Conditions: Ventral Hernia Repair
Keywords: Infection hernia repair
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 250
Healthy volunteers: no

Brief summary:
This is a study to determine if the incidence of infection at the Surgical SitE is impacted if with Antibiotic Irrigation is used during Ventral Hernia Repair (RINSE Trial)

Detailed description:
Surgical site infection (SSI) is common after open ventral hernia repair. Numerous factors contribute, including patient comorbidities, operative technique, and degree of contamination of the case. SSI often requires prolonged hospital length of stay (LOS), readmission, or other procedural intervention. One potential intervention to reduce SSI is the use of antibiotic irrigation, which has been shown to reduce SSI in colorectal surgery in a recent randomized control trial. We retrospectively evaluated our use of dual antibiotic irrigation at the time of mesh placement during open ventral hernia repair (OVHR), demonstrating a significant reduction in SSI (16.5 vs 5.4%) using a combination of gentamicin and clindamycin irrigation when compared to saline alone.

We plan to complete a registry-based, randomized clinical trial (RCT) through the Americas Hernia Society Quality Collaborative (AHSQC) to further assess the impact of dual antibiotic irrigation on SSI after OVHR with mesh. This will include patients undergoing open retromuscular (RM) repair with or without transversus abdominis myofascial advancement flap (TAR) with placement of permanent synthetic mesh (mid-weight, large-pore polypropylene). Power analysis based on only this subset of patients from our initial study indicates a total of 210 patients are needed to demonstrate a significant reduction in SSI using antibiotic irrigation vs saline irrigation alone.

Arms:
arm 1: Normal saline is to be placed into the dissected retromuscular space AFTER placement and fixation of mesh. This should fill the cavity completely to the level of the skin. Irrigant is to be left to stand for a total of three minutes and then evacuated. Additional irrigation with saline PRIOR to the randomization is permitted at the surgeons' discretion for hemostasis with no requirement for duration. Additional saline irrigation of the subcutaneous space after fascia closure should be performed prior to skin closure. arm 2: Antibiotic solution is prepared consisting of 240 mg gentamicin and 600 mg clindamycin in 500 ml saline to ensure proper concentration. This solution should be placed into the dissected retromuscular space AFTER placement and fixation of mesh. This should fill the cavity completely to the level of the skin. Irrigant is to be left to stand for a total of three minutes and then evacuated. Additional irrigation with saline PRIOR to the randomization is permitted at the surgeons' discretion for hemostasis with no requirement for duration. Additional antibiotic irrigation of the subcutaneous space after fascia closure should be performed prior to skin closure. This second irrigation is not timed.

Interventions: intervention 1: Gemcitabine/ clindamycin intervention 2: Normal saline
Intervention descriptions: intervention 1: Comparison of saline solution rinse vs antibiotic rinse intervention 2: Comparison of saline solution rinse vs antibiotic rinse

Protocol document:
Prot_SAP_001.pdf: 
Page 1 of 7 
 
RINSE Study Protocol 
 
NCT Number: NCT03945357  
 
Date: 19Jun2019 
 
Title: Reducing INfection at the Surgical SitE with Antibiotic Irrigation during Ventral Hernia Repair 
(RINSE Trial) 
 
Principal Investigator: 
Jeremy Warren, MD, FACS 
Assistant Professor of Surgery, University of South Carolina School of Medicine Greenville 
Director of Research, Department of Surgery, Prisma Health 
 
Co-Investigators: 
Lily Fatula, MD 
Alfredo Carbonell, DO, FACOS, FACS 
William Cobb, MD, FACS 
 
Abstract: 
Surgical site infection (SSI) is common after open ventral hernia repair. Numerous factors contribute, 
including patient comorbidities, operative technique, and degree of contamination of the case. SSI often 
requires prolonged hospital length of stay (LOS), readmission, or other procedural intervention. One 
potential intervention to reduce SSI is the use of antibiotic irrigation, which has been shown to reduce SSI 
in colorectal surgery in a recent randomized control trial. We retrospectively evaluated our use of dual 
antibiotic irrigation at the time of mesh placement during open ventral hernia repair (OVHR), 
demonstrating a significant reduction in SSI (16.5 vs 5.4%) using a combination of gentamicin and 
clindamycin irrigation when compared to saline alone.  
 
