A Randomized Controlled Trial of Prevena™ Incisional Negative Pressure Wound Therapy to Reduce Surgical Site Infection in Re-operative Colorectal Surgery
Phase: NA
Conditions: Surgical Site Infection
Sponsor: The Cleveland Clinic

 
Title: A Randomized Controlled Trial of Prevena™ Incisional Negative Pressure Wound Therapy to 
Reduce Surgical Site Infection in Re-operative Colorectal Surgery. 
 
Authors: John Burke, Jean Ashburn, Vicki Rumpler, Luca Stocchi, Feza Remzi. 
 
Institution: Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, 9500 
Euclid Ave, Cleveland, OH, 44195, USA. 
 
Introduction: 
Surgical site infections (SSIs) are a common problem and a significant cause of morbidity in surgical 
patients. They present a substantial burden to the health care system in the United States and 
contribute more than 1.6 billion dollars in excess cost and 1 million in extra hospital days in affected 
patients1. SSIs are associated with a multitude of complications including an increased risk of 
incisional hernia and prolonged hospital stay2. Despite optimum surgical care there remains an 
inability to significantly reduce SSI rates following colorectal surgery and this field represents a 
critical priority for study3. When one examines the control arms of recent high quality randomized 
controlled trials, the SSI rate following colorectal surgery ranges from 22.0-26.1%4-6, emphasizing 
the prevalence of this complication.  
 
Many strategies have been attempted to reduce SSI rates. The Centers for Medicare and Medicaid 
Services introduced the Surgical Care Improvement Project infection project with the aim of 
reducing SSI incidence and morbidity. These measures include prophylactic intravenous antibiotics 
administered within 1 hour of skin incision, appropriate prophylactic antibiotic selection, 
discontinuation of prophylactic antibiotics within 24 hours after surgery, appropriate hair removal, 
and maintenance of perioperative normothermia7. Despite the enforcement of these measures 
through quality reporting and pay-for-performance measures, significant controversy exists as to 
their overall effectiveness8, especially in the high-risk colorectal surgical population9. Laparoscopic 
surgery has been shown to improve SSI rates in the colorectal population10; however, not all 
patients are appropriate candidates for this approach and the inability of promising interventions 
such as wound edge protection6 and gentamicin sponges4 to improve SSI rates following colorectal 
surgery mandate the investigation of novel techniques.  
 
Initiated in the orthopaedic literature, a new technique of wound dressing has been described to 
reduce SSI11. Incisional negative pressure wound therapy (NPWT) using devices such as the 
Prevena™ involves applying a wound vacuum sponge over a standard wound closure (including 
fascial closure and skin closure with staples). The incisional NPWT dressing is then left in place for 
5 to 7 days before removal. A recent retrospective study by Bonds et al. described the ability of 
incisional NPWT to reduce SSI rates in open colorectal surgery from 29.3-12.5%12. 
 
The aim of the current study is to assess the clinical effectiveness of incisional NPWT to reduce SSI 
rates in open, re-operative colorectal surgery. The primary endpoint of this study is the occurrence 
of superficial SSI within 30 days after surgery and the secondary endpoints include, length of 
hospital stay and cost effectiveness. 
 
Methods 
Study design and patients 
This investigator-initiated trial will be a prospective, unicentre, randomized controlled trial. It is 
planned to be conducted from July 2015 to June 2018 at the Department of Colorectal Surgery at 
the Cleveland Clinic, Ohio. However, it is likely given the high volume practice of department, that 

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it will be completed sooner. Patients aged over 18 years undergoing re-operative colorectal surgery 
defined as the excision or revision of a prior anastomosis, intestinal resection with an incisional 
hernia repair or enterocutaneous fistula repair in both elective and emergency settings are eligible 
for enrolment. Patients undergoing completion proctectomy and ileal pouch anal anastomosis with 
a mucous fistula from their rectal stump will also be included. Laparoscopic or laparoscopic assisted 
procedures, patients who had undergone a laparotomy within the preceding three months and an 
active SSI at the time of surgery will be excluded. Institutional review board approval will be sought 
before trial commencement, written informed consent will be obtained from all patients before 
enrolment and the trial will be registered with clinicaltrials.gov. The number and reason of patients 
excluded and lost to follow-up will be prospectively recorded.  
 
