Acute Application of Antibiotic Powder in Open Fracture Wounds (APOW)

• ClinicalTrials.gov Identifier: NCT04872400
• Recruitment Status: Recruiting
• First Posted: May 4, 2021
• Last Update Posted: August 19, 2021
• Sponsor: University of Colorado, Denver
• Collaborator: Denver Health and Hospital Authority
• Information provided by (Responsible Party): University of Colorado, Denver

Study Description

Brief Summary:

The purpose of this study is to help determine the best treatment for severe injures like open fracture wounds.

Some broken bone injuries can be more likely to get an infection. It is mostly due to the way they were injured. Surgical site infection in the orthopedic surgery population is a big public health issue. Wound infections result in both longer length of hospital stay and total cost of care. This study will be using an antibiotic called Vancomycin or Tobramycin in a powder form.

Condition or disease	Intervention/treatment	Phase
Fractures, Open; Wounds and Injuries--Infections; Anti-Bacterial Agents; Fractures, Bone; Extremity Fracture Lower; Extremity Fractures Upper	Drug: Vancomycin; Drug: Tobramycin	Phase 4

Detailed Description:

The investigators aim to investigate the effectiveness of preoperative intrawound antibiotic powder in preventing infection and reducing bacterial burden after open fracture.

The investigators hypothesize that the participants who receive preoperative intrawound antibiotic powder will have fewer superficial and deep surgical site infections compared to participants who do not receive the antibiotic powder. The investigators also anticipate that the application of the antibiotic powder to open fracture wounds preoperatively will decrease the bacterial burden.

Sample swabs will be analyzed using the 16S metagenomics sequencing on the Illumina platform. Both RNA and DNA extracts will be utilized to identify and quantify the bacterial load in the wound bed at the time immediately prior to surgical debridement.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: The management of open fractures involves an expedited administration of systemic antibiotics and while effective in reducing the rate of infection, complications from infections are still common following open fractures. This trial aims to evaluate the incidence of surgical site infections using topical vancomycin antibiotic powder or topical tobramycin antibiotic powder in combination with standard of care treatment and to evaluate the effectiveness of both topical antibiotic powders in reducing surgical site infection.
• Masking: Single (Participant)
• Masking Description: This will be a single-blind study as only the participants will be blinded to the treatment.
• Primary Purpose: Prevention
• Official Title: Acute Application Of Intrawound Antibiotic Powder In Open Extremity Fracture Wounds
• Actual Study Start Date: June 14, 2021
• Estimated Primary Completion Date: December 31, 2022
• Estimated Study Completion Date: June 30, 2023

Arms and Interventions

Arm	Intervention/treatment
No Intervention: Control; Subjects randomized to the Control Arm will receive standard of care open fracture wound care (no powder) by the clinical team.
Experimental: Vancomycin; Subjects randomized to the Intervention arm will receive standard of care plus 1 gram of vancomycin powder applied topically to the wound bed before the dressing is applied. Intervention will occur in the emergency room prior to surgical intervention.	Drug: Vancomycin; 1 vial of Vancomycin 1g powder applied topically to the open fracture wound injury.
Experimental: Tobramycin; Subjects randomized to the Intervention arm will receive standard of care plus 1.2 grams of tobramycin powder applied topically to the wound bed before the dressing is applied. Intervention will occur in the emergency room prior to surgical intervention.	Drug: Tobramycin; 1 vial of Tobramycin 1.2g powder applied topically to the open fracture wound injury.

Outcome Measures

Primary Outcome Measures :

1. Incidence of surgical site infection during the post-operative follow-up period [ Time Frame: Within 6 months of injury date ]
   The percentage of participants who develop an infection at the surgical site following debridement and fixation at the follow up period.

Secondary Outcome Measures :

1. Shannon's index measure of bacterial diversity based on wound cultures [ Time Frame: Within 1 year of injury date ]
   Characterize species and determine whether changes in biodiversity differ across study arms.
2. Simpson index measure of bacterial diversity based on the wound cultures [ Time Frame: Within 1 year of injury date ]
   Consider the number of bacterial species present, alongside the relative abundance of each specie across study arms.
3. Presence of bacterial species commonly attributed to surgical site infections based on would cultures including: Staph, enterococcus, acinetobacter, enterobacter, e. coli, klebsiella, and pseudomonas [ Time Frame: Within 1 year of injury date ]
   Understand the changes that occur in the presence of bacterial species associated with surgical site infection after antibiotic powder treatment .

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Subject or proxy willing and able to provide written informed consent.
• Age between 18 years and 80 years (inclusive), with an upper or lower extremity Gustilo Type II, IIIA, or IIIB open fractures requiring debridement and internal fixation.
• Open extremity fractures
• Time from injury to study intervention 24 hours or less

Exclusion Criteria:

• Individuals under the age of 18 years or over 80 years
• Type I or IIIC open fractures
• Over 24 hours from time of injury
• Subjects who have received acute operative care of the open fracture at an outside facility prior to presenting at the Emergency Department.
• Open fractures distal to the wrist and midfoot
• History of chronic infection in the extremity involved.
• Subjects who are currently pregnant
• Subjects who are Prisoners
• Subjects with a known allergy to vancomycin or tobramycin
• Subjects with a condition or social circumstances that would reduce adherence and follow-up.
• Subjects Participating in other clinical research involving investigational antimicrobial products within 30 days of randomization.

Contacts and Locations

Contacts

Contact: Nicholas Alfonso, MD; 303-724-5860; nicholas.alfonso@cuanschutz.edu

Locations

United States, Colorado

University of Colorado Anschutz; Recruiting

Aurora, Colorado, United States, 80045

Contact: Nicholas Alfonso, MD 303-724-5860 nicholas.alfonso@cuanschutz.edu

Contact: Eseosa Enabulele, BDS, MPH 303-724-4231 eseosa.enabulele@cuanschutz.edu

Denver Health and Hospital Authority; Not yet recruiting

Denver, Colorado, United States, 80204

Contact: Cyril Mauffrey, MD 303-436-4949 cyril.mauffrey@dhha.org

Sponsors and Collaborators

University of Colorado, Denver

Denver Health and Hospital Authority

Investigators

• Principal Investigator: Nicholas Alfonso, MD; University of Colorado, Denver

More Information

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT04872400
• Other Study ID Numbers: 20-2957; 5672 ( Other Grant/Funding Number: Orthopaedic Trauma Association )
• First Posted: May 4, 2021
• Last Update Posted: August 19, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Colorado, Denver:

Open fractures; Antibiotic powder; Vancomycin; Tobramycin; Infection; Gustilo; 16S

Additional relevant MeSH terms:

Fractures, Bone; Wounds and Injuries; Fractures, Open; Vancomycin; Tobramycin; Anti-Bacterial Agents; Anti-Infective Agents