We plan to complete a registry-based, randomized clinical trial (RCT) through the Americas Hernia 
Society Quality Collaborative (AHSQC) to further assess the impact of dual antibiotic irrigation on SSI 
after OVHR with mesh. This will include patients undergoing open retromuscular (RM) repair with or 
without transversus abdominis myofascial advancement flap (TAR) with placement of permanent 
synthetic mesh (mid-weight, large-pore polypropylene). Power analysis based on only this subset of 
patients from our initial study indicates a total of 210 patients are needed to demonstrate a significant 
reduction in SSI using antibiotic irrigation vs saline irrigation alone.  
 
Background and Significance: 
Surgical site infections (SSI) are common complications following open ventral hernia repair (OVHR), 
occurring in 10-60% of cases (1). The frequency of SSIs varies greatly based on operative approach, 
patient co-morbidities, hernia characteristics, and degree of contamination. This may result in 
readmission, increased hospital length of stay (LOS), procedural or operative interventions for infection 
management, or mesh removal, all of which lead to significant patient morbidity and health care 
spending. With over 350,000 ventral hernias repaired annually, reducing the incidence of SSI could have 
a substantial impact on patients and health systems (1, 2). Preoperative patient optimization, including 
preoperative weight loss, smoking cessation, and adequate glucose control, are widely regarded as 
important in minimizing the risk of SSI. Minimally invasive hernia repair also significantly reduces the 
risk of SSI, but not all patients are candidates for this approach.  
 
Interventions performed at the time of surgery, or in selection of materials used for repair are less 
understood. Antimicrobial mesh has shown enhanced bacterial clearance in laboratory testing, but little 


Page 2 of 7 
 
clinical data exists (3-6). Other experimental studies have evaluated pre-soaking or dipping mesh in 
antibiotic solution prior to implantation, but again, clinical data is lacking (7, 8). Antibiotic irrigation of 
the peritoneal cavity was recently shown to have a significant impact on development of SSI in a 
randomized control trial in colorectal surgery. Ruiz-Tovar et al randomized 103 patients to intraperitoneal 
lavage with saline versus clindamycin + gentamicin lavage, demonstrating a significant reduction in 
postoperative SSI from 14% to 4% (9). Historically, we have used simple saline irrigation or gentamicin 
irrigation alone. We adopted the use of clindamycin + gentamicin soon after this report. Our initial 
retrospective analysis of this protocol demonstrates significant benefit of dual-antibiotic irrigation at the 
time of mesh placement in OVHR. We aim to more thoroughly evaluate this outcome with a prospective 
randomized trial. 
 
Preliminary Data: 
We recently published a retrospective evaluation of the impact of antibiotic irrigation at the time of 
OVHR at our institution.  Irrigation with dual-antibiotic solution was performed just after mesh placement 
using 600 mg clindamycin + 240 mg gentamicin in 500 ml saline and was left to stand for a total of three 
minutes as described by Ruiz-Tovar. We analyzed 825 patients undergoing open ventral hernia repair 
with mesh who received either no antibiotic irrigation (Group 1, n=260), gentamicin irrigation (Group 2, 
n=266), or dual antibiotic irrigation with gentamicin + clincamycin (Group 3, n=299). Group 3 contained 
fewer smokers and patients with chronic obstructive pulmonary disease (COPD), but a significantly 
higher proportion of patients with clean-contaminated, contaminated, or dirty cases. Other patient 
characteristics were similar. Retromuscular (RM) repair with or without transversus abdominis release 
(TAR) was performed in 73.2% (n=624), preperitoneal repair in 21.2% (n=181), onlay in 5.1% (n=43) 
and intraperitoneal in 0.5% (n=4). Permanent synthetic mesh was placed in 84.7% of cases, barrier coated 
permanent synthetic in 5.5%, absorbable synthetic in 6.0%, and biologic in 3.8%. Hernias in Group 3 
were larger, with the highest percentage RM and RM+TAR repairs.  
 
