Next Generation Sequencing (NGS)Phase 3NGSNCT07458230
Efficacy of Integrating Next Generation Sequencing for Treatment of Surgical Site Infection After Fracture Fixation:
A Phase 3 study testing NGS diagnostic findings in people with Next Generation Sequencing (NGS) and Surgical Site Infection (SSI), run by Johns Hopkins Bloomberg School of Public Health at 18 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 84 years
- Conditions the study is for
- Next Generation Sequencing (NGS), Surgical Site Infection (SSI), Fracture Fixation
- What is being tested?
- NGS diagnostic findings
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 18 sitesUnited States
- Study dates
- 1 Jan 2027to 1 Oct 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 84 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
18 sites in 1 country. Contact the study team or a site near you to ask about taking part.
18 sites in 1 country
United States18 sites
R Adams Cowley Shock Trauma Center
Baltimore, Maryland, 21201
Robert O'Toole, MD
Carolinas Medical Center
Charlotte, North Carolina, 28203
Madhav Karunakar, MD
UVA Health University Medical Center
Charlottesville, Virginia, 22908
David Weiss, MD
Ohio State University Hospital
Columbus, Ohio, 43210
Angela Collins, MD
Inova Fairfax Medical Campus
Fairfax, Virginia, 22042
Greg Gaski, MD
McGovern Medical School at UTHealth Houston
Houston, Texas, 77030
Stephen Warner, MD
Methodist Hospital
Indianapolis, Indiana, 46202
Roman Natoli, MD, 317-944-9400, rnatoli@IUhealth.org
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Patrick Bergin, MD
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03766
Leah Gitajn, MD
University of Southern California
Los Angeles, California, 90007
Joseph Patterson, MD
UW Health University Hospital
Madison, Wisconsin, 53792
Paul Whiting, MD
Loyola University Medical Center
Maywood, Illinois, 60153
Ashley Levack, MD
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
William Obremskey, MD
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Samir Mehta, MD
Warren Alpert Medical School of Brown University
Providence, Rhode Island, 02903
Andy Evans, MD
University of Utah Hospital
Salt Lake City, Utah, 84132
Thomas Higgins, MD
UCSF Medical Center
San Francisco, California, 94143
Saam Morshed, MD
University of Alabama
Tuscaloosa, Alabama, 35487
Clay Spitler, MD
About this study
Official title: 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.
Read more
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.
- Being tested
- NGS diagnostic findings
- Keywords
- Next Generation Sequencing (NGS)
- Medical subject headings
- Surgical Wound Infection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NGS diagnostic findingsDiagnostic test
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: NGS diagnostic findings |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2026
- Study start1 Jan 2027 (estimated)
- Primary completion1 Oct 2028 (estimated)
- Study completion1 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Next Generation Sequencing (NGS)Studies of the same condition, open and under way.
- More trials run by Johns Hopkins Bloomberg School of Public HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins Bloomberg School of Public Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Roman M Natoli, MD, Principal investigator, Indiana University, Methodist Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07458230
- Sponsor's protocol ID
- IRB00527101
- Other IDs
- HT9425-25-1-0210
- Acronym
- NGS
- Status last verified
- Nov 2026
- First submitted
- 3 Mar 2026
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Integrating Next Generation Sequencing for Treatment of Surgical Site Infection After Fracture Fixation: A Multicenter Randomized Control Trial
- ClinicalTrials.gov ID
- NCT07458230
- Acronym / sponsor ID
- NGS / IRB00527101
- Keywords
- Next Generation Sequencing (NGS)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Johns Hopkins Bloomberg School of Public HealthUniversity, hospital or other
- Study start
- 1 Jan 2027 (estimated)
- Primary completion
- 1 Oct 2028 (estimated)
- Study completion
- 1 Oct 2028 (estimated)
- First posted
- 9 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 | Diagnostic Test: NGS diagnostic findingsPatient 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. |
Who may qualify
- Ages
- 18 to 84 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NGS diagnostic findingsPatient 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 | Diagnostic Test: NGS diagnostic findings |
Primary outcome
Infection treatment failure rate
Time frame: 12 month
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Roman M Natoli, MD principal investigator
Indiana University, Methodist Hospital
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing NGS diagnostic findings in people with Next Generation Sequencing (NGS) and Surgical Site Infection (SSI), run by Johns Hopkins Bloomberg School of Public Health at 18 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Research Project Director (317-944-9400, schung60@jhu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Infection treatment failure rate (time frame: 12 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.