Polihexanide SSIs Measures Bundle (PSMB) During Enhanced Recovery After Major Digestive Surgery (POSSIBLE)

This is a randomized controlled, prospective, multicenter superiority trial with two parallel treatment groups and single blinding (local investigators performing postoperative follow up will be blinded for group allocation), with prospective enrollment planned from July 2024 to June 2025 in 20 Italian surgical centers. All patients undergoing elective major gastro-intestinal (GI) tract surgery (upper GI, HPB, & lower GI) will be included in a prospective database after written informed consent. A total of 2,000 patients is expected based on a mean of 100 cases per center.

Study Overview

• Status: Not yet recruiting
• Conditions: Surgical Site Infection; Surgical Procedures, Operative
• Intervention / Treatment: Combination product: Polihexanide-based bundle; Combination product: Standard bundle

Detailed Description

Just after signing a written informed consent to participate, patients will randomly be assigned either to the experimental group (Polihexanide bundle) or to the control group. Block randomization (blocks of 10 patients per single participating center) will be performed using an unstratified computer generated randomization list. All operations will be performed according to local criteria of the participating center. Hair removal will be accomplished on the day of surgery with electronic clippers. Alcohol-based solutions of chlorhexidine for surgical site skin preparation will be used. A first dose of perioperative i.v. antibiotics will be administered 30 minutes before skin incision (choice of the antibiotic according to local criteria) in all patients. Additional intraoperative doses will be administered for procedures exceeding two half-lives of the antibiotic. At the end of the operation, the peritoneal cavity will be rinsed routinely with 0.9% sodium chloride solution (normal saline, NS) at body temperature. Before closure of fascia, instruments and gloves will be changed. The eventual placement of drain(s) in the peritoneal cavity and/or creation of an intestinal stoma will be recorded. No subcutaneous suture or drainage will be done. Skin will be closed with either staples, intracutaneous running suture or interrupted sutures.

Potential patient-specific and intraoperative risk factors will be recorded: sex, age, body mass index, nutritional status, frailty, indication to surgery (benign vs. malignant disease), perioperative administration of steroids, renal failure and dialysis, cardiovascular or respiratory disease, American Society of Anesthesiologist class, bowel preparation, type of approach, operative time, presence of peritoneal cavity drainage. During the postoperative period, patients will be examined by the attending surgeon daily. Fever (central temperature > 38 °C), pulse, abdominal signs, bowel movements, volume and aspect of drainage (if present) will be recorded daily. The local attending surgeon will make any decision for complementary exams and imaging according to his own criteria. The rate of any adverse event will be calculated and graded according to the Clavien-Dindo criteria [19] and to Japan Clinical Oncology Group Postoperative Complications (JCOG-PC) extended criteria [20], including all anastomotic leaks, wound infection (according to the definitions of the Centers for Disease Control and Prevention and wound culture), pneumonia (clinical symptoms, and physical and radiological examinations), central venous line infection (positive blood culture), urinary tract infection (positive urine culture with bacterial count). ERAS pathway items will be defined according to national [27] guidelines, measuring adherence upon explicit criteria. All data will be recorded for a minimum of 8 weeks (60 days) after surgery. PROM questionnaires will be administered to all enrolled patients four to one week before the planned operation, at discharge, and 6 to 8 weeks after the operation.

After anonymization, all data of each single case will be prospectively uploaded by local investigator(s) on a web-based database, protected by individual access credentials, and incorporated into a spreadsheet for data analysis. Any eventual discrepancy and/or mismatch will be checked, addressed and solved through strict cooperation between coordinating and local investigators.