Analysis of our primary endpoint demonstrated a significant reduction in the incidence of SSI in patients 
receiving both gentamicin + clindamycin irrigation. Only 5.02% of patients in Group 3 developed an SSI, 
compared to 16.54% in Group 1 and 15.41% in Group 2 (p<0.001). Distribution of infection between 
superficial, deep, and organ space was similar across groups. There was also a significant reduction in 
SSO in with dual antibiotic irrigation, occurring in 19.06% of patients in Group 3, 35.71% of patients in 
Group 2, and 28.08% of patients in Group 1 (p<0.001). The majority of these were simple seromas or 
serous wound drainage, followed by cellulitis, skin separation without infection, and hematoma. Rate of 
SSO/I requiring procedural intervention was significantly higher in Groups 1 & 2 (16.54% & 21.43%) 
than Group 3 (2.68%; p<0.001). No difference was seen in LOS or incidence of readmission between 
groups. Table 3 summarizes primary and secondary outcomes. Multivariate analysis demonstrated that 
COPD (OR 3.70; 95% CI 2.4-6.93), contaminated wound (OR 2.96; 95% CI 1.97-8.17), and dirty wounds 
(OR 3.84; 95% CI 2.93-13.37) were all significant predictors of SSI. Use of dual antibiotic irrigation 
significantly reduced the risk of SSI (OR 0.33; 95% CI 0.14-0.58). 
 
Subgroup analysis of patients undergoing RM repair +/- TAR with permanent synthetic mesh in CDC 
class 1,2 or 3 wounds only demonstrated similar benefits and serve as the basis for this trial. In this 
subgroup comparing only dual antibiotic irrigation (n=224) to saline alone (n=111), antibiotic irrigation 
reduced the rate of SSI in clean (10 vs 3.33%), clean-contaminated (16.67 vs 4%), and contaminated (40 
vs 7.41%) cases.  
 


Page 3 of 7 
 
 
 
 
 
Important limitations of our initial data include selection bias, variation in mesh choice and surgical 
technique, and its retrospective nature. To address these limitations and evaluate the true impact of dual 
antibiotic irrigation at the time of mesh placement during open RM OVHR, we propose a registry based, 
RCT.  
 
Purpose: 
Evaluate the impact of dual antibiotic irrigation at the time of mesh implantation during open VHR.  
 
Hypothesis: 
Use of dual antibiotic irrigation at the time of synthetic mesh placement during open retromuscular 
ventral hernia repair reduces the incidence of surgical site infection. 
 
Study Design: 
The study design would be a registry-based RCT through the AHSQC to evaluate the effect of dual 
antibiotic irrigation at the time of mesh placement during open RM +/-TAR OVHR.  Registry-based trials 
gather information from a pre-existing database to increase the effectiveness of carrying out RCT’s (10). 
A power analysis was performed to determine the needed sample size. For this purpose, dirty (CDC 
wound class 4) patients were excluded (n=51 patients), as SSI rate in this group was significantly higher 


Page 4 of 7 
 
across groups, and the presence of active infection more likely impacts the operative intervention, 
technique, and mesh choice. We included only patients receiving permanent synthetic mesh in a 
retromuscular fashion, with or without TAR. This left 224 patients in the antibiotic irrigation group 
compared to 111 in the saline only irrigation with a difference in SSI of 16.22 vs 4.46%. To detect this 
reduction in SSI with 80% power, a total of 210 patients are needed (105 in each arm). To account for 
20% patient withdrawal or failure to complete 90 day follow-up, we plan to enroll a total of 250 patients 
(125 in each arm).  
 
Inclusion Criteria: 
 
 
Age >18 y/o. 
 
 
Elective, open ventral hernia repair in a retromuscular fashion, with or without TAR. 
 
 
Clean, clean-contaminated, or contaminated wounds. 
 
 
 
Exclusion Criteria: 
 
 
Age <18 y/o. 
 
 
Pregnancy. 
 
 
Emergency hernia repair. 
 
 
Laparoscopic, robotic, or hybrid approach. 
 
 
Dirty wounds. 
 
 
Use of biologic or absorbable synthetic mesh. 
 
 
Onlay, intraperitoneal or preperitoneal mesh placement. 
 
 
 
 
 
In order to achieve enrollment targets and increase the generalizability of the results, data collection will 
be via the AHSQC, a multicenter, national, hernia-specific registry.  The AHSQC includes independently 
audited data, surgeon entered, at each site.  Data is gathered prospectively during routine care for the 
purpose of quality improvement, and the registry also has the capability to host embedded clinical trials.  
All patient demographics, operative details and outcomes data will be collected prospectively from 
participating surgeons and entered into the AHSQC. Randomization will be performed using the Research 
Electronic Data Capture (Redcap) randomization module. To avoid potential variance of wound 
classification between groups, a stratified  contaminated cases in each group. The irrigation used will be 
the only clinical data point collected outside of that already documented in the AHSQC.  There will be a 
total of 8 sites participating in this study, including Greenville Health System, Washington University, 
Cleveland Clinic, Pennsylvania State University, Oregon Health and Science University, Ohio State 
University, New Hanover Regional Medical Center, and University of Pennsylvania. 
 
