Prophylactic Sub-lay Non-absorbable Mesh Following Midline Laparotomy: PROMETHEUS (PROphylactic Mesh Trial Evaluation UltraSound)

Study Overview
=================
Brief Summary
-----------------
The aim of the present study is to analyse feasibility, safety and Incisional Hernia rate using a prophylactic sub lay non-absorbable mesh [Parietex Progrip (Medtronic) ] in order to prevent Incisional Hernia following midline emergent laparotomy in clean and clean-contaminated wounds.

Detailed Description
-----------------
The study is a double-blinded randomized trial, comparing the widely recommended midline laparotomy closure using a running slowly absorbable suture to closure with the aid of a permanent sub-lay mesh (Parietex Progrip), in patients undergoing midline laparotomy for clean-contaminated surgery. From January 2016 to June 2018, a series of 200 patients were included. All patients were operated in a single surgical Unit, located in Lacco Ameno (Naples) at the only Hospital of the island. All patients undergoing 'open' midline laparotomy for abdominal surgery in clean-contaminated fields were included. All patients subscribed informed consent. Authorization was requested from the local regional Ethics Committee. Exclusion criteria were: age < 18 years; life expectancy < 24 months (as estimated by the operating surgeon), pregnancy, immunosuppressant therapy within 2 weeks before surgery, clean, contaminated and dirty wounds, wound length<10 cm. Patients were randomized in two groups (Group A, receiving primary closure; Group B, receiving mesh supported closure in a Sublay fashion). Randomization was obtained just before abdominal wall closure through number (1 to 200) extraction by Operative room nurse (Even: Group A vs Odd: Group B). All patients enrolled in the study were followed up sending a letter to their General Practitioner. Outpatient clinic controls were done by surgeons/surgical residents/General Practitioner blinded for the procedure. Technical details Group A. Primary closure of midline laparotomy. The midline fascia is closed using a double layer running slowly absorbable suture. Above arcuate line, the posterior layer was performed suturing peritoneum and posterior rectus sheath; below arcuate line posterior layer was performed suturing peritoneum and trasversalis fascia. Anterior layer was performed suturing anterior rectus sheath. Suture length to wound length ratio of 4:1 as recommended (not routinely measured). Subcutaneous tissue and skin are closed according to the first surgeon's preference. Group B. Sub-lay mesh supported closure A 4 cm space is created between posterior rectus sheath and rectus muscle, widening 2 cm at each side of midline. Both posterior rectus sheath edges are sutured using a running slowly absorbable suture. Above the arcuate line, the posterior layer was performed suturing peritoneum and posterior rectus sheath; below the arcuate line, the posterior layer was performed suturing peritoneum and trasversalis fascia. The anterior layer was performed suturing anterior rectus sheath. A suture length to wound length ratio of 4:1 is recommended (not routinely measured). A 4-cm Parietex Progrip Mesh strip was placed between the posterior rectus sheath and rectus muscle with an overlap of at least 2 cm at each side, sutureless. The not gripping face of the mesh was positioned on the posterior rectal sheat to allow the muscle to become in contact with the grips. In laparotomies >20 cm two stripes of 15 cm each were designed. The midline anterior rectus sheath was closed using a running slowly absorbable suture covering the mesh. A suture length to wound length ratio of 4:1 is recommended (not routinely measured). Subcutaneous tissue and skin closure were up to the surgeon preference. Endpoints Primary endpoint was Incisional Hernia rate. Patients were postoperatively examined at 3, 6, 12 and 24 months. Both clinical examination and ultrasound imaging were performed in all patients at follow-up. Physicians were blind about which Group (A or B) the patients had been placed. Incisional Hernia was clinically defined as any visible or palpable ''blowout'' in the midline abdominal scar. At 3, 6, 12 and 24 months ultrasound imaging was performed to examine the midline for all patients with symptomatic or asymptomatic, providing any valuable information about Incisional Hernia onset. Size and location of all ultrasound detected Incisional Hernia were registered, as well as any other patient's complaint. The ultrasonic criteria of Incisional Hernia were a visible gap within the abdominal wall and/or ''tissue moving through the abdominal wall by Valsalva manoeuvre'' and/or a detectable ''blowout''. Incisional Hernia was diagnosed if clinical criteria and/or ultrasound criteria were fulfilled. The study was not designed to discriminate single or multiple defects. The study will be completed at 2 years' follow up. Secondary endpoints included the incidence of wound events. Wound events were classified as surgical site infections according to Clavien Dindo criteria (superficial, deep or organ space). Surgical site events were reported according to the Ventral Hernia Working Group definitions. Actions for wound events were categorized as follows: antibiotics only, bedside wound interventions, percutaneous manoeuvres or surgical debridement. Blinding Process Patients, care providers, staff collecting data, and those assessing the endpoints were all blinded to treatment allocation. Patients were blinded to the surgical procedure performed until the final assessment of the study endpoints. Because the blinding of the operating surgeons was not feasible, they were not involved in the data collection and outcome assessment. Physicians in charge of patients' management were not involved in the operating room and were blinded to the intervention. The data were collected and analyzed by physicians who were not involved in the patient's management during the whole Randomized trial.