Randomization 
Enrolled patients will be randomly assigned through a concealed centralized secure web based 
system in a 1:1 ratio to either the control arm (standard post-operative care) or the intervention 
arm (the application of the Prevena™ NPWT system (Acelity, San Antonio, TX)). Randomization will 
be performed when the patient attends the last preoperative visit using the REDCap™ (Research 
Electronic Data Capture) secure online system. In our department this visit occurs on the day prior 
to surgery, facilitating ease of enrolment.  
 
The departmental SSI prevention bundle will be used in all cases including preoperative mechanical 
bowel preparation with the addition of oral antibiotics, a preoperative patient shower with 
Hibiclens (Mölnlycke Health Care, Norcross, GA), intravenous antibiotics administered 1 hour 
before skin incision, antiseptic preparation of  the abdomen, the routine use of a wound protector, 
surgical glove changes following contamination and before wound closure and separate 
instruments used for wound closure. The non-NPWT dressing will be left in place for 48 hours 
before changing.  
 
Surgeons in the Colo-rectal surgery department trained in the application of the Prevena™ NPWT 
system will enroll and operate on patients included in this trial. All wounds will be irrigated with 
sterile saline before closure and the attending staff surgeon will perform all closures themselves. 
The fascia will be closed with interrupted or running # 1 Maxon™ (Covidien), followed by skin 
closure with staples. Control patients with standard wound dressings will have gauze and tape 
dressings applied while those in the NPWT group will have the Prevena™ system applied; both 
before the maturation of the ostomy to avoid contamination of the wound with enteric content. 
The Prevena™ system will remain in place for 7 + 1 days. However, if concern exists for the patients 
wound, it will be removed, the wound assessed and this will be recorded as a break from trial 
protocol. The Prevena™ will however be reapplied if the wound is not infected. 
 
Efficacy outcomes 
The primary endpoint will be the occurrence of superficial surgical site infection within 30 days 
after the operation. Diagnosis will be based on criteria developed by the Centers for Disease 
Control (CDC)13. All wound assessors will be experienced in the appraisal of postoperative wounds 
and will be provided with standardized criteria and instruction regarding assessment.  
 
Secondary endpoints will include length of hospital stay, cost effectiveness, and the clinical efficacy 
of the device in relation to the degree of contamination, patient comorbidity, and operative 
demographics. This information will be recorded contemporaneously on standardized clinical 

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report forms. Data for this study will then be entered into a REDCap database, which uses a MySQL 
database via a secure web interface with data checks used during data entry to ensure data quality. 
REDCap includes a complete suite of features to support HIPAA compliance, including a full audit 
trail, user-based privileges, and integration with the institutional LDAP server. The MySQL database 
and the web server will both be housed on secure servers operated by the Cleveland Clinic.  
 
Procedures 
Preoperative evaluation will include the prospective assessment and recording of demographic 
data related to the patient and their co-morbidities. Operative details, including any deviation from 
allocation, will be recorded immediately after the operation (Appendix 1). The post-operative 
wound will be assessed daily by the attending staff surgeon. A trained reviewer independent from 
the surgical team performing the interventionwill formally assess the wound on post-operative day 
seven. If the patient is discharged prior to post-operative day 7, an early outpatient assessment 
will be scheduled for day 7 + 1 day as is the standard practice of our department. A second formal 
wound review will be performed at 30 (+/-7) days, which will involve the patient returning to 
hospital for a physical review of the wound. At this same visit, patients will also complete a 
supervised, self-reported post-discharge questionnaire (PDQ) with the study investigator to 
identify any occurrence of SSI during the intervening period between the two clinical assessments. 
The questionnaire is based on the validated Health Protection Agency surgical site infection 
surveillance system6, which is based on the original CDC definitions (Appendix 2) and has been used 
in prior high quality randomized trials of SSIs6. To our knowledge, this will represent the first time 
this questionnaire is used in a trial of Prevena™. On day 7 + 1 day and 30 + 7 days a photograph will 
be taken of the wound to be evaluated by a blinded assessor of wound healing at a later date and 
scored on a modified 10-point Likert scale (1 = very poorly healed; 10 = fully healed). 
 
Cost Analysis 
The objective of the economic evaluation is to explore the relative cost-effectiveness of Prevena™ 
NPWT compared to standard care. Cost and resource use data will be collected prospectively for 
both arms of the trial. Trial co-coordinators will identify hospital utilization items and primary care 
utilization items will be determined by patient interview at the post-operative 30-day clinic visit. 
Unit costs will be valued in $ (2015 value). The cost of the intervention (Prevena™ NPWT) will be 
obtained from the manufacturer. Inpatient care resource items will be sourced from the Cleveland 
Clinic Reference Costs data. Total resource costs will be obtained by summation of the individual 
resource costs for each category of resource item accessed by trial patients. Individual resource 
costs will be obtained by multiplying the resource use by the corresponding unit costs. 
 