 
 
Surgical Technique: 
All patients included will undergo an open RM VHR +/-TAR. Preoperative intravenous antibiotics should 
be administered according to local protocol. A midline or other appropriate laparotomy incision will be 
made. Any indicated adhesiolysis will be performed, along with any concurrent procedures. 
Retromuscular dissection will then proceed in standard fashion, separating the posterior rectus sheath 
away from the rectus abdominis muscle laterally to the linea semilunaris. If indicated, additional 
transversus abdominis myofascial release may be performed on one or both sides. Additional 
subcutaneous dissection and/or external oblique myofascial release may be used if deemed necessary by 
the operating surgeon. All patients will receive a mid-weight, large-pore, monofilament polypropylene 
mesh. Acceptable meshes include Prolene soft (Ethicon / Johnson & Johnson), Bard Soft (Bard-Davol, 
Inc), Parietene (Medtronic), or Vitamesh (Aran Biomedical). Mesh fixation is at the discretion of the 
operating surgeon. After mesh is placed, randomization will occur (see below). Drain placement is at the 
discretion of the operating surgeon. Anterior fascia will then be closed over the mesh to complete the 
repair. Skin closure is at the discretion of the surgeon. 
 
 


Page 5 of 7 
 
Randomization: 
Randomization will occur at the time of mesh placement intraoperatively. Redcap will be used to create 
tables to randomly assign patients to either saline irrigation alone (Group 1 – control) or dual antibiotic 
irrigation (Group 2 – study).  
 
Irrigation Protocol: 
Group 1 (control): Normal saline is to be placed into the dissected retromuscular space AFTER placement 
and fixation of mesh. This should fill the cavity completely to the level of the skin. Irrigant is to be left to 
stand for a total of three minutes and then evacuated. Additional irrigation with saline PRIOR to the 
randomization is permitted at the surgeons’ discretion for hemostasis with no requirement for duration. 
Additional saline irrigation of the subcutaneous space after fascia closure should be performed prior to 
skin closure. 
 
Group 2 (study): Antibiotic solution is prepared consisting of 240 mg gentamicin and 600 mg 
clindamycin in 500 ml saline to ensure proper concentration. This solution should be placed into the 
dissected retromuscular space AFTER placement and fixation of mesh. This should fill the cavity 
completely to the level of the skin. Irrigant is to be left to stand for a total of three minutes and then 
evacuated.  Additional irrigation with saline PRIOR to the randomization is permitted at the surgeons’ 
discretion for hemostasis with no requirement for duration. Additional antibiotic irrigation of the 
subcutaneous space after fascia closure should be performed prior to skin closure. This second irrigation 
is not timed. 
 
Both of the groups listed above are accepted standard of care practices used by surgeons. 
 
Follow-up: 
All patients are required to follow-up 30 days (+/- 15 days) from the time of surgery to determine 
incidence of surgical site infection. Additional follow-up will occur at 90 days (+/- 30 days) in office or 
over the phone, with determination of surgical site infection. Additional office visits are at the discretion 
of the surgeon. 
 
Primary Endpoint: 
 
Incidence of surgical site infection (SSI) at 30 days. 
 
 
Secondary Endpoint: 
 
Incidence of SSI requiring reoperation or other procedural intervention at 30 days. 
 
Incidence of SSI at 90 days. 
 
Incidence of SSI requiring procedural intervention (SSIPI) at 90 days. 
 
Incidence of SSO at 30 and 90 days. 
 
Incidence of SSO requiring procedural intervention (SSOPI) at 30 and 90 days). 
 
Incidence of readmission. 
 
Data Collection: 
 
AHSQC data collection. 
 
Redcap database will house the study ID number, date of birth, dates of procedures, AHSQC ID 
number, inclusion/exclusion criteria and randomization module.  We will be collecting protected health 
information (PHI) at each site, which is logged into the AHSQC registry (which all sites already use for 
patients regardless of study).  That data is only available at the local site (i.e. we can see our patients only, 
not patients at other sites).  All data analysis will be done at the AHSQC and no-one will have access to 
any patient level data.  The Redcap data will link to the AHSQC ID, but will not have any other 
identifying information.  All data for this study will be kept confidential. 