• Study Type: Interventional
• Enrollment (Estimated): 2000
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Marco Scatizzi, MD; Phone Number: +393492197687; Email: marcoscatizzi60@gmail.com
• Study Contact Backup: Name: Mario Campli, MD; Phone Number: +393939038353; Email: segreteria@acoi.it

Study Locations

• Italy
  • FI
    • Firenze, FI, Italy, 50012
      • Ospedale Santa Maria Annunziata
      • Contact: Marco Scatizzi, MD; Phone Number: 393474137246; Email: marcoscatizzi@gmail.com
  • MC
    • Macerata, MC, Italy, 62100
      • Ospedale Civile di Macerata
      • Contact: Massimo Sartelli, MD; Phone Number: +393405369701; Email: massimosartelli@gmail.com
  • RM
    • Roma, RM, Italy, 00157
      • Ospedale Sandro Pertini
      • Sub-Investigator: Paolo Ciano, MD
      • Contact: Marco Catarci, MD; Phone Number: +393298610040; Email: marco.catarci@aslroma2.it
      • Sub-Investigator: Michele Benedetti, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients submitted to laparoscopic/robotic/open/converted major digestive surgery (upper and lower gastrointestinal resections).
• American Society of Anesthesiologists' (ASA) class I, II, III or IV
• Elective surgery
• Patients' written acceptance to be included in the study.

Exclusion Criteria:

• American Society of Anesthesiologists' (ASA) class V
• Urgent surgery
• Pregnancy
• Hyperthermic intraperitoneal chemotherapy for carcinomatosis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Once a day starting 5 days before the operation: Total body washing with usual soap/shampoo and single-use washcloths impregnated with a mix of Polihexanide, surfactants, and excipients. Nasal cleaning 3 times a day with a Polihexanide Nasal Gel Oral gargles 3 times a day using 10 mL of a Polihexanide oral solution. After the closure of fascia, 10 minutes subcutaneous irrigation with 50 to 250 mL (according to incision length) of antiseptic solution will be performed using a 0.04% sterile Polihexanide solution. After the end of the application time, a subcutaneous swab for culture will be taken. Before standard (according to local center clinical practice) wound(s) dressing(s), a 3 mm-thick antiseptic gel (a combination comprised of 0.1 % Polihexanide and 0.1 % propyl betaine (surfactant) that is used for cleansing, moistening and decontamination of post-operative wounds) will be applied on any wound(s).	Combination product: Polihexanide-based bundle; Pre- and intra-operative decontamination will be accomplished in the treatment (experimental) arm with Polihexanide-based products; Other Names: Prontoderm® Wipes (B. Braun Medical AG, Sempach, Switzerland); Prontoderm® Nasal Gel (B. Braun Medical AG, Sempach, Switzerland); ProntOral® (B. Braun Medical AG, Sempach, Switzerland); LavaSurge® (B. Braun Medical AG, Sempach, Switzerland)
Active Comparator: Control; Once a day starting 5 days before the operation: Total body washing with usual soap/shampoo. No oral and nasal MDRO-decolonization will be performed. After the closure of fascia, 10 minutes subcutaneous irrigation with 50 to 250 mL (according to incision length) NS will be performed. After the end of the application time, a subcutaneous swab for culture will be taken. Finally, standard wound(s) dressing(s) (according to local center clinical practice) will be applied.	Combination product: Standard bundle; Pre- and intra-operative decontamination will be accomplished in the control arm with normal soap/shampoo and saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgical Site Infections rate	CDC definition	60 days after surgery
Incisional (superficial and deep) Surgical Site Infections rate	CDC definition	60 days after surgery
Infectious morbidity rates	SSI + urinary tract infection + pulmonary infection	60 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anastomotic leakage rates	According to international consensus	60 days after surgery
Overall morbidity rates	Any adverse event	60 days after surgery
Major morbidity rates	Any adverse event grade > II according to Clavien-Dindo	60 days after surgery
Comprehensive complication index	According to Slankamenac et al 2013	60 days after surgery
Overall length of postoperative hospital stay	inclusive of any unplanned readmission	60 days after surgery
Readmission rates	any unplanned readmission after primary discharge	60 days after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported outcome measures	MD Anderson Symptom Inventory for Gastrointestinal Surgery	preoperative, at discharge, 60 days after surgery

