Randomized Controlled Trial to Evaluate the Optimal Timing of Surgical Antimicrobial Prophylaxis

NCT01790529 | Completed Phase 4 DMC

• 1 other identifier: SSI-19/12
• Study Type: interventional
• Target: 5,000
• Locations: 1 country
• Sites: 1

Brief Summary

Surgical site infections (SSI) are the most frequent hospital acquired infections in patients who underwent surgery. With regards to the increasing financial restraint in patient care, the socio-economic burden of SSI in the public health sector and its prevention gains in importance. The prophylactic application of antibiotics (surgical antimicrobial prophylaxis, SAP) prior to the skin incision significantly reduces the risk of SSI, but the correct time point of drug administration remains unclear. Most studies recommend application of SAP directly prior to skin incision. Other studies, however, suggest that this is too late and more time between administration of the SAP and skin incision is necessary for optimal SSI prevention. A large cohort study in Switzerland concluded that SAP should be applied between 74 and 30 minutes prior to skin incision. Due to the obvious importance of this controversy, we want to answer this question with a clinical study (randomized controlled trial, RCT) at the University Hospital of Basel and the Cantonal Hospital of Aarau. We plan to investigate two administration strategies according to the timing of the SAP. Strategy A will consist of SAP application in the anesthetic room located in front of the actual operating theatre, where the patient gets anesthesia. Therefore, the application of SAP will take place early, approximately between 75 and 30 minutes prior to skin incision. In strategy B we will apply SAP in the operating theatre, which on average occurs later (approximately within the last 30 minutes before skin incision). We test the hypothesis that strategy A is more effective in preventing SSI than strategy B. We will include a total of 5000 patients in abdominal, vascular and trauma surgery (2500 at each study site and 2500 per study group). All patients will be followed in the hospital for SSI occurrence. Additionally, all patients will be interviewed by telephone after hospital discharge at a defined follow-up period of 30 days (1 year if an implant is in place, such as hip endoprosthesis or meshes). We expect this study to be completed within approximately 3 years.

Conditions

Surgical Site Infection

Outcome Measures

Primary Outcomes (1)

• Surgical Site Infection (SSI)

  Surgical Site Infection within 30 days after index surgery

  30 days

Secondary Outcomes (6)

• All-cause 30 day mortality

  30 days

• Length of hospital stay

  1 year

• Economic burden of SSI

  1 year

• Nosocomial infections

  1 year

• In-hospital complications

  1 year

Study Arms (2)

Early Prophylaxis

EXPERIMENTAL

Early administration of SAP (Cefuroxime (plus metronidazole in colorectal surgery)) in anesthetic room (75 to 30 minutes prior to skin incision)

Procedure: Early administration of SAP (Cefuroxime (plus metronidazole in colorectal surgery)) in anesthetic room (75 to 30 minutes prior to skin incision)

Late Prophylaxis

ACTIVE COMPARATOR

Late administration of SAP (Cefuroxime (plus metronidazole in colorectal surgery)) in the operating theatre (within 30 minutes prior to skin incision)

Procedure: Late administration of SAP (Cefuroxime (plus metronidazole in colorectal surgery)) in the operating theatre (within 30 minutes prior to skin incision)

Interventions

Early administration of SAP (Cefuroxime (plus metronidazole in colorectal surgery)) in anesthetic room (75 to 30 minutes prior to skin incision) PROCEDURE

Early Prophylaxis

Late administration of SAP (Cefuroxime (plus metronidazole in colorectal surgery)) in the operating theatre (within 30 minutes prior to skin incision) PROCEDURE

Late Prophylaxis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Inpatient visceral, vascular and trauma procedures
• SAP indicated according to clinical standards (CDC guidelines for surgical wound classification)
• informed consent

You may not qualify if:

• Contraindication for study drugs
• Pre-existing antibiotic therapy within 14 days of surgery
• Any doubt that patients can make the decision to participate fully informed due to cognitive impairment, such as in critically ill or demented patients.
• Emergency procedures with planned incision within 2 hours after the surgeon indicated the procedure
• Participation in other studies that could potentially interfere with the present one (according to the ethics committee)
• Combined surgery including surgical subspecialties other than the above mentioned

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Cantonal Hospital of Aarau, Switzerland: collaborator

Study Sites (1)

University Hospital Basel

Basel, Canton of Basel-City, 4031, Switzerland

Location

Related Publications (4)

• Cristino MA, Nakano LC, Vasconcelos V, Correia RM, Flumignan RL. Prevention of infection in aortic or aortoiliac peripheral arterial reconstruction. Cochrane Database Syst Rev. 2025 Apr 22;4(4):CD015192. doi: 10.1002/14651858.CD015192.pub2.

  PMID: 40260835 DERIVED

• Kopp Lugli A, Marti WR, Salm L, Mujagic E, Bundi M, von Strauss M, Bucheli Laffer E, Landin J, Fux CA, Coslovsky M, Weber WP, Kindler C. The Role of HbA1c as a Positive Perioperative Predictor of Surgical Site and Other Postoperative Infections: An Explorative Analysis in Patients Undergoing Minor to Major Surgery. World J Surg. 2022 Feb;46(2):391-399. doi: 10.1007/s00268-021-06368-x. Epub 2021 Nov 8.

  PMID: 34750659 DERIVED

• Weber WP, Mujagic E, Zwahlen M, Bundi M, Hoffmann H, Soysal SD, Kraljevic M, Delko T, von Strauss M, Iselin L, Da Silva RXS, Zeindler J, Rosenthal R, Misteli H, Kindler C, Muller P, Saccilotto R, Lugli AK, Kaufmann M, Gurke L, von Holzen U, Oertli D, Bucheli-Laffer E, Landin J, Widmer AF, Fux CA, Marti WR. Timing of surgical antimicrobial prophylaxis: a phase 3 randomised controlled trial. Lancet Infect Dis. 2017 Jun;17(6):605-614. doi: 10.1016/S1473-3099(17)30176-7. Epub 2017 Apr 3.

  PMID: 28385346 DERIVED

• Mujagic E, Zwimpfer T, Marti WR, Zwahlen M, Hoffmann H, Kindler C, Fux C, Misteli H, Iselin L, Lugli AK, Nebiker CA, von Holzen U, Vinzens F, von Strauss M, Reck S, Kraljevic M, Widmer AF, Oertli D, Rosenthal R, Weber WP. Evaluating the optimal timing of surgical antimicrobial prophylaxis: study protocol for a randomized controlled trial. Trials. 2014 May 24;15:188. doi: 10.1186/1745-6215-15-188.

  PMID: 24885132 DERIVED

MeSH Terms

Conditions

Surgical Wound Infection

Interventions

Cefuroxime

Condition Hierarchy (Ancestors)

Wound Infection; Infections; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Walter P. Weber, MD

  University Hospital Basel, Basel 4031 Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2013
• First Posted: February 13, 2013
• Study Start: February 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: September 1, 2016
• Last Updated: September 29, 2016

Record last verified: 2016-09

Locations

CH (1)