Page 6 of 7 
 
 
Potential Risks: 
As with any surgical procedure, there are some associated risks that will be described in a separate 
treatment consent form. 
 
It is possible to have allergic type reactions to the antibiotics used for irrigation.  Allergic reactions may 
range from minor itching or rash to major reactions, even leading to death in rare cases.  However, this is 
not the same as receiving the antibiotics by mouth or through injection in a vein.  Most participants with 
an allergy to the antibiotic taken by mouth or injection will not have a reaction when the antibiotic is 
placed in the irrigation.         
 
The study records are considered confidential, but absolute confidentiality cannot be guaranteed. This 
study may result in presentations and publications, but steps will be taken to make sure participants are 
not identified by name. 
 
Potential Benefits: 
It is not possible to know if there will be any potential benefit beyond what is expected for treatment 
utilizing the standard of care.  Study participation will help us better understand if rinsing the abdominal 
wall and mesh with antibiotic irrigation is any better than irrigating with saline alone in lowering the risk 
of infection after surgery.   
 
Participant Withdrawal: 
Participants may refuse to participate or choose to withdrawal from the study at any time without fear of 
being penalized or losing benefits.  Participants may be withdrawn from the study at any time if it is in the 
study Physician’s judgment that withdrawal is in the participant’s best interest, if the participant’s medical 
condition changes or if the participant no longer follows the study instructions. 
 
Informed Consent: 
The study doctor will assess each patient for eligibility per the protocol. If eligible, the study doctor will 
discuss the study and will review the consent form with the patient and their family (as applicable). The 
study doctor will consent the patient before any study procedures are completed. All communication will 
take place in a private setting. The patient will be given ample time to read the consent and have all 
questions answered prior to providing signature. The consent will be signed and dated by all parties and a 
copy will be provided to the patient at the time of consent. A copy of the consent will also be placed in 
the patient's medical chart.   
 
Alternatives: 
The alternative to participating in this study is simply not to participate. Patients will not be penalized or 
lose any benefits if they decline participation in this study.  This decision will not affect the patient’s 
relationship with his/her doctor or hospital. 
 
Privacy and Confidentiality: 
All data for this study will be kept confidential.  The AHSQC is a secure quality improvement database 
with the purpose to better hernia care delivery.  Likewise, redcap is a password protected, secure network, 
and only approved members of the study team will have access to the study in redcap.   


Page 7 of 7 
 
 
Costs: 
This study is not expected to yield any additional costs to participants.  Participants will not be 
compensated to participate in this study. 
 
Analysis / Data Safety Monitoring: 
A Data Safety Monitoring Board (DSMB) will be established, consisting of a biostatistician and two 
surgeons who are not participants in the trial. Interim analysis will occur at the midpoint of patient accrual 
(125 patients). No events are anticipated that would trigger immediate cessation of the trial. If interim 
analysis demonstrates significantly greater differences in infection than anticipated, the recommendations 
of the DSMB will be followed. 
 
Data analysis will consist of standard statistical methods. Chi square and Fischer’s exact test will be used 
for comparison of patient and operative characteristics. Analysis of variance will be used to determine 
differences in continuous variables. Multivariate logistic regression will be used to test the impact of 
clinically-relevant factors (comorbidities, hernia characteristics, wound class, irrigation). 
 
Potential for Future Study: 
While our experience and initial analysis demonstrates a significant impact of a dual antibiotic irrigation, 
other antibiotic choices or methods of use may have a similar or even greater impact. Many centers 
commonly use a pulse lavage of 3L saline containing cefazolin, bacitracin, and gentamicin. Variation in 
dwell time of the antibiotic irrigation could produce different results. The application of antibiotic 
irrigation to other mesh types may also have a significantly different result.  
 
References  
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Cycle of Complications.Journal of the American College of Surgeons. Elsevier; 2015;221:478–485. 
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case for hernia research.Hernia. 2012;16:179–183. 
3. Harth KC, Rosen MJ, Thatiparti TR, et al. Antibiotic-releasing mesh coating to reduce prosthetic 
sepsis: an in vivo study.J. Surg. Res.; 2010;163:337–343. 
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prosthesis for prevention of surgical mesh infection: experimental study in rats.Hernia. 2015;19:187–194. 
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