Collaborators and Investigators

• Sponsor: Marco Catarci
• Collaborators: Associazione Chirurghi Ospedalieri Italiani
• Investigators: Study Chair: Marco Catarci, MD, FACS, Associazione Chirurghi Ospedalieri Italiani; Principal Investigator: Massimo Sartelli, MD, Ospedale Di Macerata

Publications and helpful links

General Publications

• Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibanes E, Pekolj J, Slankamenac K, Bassi C, Graf R, Vonlanthen R, Padbury R, Cameron JL, Makuuchi M. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009 Aug;250(2):187-96. doi: 10.1097/SLA.0b013e3181b13ca2.
• Katayama H, Kurokawa Y, Nakamura K, Ito H, Kanemitsu Y, Masuda N, Tsubosa Y, Satoh T, Yokomizo A, Fukuda H, Sasako M. Extended Clavien-Dindo classification of surgical complications: Japan Clinical Oncology Group postoperative complications criteria. Surg Today. 2016 Jun;46(6):668-85. doi: 10.1007/s00595-015-1236-x. Epub 2015 Aug 20.
• Berrios-Torres SI, Umscheid CA, Bratzler DW, Leas B, Stone EC, Kelz RR, Reinke CE, Morgan S, Solomkin JS, Mazuski JE, Dellinger EP, Itani KMF, Berbari EF, Segreti J, Parvizi J, Blanchard J, Allen G, Kluytmans JAJW, Donlan R, Schecter WP; Healthcare Infection Control Practices Advisory Committee. Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection, 2017. JAMA Surg. 2017 Aug 1;152(8):784-791. doi: 10.1001/jamasurg.2017.0904. Erratum In: JAMA Surg. 2017 Aug 1;152(8):803.
• Rahbari NN, Weitz J, Hohenberger W, Heald RJ, Moran B, Ulrich A, Holm T, Wong WD, Tiret E, Moriya Y, Laurberg S, den Dulk M, van de Velde C, Buchler MW. Definition and grading of anastomotic leakage following anterior resection of the rectum: a proposal by the International Study Group of Rectal Cancer. Surgery. 2010 Mar;147(3):339-51. doi: 10.1016/j.surg.2009.10.012. Epub 2009 Dec 11.
• Mueller TC, Loos M, Haller B, Mihaljevic AL, Nitsche U, Wilhelm D, Friess H, Kleeff J, Bader FG. Intra-operative wound irrigation to reduce surgical site infections after abdominal surgery: a systematic review and meta-analysis. Langenbecks Arch Surg. 2015 Feb;400(2):167-81. doi: 10.1007/s00423-015-1279-x. Epub 2015 Feb 14.
• Strobel RM, Leonhardt M, Krochmann A, Neumann K, Speichinger F, Hartmann L, Lee LD, Beyer K, Daum S, Kreis ME, Lauscher JC. Reduction of Postoperative Wound Infections by Antiseptica (RECIPE)?: A Randomized Controlled Trial. Ann Surg. 2020 Jul;272(1):55-64. doi: 10.1097/SLA.0000000000003645.
• Allegranzi B, Bischoff P, de Jonge S, Kubilay NZ, Zayed B, Gomes SM, Abbas M, Atema JJ, Gans S, van Rijen M, Boermeester MA, Egger M, Kluytmans J, Pittet D, Solomkin JS; WHO Guidelines Development Group. New WHO recommendations on preoperative measures for surgical site infection prevention: an evidence-based global perspective. Lancet Infect Dis. 2016 Dec;16(12):e276-e287. doi: 10.1016/S1473-3099(16)30398-X. Epub 2016 Nov 2.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: March 23, 2024
• First Submitted That Met QC Criteria: March 28, 2024
• First Posted (Actual): March 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: surgical site infection; polihexanide; preoperative decontamination
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Postoperative Complications; Wound Infection; Surgical Wound Infection; Anti-Infective Agents; Disinfectants; Polihexanide
• Other Study ID Numbers: POSSIBLE 1.6

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: complete dataset after study completion will be availble upon request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No