Wound Infections Following Implant Removal (WIFI)

Antibiotic Prophylaxis to Prevent Wound Infections Following Implant Removal

In the Netherlands about 18,000 surgical procedures with implant removal are annually performed after fracture healing, of which 30-80% concern the foot, ankle and lower leg region. For clean surgical procedures, the rate of postoperative wound infections (POWIs) should be less than 5%. However, rates of 10-12% following implant removal, specifically after foot, ankle and lower leg fractures are reported. Currently, surgeons decide individually if antibiotics prophylaxis is given, since no guideline exists. This leads to undesirable practice variation.

Therefore, the investigators propose a double-blind randomized controlled trial (RCT) in patients scheduled for implant removal following a foot, ankle or lower leg fracture, to assess the (cost-)effectiveness of a single gift of antibiotic prophylaxis. Primary outcome is a POWI within 30 days after implant removal. Secondary outcomes are quality of life, functional outcome at 30 days and 6 months after implant removal and costs.

With 2 x 250 patients a decrease in POWI from 10% to 3.3% (expected rate in clean-contaminated elective orthopedic trauma procedures) can be detected (Power=80%, 2-sided alpha=5%, including 15% lost to follow up).

If the assumption of the investigators, that prophylactic antibiotics prior to implant removal reduces the infectious complication rate, is confirmed by this RCT, this will offer a strong argument to adopt a single gift of antibiotic prophylaxis as standard practice of care. This will reduce the incidence of POWIs and consequently will lead to less physical and social disabilities and health care use. In addition, it will decrease the rate of use of empiric broad-spectrum antibiotics (and antibiotic resistance) prescribed upon suspicion or diagnosis of a POWI. A preliminary, conservative estimation suggests yearly cost savings in the Netherlands of €3.5 million per year.

Study Overview

• Status: Completed
• Conditions: Surgical Wound Infection
• Intervention / Treatment: Drug: Cephalozin; Other: Sodium chloride

Detailed Description

See study protocol

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Alkmaar, Netherlands
    • Medisch Centrum Alkmaar
  • Almere, Netherlands
    • Flevoziekenhuis
  • Amstelveen, Netherlands
    • Amstelland Ziekenhuis
  • Amsterdam, Netherlands
    • VU Medisch Centrum
  • Amsterdam, Netherlands
    • Onze Lieve Vrouwe Gasthuis
  • Amsterdam, Netherlands
    • Academic Medical Center
  • Amsterdam, Netherlands
    • BovenIJ Ziekenhuis
  • Amsterdam, Netherlands
    • Sint Lucas Andreas Ziekenhuis
  • Apeldoorn, Netherlands
    • Gelre Ziekenhuizen
  • Beverwijk, Netherlands
    • Rode Kruis Ziekenhuis
  • Breda, Netherlands
    • Amphia ziekenhuis
  • Delft, Netherlands
    • Reinier de Graaf
  • Den Haag, Netherlands
    • MC Haaglanden
  • Deventer, Netherlands
    • Deventer Ziekenhuis
  • Eindhoven, Netherlands
    • Catharina Ziekenhuis
  • Helmond, Netherlands
    • Elkerliek Ziekenhuis
  • Hilversum, Netherlands
    • Tergooiziekenhuizen
  • Hoofddorp, Netherlands
    • Spaarne Ziekenhuis
  • Hoorn, Netherlands
    • Westfries Gasthuis
  • Leiderdorp, Netherlands
    • Rijnland Ziekenhuis
  • Schiedam, Netherlands
    • Vlietland ziekenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients ≥18 years and ≤75 years of all ethnic backgrounds
• Implant removal following foot, ankle and/or lower leg surgery

Exclusion Criteria:

