Accelerated Flap Coverage Versus Standard Timing in the Treatment of Severe Lower Extremity Musculoskeletal Injuries (FLAP ATTACK)

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Open Tibia Fracture; Extremity Fracture Lower; Open Dislocation of Ankle; Extremity Injuries Lower
• Intervention / Treatment: Procedure: Accelerated Flap Coverage Surgery; Procedure: Standard of Care Flap Timing

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.

• Study Type: Interventional
• Enrollment (Estimated): 356
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lily Mundy, MD; Phone Number: (410)706-2492; Email: lmundy3@jhu.edu

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner - University Medical Center Phoenix
      • Contact: Michael McKee, MD; Phone Number: 602-839-2000; Email: michael.mckee@bannerhealth.com
  • California
    • Los Angeles, California, United States, 90033
      • Keck Hospital of USC
      • Contact: Joseph Patterson, MD; Phone Number: 800-872-2273; Email: Joseph.Patterson@med.usc.edu
    • Los Angeles, California, United States, 90033
      • Los Angeles Medical Center
      • Contact: Joseph Patterson, MD; Phone Number: 323-409-1000; Email: Joseph.Patterson@med.usc.edu
    • Los Angeles, California, United States, 90084
      • Cedars-Sinai Medical Center
      • Contact: Geoffrey Marecek, MD; Phone Number: 310-423-3277; Email: gmarecek@gmail.com
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
      • Contact: Ara Salibian, MD; Phone Number: 916-734-2011; Email: asalibian@ucdavis.edu
    • San Diego, California, United States, 92121
      • UC San Diego Health
      • Contact: Kathryn Dwight, MD; Phone Number: 858-657-8737; Email: kddwight@health.ucsd.edu
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale New Haven Hospital
      • Contact: David Colen, MD; Phone Number: 203-688-4242; Email: david.colen@yale.edu
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medicine
      • Contact: Maureen Beederman, MD; Phone Number: 888-824-0200; Email: mbeederman@bsd.uchicago.edu
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • IU Health University Hospital
      • Contact: Erin Weber, MD; Phone Number: 317-944-5000; Email: eweber4@iuhealth.org
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Health Sciences Center
      • Contact: Jessica Rivera, MD; Phone Number: 504-568-4808; Email: jrive5@lsuhsc.edu
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
      • Contact: Lily Mundy; Phone Number: 410-706-2492; Email: LMundy3@jhu.edu
    • Baltimore, Maryland, United States, 21201
      • University of Maryland - Shock Trauma Center
      • Contact: Mark Gage, MD; Phone Number: 410-448-6400; Email: MGage@som.umaryland.edu
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Hospital - Bayview Medical Center
      • Contact: Lily Mundy, MD; Phone Number: 410-550-0100; Email: lmundy3@jhu.edu
    • Largo, Maryland, United States, 20774
      • University of Maryland - Capital Region
      • Contact: Mark Gage, MD; Phone Number: 240-677-1000; Email: MGage@som.umaryland.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
      • Contact: Lydia Helliwell, MD; Phone Number: 617-732-5500; Email: LHELLIWELL@BWH.HARVARD.EDU
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
      • Contact: Patrick Bergin, MD; Phone Number: 601-984-1000; Email: PBergin@umc.edu
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri Hospital
      • Contact: Gregory Della Rocca; Phone Number: 573-882-4141; Email: dellaroccag@health.missouri.edu
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
      • Contact: Andrew Hollins, MD; Phone Number: 402-559-4000; Email: ahollins@unmc.edu
  • New York
    • The Bronx, New York, United States, 11418
      • Jamaica Hospital Medical Center
      • Contact: Abhishek Ganta, MD; Phone Number: 718-206-6000; Email: abhishek.ganta@nyulangone.org
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
      • Contact: Michael Beltran, MD; Phone Number: 513-584-1000; Email: beltrame@ucmail.uc.edu
    • Columbus, Ohio, United States, 43221
      • Ohio State University Wexner Medical Center
      • Contact: Angela Collins; Phone Number: 614-293-5084; Email: angela.collins@osumc.edu
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
      • Contact: Michael Johnson, MD; Phone Number: 937-208-8000; Email: michael.johnson@wright.edu
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
      • Contact: Graham DeKeyser, MD; Phone Number: 503-494-8311; Email: dekeyser@ohsu.edu
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Brown University Health
      • Contact: Franca Kraenzlin, MD; Phone Number: 401-444-3500; Email: FKraenzlin@brownhealth.org
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
      • Contact: Lauren Tatman, MD; Phone Number: 615-322-5000; Email: lauren.m.tatman@vumc.org
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston
      • Contact: Mohin Bhadkamkar, MD; Phone Number: 713-500-4472; Email: Mohin.Bhadkamkar@uth.tmc.edu
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital
      • Contact: Lucas Marchand, MD; Phone Number: 801-581-2121; Email: Lucas.Marchand@hsc.utah.edu
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • INOVA Fairfax Hospital
      • Contact: Abraham Goch, MD; Phone Number: 703-776-4001; Email: Abraham.goch@inova.org
  • Washington
    • Seattle, Washington, United States, 98195
      • UW Medical Center
      • Contact: Jeffrey Friedrich, MD; Phone Number: 206-598-3300; Email: jfriedri@uw.edu
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Health University Hospital
      • Contact: Christopher Domes, MD; Phone Number: 608-263-6400; Email: domes@ortho.wisc.edu
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
      • Contact: Elizabeth Harkin, MD; Phone Number: 414-955-8296; Email: elizabeth.harkin.md@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients 18 years of age or older.
• Severe lower extremity open fracture and/or dislocation below the knee requiring an acute flap for management of the musculoskeletal injury.
• Treating surgeon is willing to comply with treatment allocation.
• