Accelerated Flap Coverage in Severe Lower Extremity Trauma

NCT ID: NCT06293469

Last Updated: 2025-10-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 356 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-04
• Study Completion Date: 2030-02-28

Brief Summary

The goal of this randomized controlled trial is to determine if accelerated flap coverage compared to standard flap coverage timing leads to improved infection-related complications in patients with open fractures and/or dislocations below the knee. Eligible patients will be randomized to receive either a flap within a goal of 72 hours of injury or standard of care flap timing for the institution. The primary outcome will be a composite outcome to evaluate clinical status 6 months after randomization. Components of the composite outcome will be hierarchically assessed in the following order: 1) all-cause mortality, 2) amputation related to injury, 3) re-operation for infection and/or flap complication (flap compromise, partial and/or complete flap failure), and 4) days in hospital, defined as days in an acute in-patient hospital (i.e., not rehab or nursing facility).

Detailed Description

Infection following severe lower extremity musculoskeletal injuries is a challenging problem. Several factors hypothesized to influence infection have been explored and, in many cases, optimized or found not to be influential. A persistent area of uncertainty and variability is the timing of acute soft tissue coverage. In the United States, the mean time to coverage from injury is 10 days, and infection rates are 20-35%. In the United Kingdom, there are national guidelines to support coverage within 72 hours of injury, and infection rates are less than 10%. While the data to support early coverage is promising, the necessary evidence to make this significant change is lacking. To justify the mobilization of resources and expense required to shift practice, a definitive trial is needed. This trial seeks to fill this critical knowledge gap.

The primary objective of this trial is to determine if accelerated flap coverage (within 72 hours of injury) compared to standard flap coverage timing leads lower rates of infection and infection-related complications. The trial population includes patients 18 years and older with an acute open fracture and/or dislocation below the knee, with a diagnosed need for acute soft tissue coverage with a flap. Patients who undergo primary amputation prior to attempted flap coverage will be excluded. There will be 356 participants randomized in 1:1 ratio to receive either accelerated flap coverage (goal of flap within 72 hours from injury) or flap coverage at the time that reflects the standard of care at each institution. The timing of the trial interventions, other adjunctive treatments, the fracture fixation, and flap coverage procedures will be documented for both treatment groups. Management of the fracture or dislocation, selection of flap, and post-injury flap management will be at the discretion of the operating surgeons and documented for both treatment groups. Participants will have follow-up at 6 weeks, 3 months, 6 months, and 12 months post-randomization.

The primary outcome will be a composite outcome to evaluate clinical status 6 months after randomization. Components of the composite outcome will be hierarchically assessed in the following order: 1) all-cause mortality, 2) amputation related to injury, 3) re-operation for infection and/or flap complication (flap compromise, partial and/or complete flap failure), and 4) days in hospital, defined as days in an acute in-patient hospital (i.e., not rehab or nursing facility). The secondary outcomes will independently assess the individual components of the primary outcome at 6 and 12 months, the composite outcome at 12 months, and health-related quality of life and patient satisfaction over 6 and 12 months. An Adjudication Committee will review primary and secondary endpoints and a Data Safety Monitoring Committee (DSMC) will review all safety events.

Conditions

Open Tibia Fracture; Open Dislocation of Ankle; Extremity Fracture Lower; Extremity Injuries Lower

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Accelerated Flap Coverage

Accelerated flap surgery timing at a goal of within 72 hours from injury. Management of the fracture or dislocation, selection of flap, and post-injury flap management will be at the discretion of the operating surgeons and documented for both treatment groups.

Group Type: EXPERIMENTAL

Accelerated Flap Coverage Surgery

Intervention Type: PROCEDURE

Timing of the flap surgery is with a goal of 72 hours from injury

Standard of Care Flap Timing

The flap surgery will be performed at the standard of care timing for the institution. Management of the fracture or dislocation, selection of flap, and post-injury flap management will be at the discretion of the operating surgeons and documented for both treatment groups.

Group Type: ACTIVE_COMPARATOR

Standard of Care Flap Timing

Intervention Type: PROCEDURE

Timing of the flap surgery is the standard of care flap timing for the participating institution.

Interventions

Accelerated Flap Coverage Surgery

Timing of the flap surgery is with a goal of 72 hours from injury

Intervention Type: PROCEDURE

Standard of Care Flap Timing

Timing of the flap surgery is the standard of care flap timing for the participating institution.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. Patients 18 years of age or older.

2. Severe lower extremity open fracture and/or dislocation below the knee requiring an acute flap for management of the musculoskeletal injury.

3. Will have all planned flap surgeries performed by a participating surgeon or delegate.

4. Able to be randomized within 48 hours of injury.

Exclusion Criteria

1. Site is unable to implement the accelerated flap protocol due to local logistics.

2. Primary amputation anticipated prior to attempted flap for management of the injury.

3. Critical limb ischemia that requires re-vascularization for limb perfusion.

4. Chronic or acute infection at or near the musculoskeletal injury site at the time of initial injury surgery.

5. Burns at the musculoskeletal injury site.

6. Incarceration.

7. Expected injury survival of less than 12 months.

8. Terminal illness with expected survival of less than 12 months.

9. Currently enrolled in a trial that does not permit co-enrollment.

10. Declined to provide informed consent.

11. Unable to obtain informed consent due to language barriers.

12. Unable to obtain informed consent because a legally authorized representative was unavailable.

13. Anticipated problems, in the judgment of research personnel, with maintaining follow-up with the patient.

14. Prior enrollment in the trial.

15. Eligible patient or LAR was not approached within screening window (missed participant).

16. Other reason to exclude the patient, as approved by the Principal Investigators.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

McMaster University

OTHER

Sponsor Role: collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role: collaborator

Orthopaedic Trauma Association

OTHER

Sponsor Role: collaborator

Foundation of Orthopedic Trauma

OTHER

Sponsor Role: collaborator

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lily Mundy, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins School of Medicine

Locations

UC Davis Medical Center

Sacramento, California, United States

Site Status: RECRUITING

R Adams Cowley Shock Trauma Center

Baltimore, Maryland, United States

Site Status: RECRUITING

John Hopkins Bayview Medical Center

Baltimore, Maryland, United States

Site Status: RECRUITING

The Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status: RECRUITING

University of Maryland Capital Region Medical Center

Largo, Maryland, United States

Site Status: RECRUITING

Oregon Health & Science University

Portland, Oregon, United States

Site Status: RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status: RECRUITING

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status: RECRUITING

Vall d'Hebron University Hospital

Barcelona, , Spain

Site Status: RECRUITING

Countries

United States; Australia; Spain

Central Contacts

Lily Mundy, MD

Role: CONTACT

LMundy3@jhu.edu

410-706-2492

Facility Contacts

Ara A Salibian, MD

Role: primary

Mark J Gage, MD

Role: primary

Lily R Mundy, MD

Role: primary

Lily R Mundy, MD

Role: primary

Todd Jaeblon, MD

Role: primary

Graham J DeKeyser, MD

Role: primary

Lauren M Tatman, MD

Role: primary

Lipi Shukla, MBBS, PhD

Role: primary

Jordi Tomás-Hernández, MD

Role: primary

Other Identifiers

IRB00434587

Identifier Type: -

Identifier Source: org_study_id