Statistical analysis 
We hypothesize that the use of Prevena™ incisional NPWT in adults reduces SSI rates in open, re-
operative colorectal surgery. For re-operative colorectal surgery, the Department of Colorectal 
Surgery at the Cleveland Clinic, Ohio has observed a 19.4% overall SSI rate (unpublished internal 
audit). Assuming a 2.34 fold reduction in SSI rates based on a prior retrospective study in the setting 
of Colorectal Surgery12 (19.4% to 8.3%), 298 patients (149 per control and intervention arm) are 
required to achieve a power of 80% and a two-sided type I error rate of 0.05 (StudySize v3.0, 
CreoStat HB, Gothenburg, Sweden). As there is only one primary endpoint (SSI development), 
adjustments for multiplicity are not required.  
 
Results will be analyzed according to the intention to treat principal. For the primary endpoint, 

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missing data will be handled by the principal of complete-case analysis, thus, participants with 
missing data will be excluded from the analysis. Descriptive statistical comparisons between the 
two study groups will be performed with the use of chi-square tests or Fisher's exact test, as 
appropriate, for categorical end points and analysis-of-variance techniques or Wilcoxon rank-sum 
tests, as appropriate, for continuous end points. The log-rank tests will be used to compare the 
time to first surgical-site infection between the two study groups. Kaplan–Meier survival 
estimates of the time to first surgical-site infection will also calculated. Analyses will be 
performed with SPSS version 20.0 (IBM Corp, Armonk, NY, USA). P<0.05 will be considered 
statistically significant. A formal, interim analysis is planned to take place when a total of one 
hundred patients have been accrued for both arms all together. 

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References 
 
 
1. 
de Lissovoy G, Fraeman K, Hutchins V, et al: Surgical site infection: incidence and 
impact on hospital utilization and treatment costs. Am J Infect Control 37:387-97, 2009 
 
2. 
Murray BW, Cipher DJ, Pham T, et al: The impact of surgical site infection on the 
development of incisional hernia and small bowel obstruction in colorectal surgery. Am J Surg 
202:558-60, 2011 
 
3. 
Burke JP, O'Connell PR: Surgical site infection and colorectal surgery: a research 
priority. Dis Colon Rectum 57:e390, 2014 
 
4. 
Bennett-Guerrero E, Pappas TN, Koltun WA, et al: Gentamicin-collagen sponge for 
infection prophylaxis in colorectal surgery. N Engl J Med 363:1038-49, 2010 
 
5. 
Darouiche RO, Wall MJ, Jr., Itani KM, et al: Chlorhexidine-Alcohol versus Povidone-
Iodine for Surgical-Site Antisepsis. N Engl J Med 362:18-26, 2010 
 
6. 
Pinkney TD, Calvert M, Bartlett DC, et al: Impact of wound edge protection devices 
on surgical site infection after laparotomy: multicentre randomised controlled trial (ROSSINI 
Trial). BMJ 347:f4305, 2013 
 
7. 
Hendren S, Fritze D, Banerjee M, et al: Antibiotic choice is independently 
associated with risk of surgical site infection after colectomy: a population-based cohort study. 
Ann Surg 257:469-75, 2013 
 
8. 
Stulberg JJ, Delaney CP, Neuhauser DV, et al: Adherence to surgical care 
improvement project measures and the association with postoperative infections. JAMA 
303:2479-85, 2010 
 
9. 
Pastor C, Artinyan A, Varma MG, et al: An increase in compliance with the Surgical 
Care Improvement Project measures does not prevent surgical site infection in colorectal surgery. 
Dis Colon Rectum 53:24-30, 2010 
 
10. 
Schwenk W, Haase O, Neudecker J, et al: Short term benefits for laparoscopic 
colorectal resection. Cochrane Database Syst Rev:CD003145, 2005 
 
11. 
Gomoll AH, Lin A, Harris MB: Incisional vacuum-assisted closure therapy. J Orthop 
Trauma 20:705-9, 2006 
 
12. 
Bonds AM, Novick TK, Dietert JB, et al: Incisional negative pressure wound therapy 
significantly reduces surgical site infection in open colorectal surgery. Dis Colon Rectum 56:1403-
8, 2013 
 
13. 
Horan TC, Andrus M, Dudeck MA: CDC/NHSN surveillance definition of health care-
associated infection and criteria for specific types of infections in the acute care setting. Am J 
Infect Control 36:309-32, 2008 
 
14. 
Dindo D, Demartines N, Clavien PA: Classification of surgical complications: a new 
proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205-
13, 2004 
 

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Appendix 1: Perioperative clinical variables recorded. 
 