Official Title
-----------------
Prophylactic Sub-lay Non-absorbable Mesh Following Emergent Midline Laparotomy Clean/Contaminated Field: Early Results of a Randomized Double-blind Prospective Trial: PROMETHEUS

Conditions
-----------------
Incisional Hernia, Wound Infection

Intervention / Treatment
-----------------
* Procedure: positioning of polypropylene strips for prophylactic purposes in closing the middle laparotomies to prevent the incisional hernia


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: age > 18 years Clean-contaminated wounds midline laparotomy >10 cm Informed consent Exclusion Criteria: age < 18 years; life expectancy < 24 months (as estimated by the operating surgeon), - pregnancy immunosuppressant therapy within 2 weeks before surgery clean, contaminated and dirty wounds wound length<10 cm.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Sample size: Considering a mean percentage of incidence of Incisional Hernia of 20% in the open middle line laparotomy in the clean-contemned setting. We hypothesized that Incisional Hernia rate in Group B (Experimental Group) would be superior to Group A (control group) if the difference in a mean percentage of incidence of Incisional Hernia was less than 15%. 194 patients are required to have a 90% chance of detecting, as significant at the 5% level, a decrease in the primary outcome measure from 20% in the control group to 5% in the experimental group. Baseline comparisons were performed using chi-square tests and T-tests. Continuous variables are expressed as mean ± standard deviation (SD). Differences between preoperative and postoperative parameters were compared by Wilcoxon paired rank test. For all tests, a two-sided p<0.05 was considered statistically significant. The study designed with Sealed Envelope.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Primary closure<br>Primary closure of midline laparotomy | |
| Experimental: Mesh closure<br>Sub-lay permanent mesh supported the closure | Procedure: positioning of polypropylene strips for prophylactic purposes in closing the middle laparotomies to prevent the incisional hernia<br>* Sub-lay mesh supported closure A 4 cm space is created between posterior rectus sheath and rectus muscle, widening 2 cm at each side of midline. Both posterior rectus sheath edges are sutured using a running slowly absorbable suture. Above arcuate line, posterior layer was performed suturing peritoneum and posterior rectus sheath; below arcuate line, posterior layer was performed suturing peritoneum and trasversalis fascia. Anterior layer was performed suturing anterior rectus sheath. A suture length to wound length ratio of 4:1 is recommended. A 4-cm Parietex Progrip Mesh strip was placed between the posterior rectus sheath and rectus muscle with an overlap of at least 2 cm at each side, suture less. In laparotomies >20 cm two stripes of 15 cm each were designed. The midline anterior rectus sheath was closed using a running slowly absorbable suture, covering the mesh. A suture length to wound length ratio of 4:1 is recommended.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Incisional Hernia at Clinical examination | Clinical examination: Incisional Hernia is clinically defined as any visible or palpable ''blowout'' in the midline abdominal scar | Patients are postoperatively examined at 3 months. | 
| Rate of Incisional Hernia at Clinical examination | Clinical examination: Incisional Hernia is clinically defined as any visible or palpable ''blowout'' in the midline abdominal scar | Patients are postoperatively examined at 6 months. | 
| Rate of Incisional Hernia at Clinical examination | Clinical examination: Incisional Hernia is clinically defined as any visible or palpable ''blowout'' in the midline abdominal scar | Patients are postoperatively examined at 12 months. | 
| Rate of Incisional Hernia at Clinical examination | Clinical examination: Incisional Hernia is clinically defined as any visible or palpable ''blowout'' in the midline abdominal scar. | Patients are postoperatively examined at 24 months. | 
| Rate of Incisional Hernia at Ultrasound examination | Ultrasound imaging is performed to examine the midline for all patients with symptomatic or asymptomatic, providing any valuable information about Incisional Hernia onset. Size and location of all ultrasound detected Incisional Hernia are registered, as well as any other patient's complaint. The ultrasonic criteria of Incisional Hernia are a visible gap within the abdominal wall and/or ''tissue moving through the abdominal wall by Valsalva manoeuvre'' and/or a detectable ''blowout''. Incisional Hernia is diagnosed if clinical criteria and/or ultrasound criteria are fulfilled. | Patients are postoperatively examined at 3 months. | 
| Rate of Incisional Hernia at Ultrasound examination | Ultrasound imaging is performed to examine the midline for all patients with symptomatic or asymptomatic, providing any valuable information about Incisional Hernia onset. Size and location of all ultrasound detected Incisional Hernia are registered, as well as any other patient's complaint. The ultrasonic criteria of Incisional Hernia are a visible gap within the abdominal wall and/or ''tissue moving through the abdominal wall by Valsalva manoeuvre'' and/or a detectable ''blowout''. Incisional Hernia is diagnosed if clinical criteria and/or ultrasound criteria are fulfilled. | Patients are postoperatively examined at 6 months. | 
| Rate of Incisional Hernia at Ultrasound examination | Ultrasound imaging is performed to examine the midline for all patients with symptomatic or asymptomatic, providing any valuable information about Incisional Hernia onset. Size and location of all ultrasound detected Incisional Hernia are registered, as well as any other patient's complaint. The ultrasonic criteria of Incisional Hernia are a visible gap within the abdominal wall and/or ''tissue moving through the abdominal wall by Valsalva manoeuvre'' and/or a detectable ''blowout''. Incisional Hernia is diagnosed if clinical criteria and/or ultrasound criteria are fulfilled. | Patients are postoperatively examined at 12 months. | 
| Rate of Incisional Hernia at Ultrasound examination | Ultrasound imaging is performed to examine the midline for all patients with symptomatic or asymptomatic, providing any valuable information about Incisional Hernia onset. Size and location of all ultrasound detected Incisional Hernia are registered, as well as any other patient's complaint. The ultrasonic criteria of Incisional Hernia are a visible gap within the abdominal wall and/or ''tissue moving through the abdominal wall by Valsalva manoeuvre'' and/or a detectable ''blowout''. Incisional Hernia is diagnosed if clinical criteria and/or ultrasound criteria are fulfilled. | Patients are postoperatively examined at 24 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients affected by Superficial surgical site infections | Superficial infections according to Clavien-Dindo criteria | Within 30 days postoperatively | 
| Number of patients affected by Deep surgical site infections | Deep surgical site infections according to Clavien-Dindo criteria | Within 30 days postoperatively |