NCT07458230

Brief Summary

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.

Trial Health

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Trial Health Score

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Enrollment
250

participants targeted

Target at P50-P75 for phase_3

Timeline
27mo left

Started Jul 2026

Geographic Reach
1 country

18 active sites

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 3, 2026

Completed
6 days until next milestone

First Posted

Study publicly available on registry

March 9, 2026

Completed
4 months until next milestone

Study Start

First participant enrolled

July 1, 2026

Expected
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2028

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2028

Last Updated

May 8, 2026

Status Verified

May 1, 2026

Enrollment Period

2.3 years

First QC Date

March 3, 2026

Last Update Submit

May 7, 2026

Conditions

Keywords

Next Generation Sequencing (NGS)

Outcome Measures

Primary Outcomes (1)

  • 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

Study Arms (2)

Standard of Care (Control)

NO INTERVENTION

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.

Diagnostic Test: NGS diagnostic findings

EXPERIMENTAL

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

Interventions

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.

Diagnostic Test: NGS diagnostic findings

Eligibility Criteria

Age18 Years - 84 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (18)

University of Alabama

Tuscaloosa, Alabama, 35487, United States

Location

University of Southern California

Los Angeles, California, 90007, United States

Location

UCSF Medical Center

San Francisco, California, 94143, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

R Adams Cowley Shock Trauma Center

Baltimore, Maryland, 21201, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03766, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

Location

Ohio State University Hospital

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Warren Alpert Medical School of Brown University

Providence, Rhode Island, 02903, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

McGovern Medical School at UTHealth Houston

Houston, Texas, 77030, United States

Location

University of Utah Hospital

Salt Lake City, Utah, 84132, United States

Location

UVA Health University Medical Center

Charlottesville, Virginia, 22908, United States

Location

Inova Fairfax Medical Campus

Fairfax, Virginia, 22042, United States

Location

UW Health University Hospital

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Surgical Wound Infection

Condition Hierarchy (Ancestors)

Wound InfectionInfectionsPostoperative ComplicationsPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Roman M Natoli, MD

    Indiana University, Methodist Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Research Project Director

CONTACT

Clinical Research Manager

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, CARE PROVIDER
Masking Details
NGS results withheld from care team in one arm
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 3, 2026

First Posted

March 9, 2026

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

October 1, 2028

Study Completion (Estimated)

October 1, 2028

Last Updated

May 8, 2026

Record last verified: 2026-05

Locations