of 
negative pressure wound therapy after cesarean delivery. Obstet Gynecol. 2015;125(2):299-307. doi: 
10.1097/AOG.0000000000000634. PubMed PMID: 25569006. 
Fitzwater JL, Tita AT. Prevention and management of cesarean wound infection. Obstet Gynecol Clin 
North Am 2014;41:671–89. 
Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999-
2008. JAMA 2010;303:235–41. 
Gillespie BM. Prophylactic Use of Negative Pressure Wound Therapy After Cesarean Delivery. Obstet 
Gynecol. 2015;126(1):214. doi: 10.1097/AOG.0000000000000937. PubMed PMID: 26241279. 
Glass GE, Murphy GRF, Nanchahal J. Does negative-pressure wound therapy influence subjacent 
bacterial growth? A systematic review. J Plast Reconstr Aesthet Surg. 2017;70(8):1028-1037. 
Grauhan O et al. Prevention of poststernotomy wound infections in obese patients by negative pressure 
wound therapy. The Journal of Thoracic and Cardiovascular Surgery, 2012: 145(5), 1387–92. 
doi:10.1016/j.jtcvs.2012.09.040. 
Harris, J., et al. Using a multi-faceted active process and infection prevention to reduce post-op C-
section infections. Poster presented at SAWC Spring 2013. 
Jenks PJ et al., Clinical and economic burden of surgical site infection (SSI) and predicted financial 
consequences of elimination of SSI from an English hospital Journal of Hospital Infection 86 (2014) 
24e33 
Joyce A. Martin, M.P.H.; Brady E. Hamilton, Ph.D.; Michelle J.K. Osterman, M.H.S.; Anne K. Driscoll, 
Ph.D.; and T.J. Mathews, M.S. Births: Final Data for 2015, National Vital Statistics Reports, Vol. 66, No. 1, 
January 5, 2017.  

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
41 
Karlakki, S., Brem, M., Giannini, S., Khanduja, V., Stannard, J., and Martin, R. Negative pressure wound 
therapy for management of the surgical incisions in orthopaedic surgery. BJR. 2013. 
Lee K, Murphy PB, Ingves MV, et al. Randomized clinical trial of negative pressure wound therapy for 
high-risk groin wounds in lower extremity revascularization. J Vasc Surg. 2017. 
Leth RA, Uldbjerg N, Norgaard M, Moller JK, Thomsen RW. Obesity, diabetes, and the risk of infections 
diagnosed in hospital and post-discharge infections after cesarean section: a prospective cohort study. 
Acta Obstet Gynecol Scand 2011;90:501–9. 
Maurya S, Bhandari PS. Negative Pressure Wound Therapy in the Management of Combat Wounds: A 
Critical Review. Adv Wound Care (New Rochelle). 2016;5(9):379-389. 
Murphy P, Lee K, Dubois L, DeRose G, Forbes T, Power A. Negative pressure wound therapy for high-risk 
wounds in lower extremity revascularization: study protocol for a randomized controlled trial. Trials. 
2015;16:504. 
Olsen MA, Butler AM, Willers DM, et al. Risk factors for surgical site infection after low transverse 
cesarean section. Infect Control Hosp Epidemiol. 2008;29(6):477–84. 
O'Leary DP, Peirce C, Anglim B, et al. Prophylactic Negative Pressure Dressing Use in Closed Laparotomy 
Wounds Following Abdominal Operations: A Randomized, Controlled, Open-label Trial: The P.I.C.O. Trial. 
Ann Surg. 2017;265(6):1082-1086. 
Payne C, Edwards D. Application of the Single Use Negative Pressure Wound Therapy Device (PICO) on a 
Heterogeneous Group of Surgical and Traumatic Wounds. Eplasty. 2014;14:e20. 
Peinemann F. [Negative Pressure Wound Therapy: Randomised Controlled Trials from 2000 to 2015]. 
Zentralbl Chir. 2017;142(3):267-274. 
Raimond E, Pelissier A, Etienette Emeriau M, François C, Graesslin O. Use of negative pressure wound 
therapy after vulvar carcinoma: case studies. J Wound Care. 2017;26(2):72-74. 
Sandy-Hodgetts K, Leslie GD, Parsons R, Zeps N, Carville K. Prevention of postsurgical wound dehiscence 
after abdominal surgery with NPWT: a multicentre randomised controlled trial protocol. J Wound Care. 
2017;26(Sup2):S23-S26. 
Sandy-Hodgetts K, Watts R. Effectiveness of negative pressure wound therapy/closed incision 
management in the prevention of post-surgical wound complications: a systematic review and meta-
analysis. JBI Database System Rev Implement Rep. 2015;13(1):253-303. 
Sarsam SE, Elliott JP, Lam GK. Management of wound complications from cesarean delivery. Obstet 
Gynecol Surv 2005;60:462–73. 
Searle RJ, Myers D. A survey of caesarean section surgical site infections with PICO™ Single Use Negative 
Pressure Wound Therapy System in high-risk patients in England and Ireland. J Hosp Infect. 
2017;97(2):122-124. 
Smid MC, Dotters-Katz SK, Grace M, Wright ST, Villers MS, Hardy-Fairbanks A, et al. Prophylactic 
Negative Pressure Wound Therapy for Obese Women After Cesarean Delivery: A Systematic Review and 
Meta-analysis. Obstet Gynecol. 2017. Epub 2017/10/06. 

PICO NEGATIVE PRESSURE WOUND THERAPY IN OBESE WOMEN UNDERGOING ELECTIVE CESAREAN DELIVERY  
Version 2.1 
Protocol 17-0843 
21 July 2021 
NIH-FDA Clinical Trial Protocol Template – 16 Jan 2018 
 
42 
Stannard JP et al., Use of negative pressure wound therapy over clean, closed surgical incisions. Int 
Wound J 9(Suppl 1): 2012; 32–9. 
Stannard JP et al., Negative pressure wound therapy to treat hematomas and surgical incisions following 
high-energy trauma. J Trauma; 2006: 60:1301–6. 
Strugala V, Martin R. Meta-Analysis of Comparative Trials Evaluating a Prophylactic Single-Use Negative 
Pressure Wound Therapy System for the Prevention of Surgical Site Complications. Surg Infect (Larchmt). 
2017;18(7):810-819. 
Tita AT, Szychowski JM, Boggess K, et al. Adjunctive Azithromycin prophylaxis for cesarean delivery. N 
Engl J Med. 2016;375(13):1231–41.  
Wang Z, Bai M, Long X, Zhao R, Wang X. Negative Pressure Wound Therapy for Patients With Complex 
Abdominal Wounds. Wounds. 2017;29(7):202-208. 
Wloch C et al. Risk factors for surgical site infection following caesarean section in England: results from 
a multicentre cohort study. BJOG 2012;119:1324–33. 
Wolvos TA. Negative pressure wound therapy with instillation: the current state of the art. Surg Technol 
Int. 2014;24:53-62. 
Yu L, Kronen RJ, Simon LE, Stoll CRT, Colditz GA, Tuuli MG. Prophylactic negative-pressure wound 
therapy after cesarean is associated with reduced risk of surgical site infection: a systematic review and 
meta-analysis. Am J Obstet Gynecol. 2017. Epub 2017/09/23.