Efficacy of Integrating Next Generation Sequencing for Treatment of Surgical Site Infection After Fracture Fixation: (NGS)

Efficacy of Integrating Next Generation Sequencing for Treatment of Surgical Site Infection After Fracture Fixation: A Multicenter Randomized Control Trial

The study focuses on the serious problem of infections and wound-healing issues that can happen after high-energy bone fractures. These complications are common and can affect between 10% and 60% of patients, especially those with severe injuries. When a fracture is repaired with surgery and an infection develops afterward, patients often face long recovery times, more pain, and sometimes multiple surgeries. In the worst cases, the infection can lead to permanent disability or even amputation. The current standard test used in hospitals, called a culture, often misses certain bacteria, which can make treatment less effective. Because of this, the study aims to find out whether adding a newer test called Next Generation Sequencing (NGS) can help doctors identify infections more accurately and improve patient outcomes.

The main goal of the study is to see whether using NGS along with standard hospital cultures reduces the number of treatment failures compared to using standard cultures alone. Treatment failure means the infection does not get better and the patient must return to the operating room. The study also wants to learn whether NGS helps doctors make better antibiotic choices and avoid unnecessary or ineffective treatments. Another goal is to understand which NGS results are most helpful when doctors decide to change a patient's antibiotics. By learning this, researchers hope to create a model that explains how NGS information influences treatment decisions.

To join the study, patients must be between 18 and 84 years old and have a deep infection after a fracture was repaired with internal fixation, such as plates, screws, or rods. Patients must also meet infection criteria from either the Fracture-Related Infection (FRI) guidelines or the CDC's infection criteria. A total of 250 patients will be randomly placed into one of two groups: one group will receive treatment guided by both NGS and standard cultures, while the other group will receive treatment based only on standard cultures. Researchers will then compare how often treatment fails in each group.

Treatment failure includes several possible outcomes. The most important is an unplanned return to the operating room because the infection did not improve. Other types of failure include new superficial infections that do not require surgery, bones that fail to heal properly (called nonunion), amputation, and complications caused by antibiotics. Patients will return for follow-up visits at 2 weeks, 6 weeks, 3 months, 6 months, and 12 months after joining the study so researchers can track the patient's progress and monitor for any problems.

Right now, the failure rate for treating these infections using standard hospital cultures is about 30%, which is considered unacceptably high. The researchers believe that adding NGS will help lower this number because NGS can detect more types of bacteria, including ones that are hard to grow in a lab. With better information, doctors can choose antibiotics that are more likely to work the first time, which may reduce the need for additional surgeries and improve healing. This could be especially important for military service members, who often suffer high-energy injuries and face a greater risk of long-term complications if treatment fails.

NGS is already available, covered by Medicare, and fast enough to be useful in real-time medical decisions. If this study shows that NGS improves treatment outcomes, hospitals could begin using it widely and quickly. The researchers hope that this approach will lead to fewer infections, better antibiotic use, faster recovery, and improved long-term function for patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Next Generation Sequencing (NGS); Fracture Fixation; Surgical Site Infection (SSI)
• Intervention / Treatment: Diagnostic test: NGS diagnostic findings

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Research Project Director; Phone Number: 317-944-9400; Email: schung60@jhu.edu
• Study Contact Backup: Name: Clinical Research Manager; Phone Number: 317-944-9400; Email: acarlini@jhu.edu

Study Locations

• United States
  • Alabama
    • Tuscaloosa, Alabama, United States, 35487
      • University of Alabama
      • Contact: Clay Spitler, MD
  • California
    • Los Angeles, California, United States, 90007
      • University of Southern California
      • Contact: Joseph Patterson, MD
    • San Francisco, California, United States, 94143
      • UCSF Medical Center
      • Contact: Saam Morshed, MD
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
      • Contact: Ashley Levack, MD
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Methodist Hospital
      • Contact: Roman Natoli, MD; Phone Number: 317-944-9400; Email: rnatoli@IUhealth.org
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • R Adams Cowley Shock Trauma Center
      • Contact: Robert O'Toole, MD
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
      • Contact: Patrick Bergin, MD
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Dartmouth Hitchcock Medical Center
      • Contact: Leah Gitajn, MD
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center
      • Contact: Madhav Karunakar, MD
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Hospital
      • Contact: Angela Collins, MD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
      • Contact: Samir Mehta, MD
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Warren Alpert Medical School of Brown University
      • Contact: Andy Evans, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
      • Contact: William Obremskey, MD
  • Texas
    • Houston, Texas, United States, 77030
      • McGovern Medical School at UTHealth Houston
      • Contact: Stephen Warner, MD
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital
      • Contact: Thomas Higgins, MD
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • UVA Health University Medical Center
      • Contact: David Weiss, MD
    • Fairfax, Virginia, United States, 22042
      • Inova Fairfax Medical Campus
      • Contact: Greg Gaski, MD
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • UW Health University Hospital
      • Contact: Paul Whiting, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 18-84 years
• History of extremity fracture proximal to the metatarsals and carpal bones treated with any type of internal fixation. Note that both healed and unhealed fractures are eligible.
• Deep infection requiring surgery after fracture fixation as determined by either of the following:

FRI confirmatory criteria CDC criteria (without the timeframe). This includes the possibility of culture negative infection but determined to be infection by treatment team.

• Plan for treatment includes antibiotic therapy prescribed by Infectious Disease provider(s), regardless of SOCHB culture or NGS results.

Exclusion Criteria:

• Spine fractures
• High risk of amputation based on the initial managing physician opinion
• Incarcerated/institutionalized
• Patient is too sick to have surgery, i.e., medical co-morbidities which preclude treatment with a general anesthetic
• Prior history of chronic infection at the surgical site
• Pathological fractures from a neoplastic process
• History of Paget's Disease
• Unavailable for the planned 12 months of follow-up (e.g., planned follow-up at a location other than one of the study sites)
• Extremity fracture occurred more than 2 years prior to the hospital admission for the presenting infection

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
No Intervention: Standard of Care (Control); Participants in this group will receive standard of care treatment for FRI. The care team will Not be provided with NGS data. Treatment strategy will be entirely based on SOCHB culture assessment strategies.
Experimental: Diagnostic Test: NGS diagnostic findings; Patient will receive antibiotic treatment and course using the NGS results. The clinical care team will be provided with NGS diagnostic findings along with SOCHB culture data.	Diagnostic test: NGS diagnostic findings; Patient will receive antibiotic treatment and course using the NGS results. the investigators will require antibiotic treatment of any NGS finding that is not treated based on the results of SOCHB culture alone. Site PIs have agreed to integrate NGS results into the treatment plan. If the antibiotic plan contradicts the NGS-based results, alternative antibiotic selection and reason (e.g., allergy to an antibiotic, cost-prohibitive) will be documented in specific CRFs. All other treatments will be per SOC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infection treatment failure rate	Infection treatment failure rate, defined as unplanned return to the operating room for infection after randomization. Infection at this time will be similarly defined as in the inclusion criteria, namely FRI confirmatory criteria and/or, CDC criteria (without the timeframe). This includes the possibility of culture negative infection but determined to be infection by the treatment team.	12 month

Collaborators and Investigators

• Sponsor: Johns Hopkins Bloomberg School of Public Health
• Investigators: Principal Investigator: Roman M Natoli, MD, Indiana University, Methodist Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: March 3, 2026
• First Submitted That Met QC Criteria: March 3, 2026
• First Posted (Actual): March 9, 2026

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Next Generation Sequencing (NGS)
• Additional Relevant MeSH Terms: Postoperative Complications; Pathologic Processes; Infections; Wound Infection; Pathological Conditions, Signs and Symptoms; Surgical Wound Infection
• Other Study ID Numbers: IRB00527101; HT9425-25-1-0210 (Other Grant/Funding Number: DOD PRORP/CDMRP)

Drug and device information, study documents

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