• Removing and re-implanting osteosynthesis material in the same session
• Active wound infection or (plate) fistula
• Antibiotic treatment at time of elective implant removal for a concomitant disease or infection
• A medical history of an allergic reaction to a cephalosporin, penicillin, or any other β-lactam antibiotic.
• Insufficient comprehension of the Dutch language to understand the patient information to make an informed decision to participate.
• Kidney disease (eGFR <60 ml/min/1.73m^2).
• Treatment with probenecide, anticoagulants (see SPC)
• Pregnancy and lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: antibiotic prophylaxis; a single gift of 1000 mg cefazolin in 10 cc of NaCl 0.9% (intervention group)	Drug: Cephalozin; 1000 mg Cephalozin; Other Names: Kefzol
Placebo Comparator: No antibiotic prophylaxis; a single gift of 10 cc NaCl 0.9%, given in the same manner (control group).	Other: Sodium chloride; 10 cc of NaCl 0.9%; Other Names: NaCl 0.9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative wound infection (POWI)	The primary outcome variable is a POWI within 30 days after implant removal as defined by the criteria applied by the Centers for Disease and Control.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-related quality of life	Health-related quality of life (as measured by the EQ-5D questionnaire)	baseline, one month, 6 months
Functional outcome	Functional outcome following implant removal as assessed with the Lower Extremity Functional Scale (LEFS). The LEFS can be used by clinicians as a measure of patients' initial function, ongoing progress and outcome, as well as to set functional goals. The LEFS can be used to evaluate the functional impairment of a patient with a disorder of one or both lower extremities. It can be used to monitor the patient over time and to evaluate the effectiveness of an intervention	baseline, 1 month, 6 months
Patient satisfaction	Patient satisfaction following implant removal as measured by a ten-point Visual Analog Scale	1 month, 6 months
Health care resources utilization	Health care resources utilization at baseline, 1 month and 6 months after implant removal (including amongst others, number of visits to the general practitioner and use of home care organizations) as measured by way of a combination of the Dutch iMTA Medical Consumption Questionnaire (iMCQ) and iMTA Productivity Cost Questionnaire (iPCQ) (adapted to the study setting).	baseline, 1 month, 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Costs	Costs (economic evaluation including budget impact analysis): the economic evaluation of antibiotic prophylaxis in patients scheduled for implant removal (following a foot, ankle or lower leg fracture) against no prophylaxis as its best alternative will be performed as a cost-effectiveness (CEA) as well as a cost-utility (CUA) analysis.	Costs per quality adjusted life year

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development; AO Research Fund
• Investigators: Study Chair: Manouk Backes, MD, MSc, Academic Medical Center/Sint Lucas Andreas Hospital; Study Director: Tim Schepers, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Publications and helpful links

General Publications

• Backes M, Schep NW, Luitse JS, Goslings JC, Schepers T. Indications for implant removal following intra-articular calcaneal fractures and subsequent complications. Foot Ankle Int. 2013 Nov;34(11):1521-5. doi: 10.1177/1071100713502466. Epub 2013 Sep 13.
• Backes M, Dingemans SA, Schep NW, Bloemers FW, Van Dijkman B, Garssen FP, Haverlag R, Hoogendoorn JM, Joosse P, Mirck B, Postma V, Ritchie E, Roerdink WH, Sintenie JB, Soesman NM, Sosef NL, Twigt BA, Van Veen RN, Van der Veen AH, Van Velde R, Vos DI, De Vries MR, Winkelhagen J, Goslings JC, Schepers T. Wound Infections Following Implant removal below the knee: the effect of antibiotic prophylaxis; the WIFI-trial, a multi-centre randomized controlled trial. BMC Surg. 2015 Feb 6;15:12. doi: 10.1186/1471-2482-15-12.
• Backes M, Dingemans SA, Dijkgraaf MGW, van den Berg HR, van Dijkman B, Hoogendoorn JM, Joosse P, Ritchie ED, Roerdink WH, Schots JPM, Sosef NL, Spijkerman IJB, Twigt BA, van der Veen AH, van Veen RN, Vermeulen J, Vos DI, Winkelhagen J, Goslings JC, Schepers T; WIFI Collaboration Group. Effect of Antibiotic Prophylaxis on Surgical Site Infections Following Removal of Orthopedic Implants Used for Treatment of Foot, Ankle, and Lower Leg Fractures: A Randomized Clinical Trial. JAMA. 2017 Dec 26;318(24):2438-2445. doi: 10.1001/jama.2017.19343. Erratum In: JAMA. 2018 Mar 13;319(10 ):1051.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: August 25, 2014
• First Submitted That Met QC Criteria: August 25, 2014
• First Posted (Estimate): August 26, 2014

Study Record Updates

• Last Update Posted (Estimate): December 22, 2016
• Last Update Submitted That Met QC Criteria: December 21, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Orthopedics; Postoperative wound infection; Antibiotic Prophylaxis; Implant Removal
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Disease Attributes; Infections; Communicable Diseases; Wounds and Injuries; Surgical Wound; Surgical Wound Infection; Wound Infection
• Other Study ID Numbers: SB155014; NTR 4393 (Other Identifier: Nederlands Trial Register)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED