Powdered Intrawound Vancomycin in Open Fractures Trial (PIVOT)

Powdered Intrawound Vancomycin in Open Fractures: a Randomized Controlled Trial

The purpose of this randomized control trial is to compare the rate of post-operative infection in patients with open fractures in upper or lower extremity long bones randomized to receive intra-operative intrawound topical vancomycin powder on their open fractures in addition to the current best practice of intravenous antibiotics with irrigation and debridement compared to intravenous antibiotics with irrigation and debridement alone during definitive operative fixation of the fracture.

Study Overview

• Status: Not yet recruiting
• Conditions: Fractures, Bone; Trauma; Wound Infection; Fractures, Open; Infection, Surgical Site; Open Fracture; Post-Operative Wound Infection
• Intervention / Treatment: Drug: Vancomycin 1000 MG

Detailed Description

Primary Objective:

To evaluate the effect of intra-operative intrawound topical vancomycin powder on open fractures in addition to the current best practice of intravenous antibiotics with irrigation and debridement compared to intravenous antibiotics with irrigation and debridement alone during definitive fixation of the fracture on deep surgical site infection, defined as a post-operative surgical infection requiring return to the operating room for irrigation and debridement with or without hardware removal/revision within the first six months following surgery.

Secondary Objectives:

To evaluate the effect of intra-operative intrawound topical vancomycin powder on superficial surgical site infection, defined as a post-operative infection that required antibiotic treatment but no return to the operating room, readmissions to hospital for post-operative surgical infection (deep or superficial), and hardware failure, defined as hardware loosening, loss of fixation, hardware fracture, or hardware migration, visualized either on imaging or found intra-operatively.

To evaluate differences in microbe characteristics in cultures taken intra-operatively in the take-back irrigation and debridement surgery in patients with deep surgical site infection.

To evaluate if the effect of intra-operative intrawound topical vancomycin powder changes based on fracture and patient characteristics: upper extremity versus lower extremity, Gustilo Classification, patients with documented Methicillin-resistant Staphylococcus aureus (MRSA) colonization, and mechanism of injury.

To evaluate if certain fracture and patient characteristics: upper extremity versus lower extremity, Gustilo Classification, patients with documented Methicillin-resistant Staphylococcus aureus (MRSA) colonization, and by their mechanism of injury increases the risk of infection in both the treatment and control group.

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Gabriel Larose, MD, MSc, FRCSC; Phone Number: 2047872261; Email: glarose@hsc.mb.ca
• Study Contact Backup: Name: Madison Price, MD; Email: pricem@myumanitoba.ca

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Health Sciences Centre Winnipeg

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 18 years or older at time of surgery
• Patients with an open fracture classified as Gustilo Type I to IIIc in the clavicle, humerus, radius, ulna, metacarpals, upper extremity phalanges (fingers), femur, tibia, fibula and metatarsals and lower extremity phalanges (toes).
• Open fracture treated operatively with plate(s) and screw(s) hardware fixation and intramedullary fixation (IM nail).
• Able to attend standard of care follow up for six months post-operatively

Exclusion Criteria:

• Patients with known vancomycin allergy, drug administration reaction, or other sensitivities to vancomycin.
• Patients who have already had definitive fracture fixation before enrollment in the study
• Patients with open fracture already infected at time of enrollment
• Patients with current positive blood cultures (bacteremia) at time of enrollment (current, meaning they have not received treatment and now have negative most-recent blood cultures).
• Patients who have other forms of local antibiotics that are left in place at the end of the definitive fixation surgery (e.g., antibiotic loaded cement or polymethyl methacrylate (PMMA) beads)
• Patients who do not speak English
• Patients who are currently pregnant
• Patients who are unable to provide consent and do not have a substitute decision maker able to provide consent
• Patients who will have severe difficulty with follow up

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Powdered, intrawound vancomycin 1000 mg at the time of definitive surgery for open fracture fixation in addition to the current best practice of intravenous antibiotics with irrigation and debridement	Drug: Vancomycin 1000 MG; Powdered, intrawound vancomycin 1000 mg at the time of definitive surgery for open fracture fixation in addition to the current best practice of intravenous antibiotics with irrigation and debridement; Other Names: Treatment
No Intervention: Control; Intravenous antibiotics with irrigation and debridement alone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Deep surgical site infection	A post-operative surgical infection requiring return to the operating room for irrigation and debridement with or without hardware removal/revision after the definitive fixation.	Within six months of definitive surgical orthopedic fixation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Superficial surgical site infection	A post-operative infection that required antibiotic treatment but no return to the operating room	Within six months of definitive surgical orthopedic fixation
Hardware failure visualized either on imaging or found intra-operatively, until six months post definitive fixation	Hardware loosening, loss of fixation, hardware fracture, or hardware migration visualized either on imaging or found intra-operatively	Up until six months following definitive fixation
Microbe sensitivity	In patients with deep surgical site infection, the gram stain and sensitivity and resistance to antibiotics of cultures taken intra-operatively in the take-back irrigation and debridement surgery	Up until six months following definitive fixation
Fracture location	Whether the fracture is in the upper extremity: clavicle, humerus, radius, ulna, metacarpals and phalanges (fingers) versus lower extremity: femur, tibia, fibula, metatarsals, and phalanges (toes).	At time of initial open fracture
Fracture Gustilo Classification	Open fracture classification from Type I to IIIc that classifies open fractures based on extent of bone, soft tissue and vascular injuries.	At time of definitive surgical orthopedic fixation.
Mechanism of injury	Mechanism of injury will be categorized as: i. Motor vehicle collision: car occupant, pedestrian, motorcyclist, other ii. Other Vehicle Accident: all-terrain vehicle (ATV), bicycle, snowmobile iii. Fall: from own height (slip/stumble), from height less than or equal to 3 metres, from height greater than 3 metres iv. Laceration v. Striking with blunt object (unintentional) vi. Crush injury vii. Sport related injury viii. Interpersonal violence: stabbing, striking with sharp object (e.g., machete), striking with blunt object, gunshot, other	At time of initial open fracture
MRSA colonization	Nasal swab for MRSA that is routinely taken for all patients admitted to the study's hospital	During initial admission to hospital for open fracture

Collaborators and Investigators

• Sponsor: University of Manitoba
• Collaborators: Health Sciences Centre, Winnipeg, Manitoba
• Investigators: Principal Investigator: Gabriel Larose, MD, MSc, FRCSC, University of Manitoba; Principal Investigator: Madison Price, MD, University of Manitoba

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: July 10, 2024
• First Submitted That Met QC Criteria: July 10, 2024
• First Posted (Actual): July 17, 2024

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 17, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: trauma; infection; vancomycin; open fracture; intrawound
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Disease Attributes; Infections; Communicable Diseases; Wounds and Injuries; Fractures, Bone; Surgical Wound; Surgical Wound Infection; Wound Infection; Fractures, Open; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin
• Other Study ID Numbers: HS26510 (B2024:071)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No