Pre-operative Factors 
Age 
Sex 
Body mass index (Kg/M2) 
Charleson co-morbidity index 
Diabetic 
Current smoker 
Chronic kidney disease 
Medications: 
-Steroids 
-Immunosuppressants 
Preoperative serum albumin 
Pathology 
-Malignancy 
-Inflammatory bowel disease 
-Other benign 
ASA grade (1-4) 
Urgency of operation: 
-Elective 
-Urgent 
-Emergent 
Procedure performed 
Intra-operative 
Skin preparation used: 
-Chlorhexidine 
-Aqueous povidone-iodine 
-Alcoholic povidone-iodine 
Duration of Surgery (minutes) 
Prophylactic antibiotics given: 
-Before induction 
-During procedure 
Degree of contamination: 
1. Clean 
2. Clean-contaminated 
3. Contaminated 
4. Dirty 
Operation site: 
-Large bowel 
-Small bowel 
-Both 
Ostomy: 
-Ileostomy 
-Colostomy 
Mesh used for a hernia? If so, type? 

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Blood loss (mL) 
Wound length (cm) 
Number of staples used to close the wound 
Type of Prevena used (peel & place Vs customizable)  
Post-operative 
Overall post-operative complications (Clavien-Dindo Grade14) 
Removal of VAC early? If so, for what reason? 
VAC leakage 
Peri-operative transfusion 
Surgical site infection: 
1-Superficial 
2-Deep 
3-Organ space 
-If so, occurred on which day? 
Procedures undertaken for SSI: 
-Opening of wound  
-Opening the wound and packing 
-Exploration of the wound under general anesthesia 
-Application of a vacuum dressing  
-Oral antibiotics 
-Intravenous antibiotics 
Wound healing Likert Score (1-10) from wound photographs 
taken on post-operative day 0, 7 and 30 
 

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Appendix 2: Patient post-discharge questionnaire (PDQ)  
 
Please complete the following questionnaire: 
 
Please fill in the date you completed this questionnaire ____/____/____  
Have you had any problems with the healing of your wound?  YES NO  
 
If you have answered NO you do not need to continue with the rest of the form. Thank you for taking the time to do this. If you 
have answered YES, please read the following carefully and complete the rest of the form.  
 
Since you were discharged from hospital after your operation, have you noticed any of the following symptoms?  
 
Was there any discharge or leakage of fluid from any part of the wound? Yes No 
If yes, was it either;  
Clear or blood stained 
 Yellow/green (pus) 
Other-please specify  
 
Please tick any of the following additional symptoms that applied to your wound:  
 Pain or soreness in addition to the discomfort experienced following the operation.  
Redness or inflammation spreading from the edges of the wound. 
The area around the wound felt warmer/hotter than the surrounding skin. 
The area around the wound became swollen  
 The edges of any part of the wound separated or gaped open. 
 
Did any health care worker take a sample from your wound to send to the laboratory?  
Yes No  
 
If you saw a health care worker because of these symptoms, please indicate who you saw from the list below-  
Primary care physician 
Home care nurse 
Doctor or nurse at the hospital  
Other – please specify 
 Did not see one about my wound  
 
Please tell us the date you noticed these symptoms. If you cannot remember the exact date, please give an approximate date 
_____/____/_____  
 
Have you been prescribed antibiotics for an infection in the wound?  
Yes No 
If yes, who prescribed them? __________________________________________  
 
Have you been re-admitted to hospital with an infection of the surgical wound?  
To the hospital at which the operation was carried out?  Yes  No  
To another hospital?  Yes  No  
If yes, which one? _________________________________  
Other comments__________________________________________________________  
 
 
To be complete by the trial investigator 
Patient reported SSI meets definition  Yes  No  
 
If yes enter criteria for SSI: 
Criterion 1: Discharge pus + antibiotics prescribed Clinical signs* + dehiscence 
Criterion 2: Clinical signs* + antibiotics prescribed 
Criterion 3: Clinical signs* + antibiotics prescribed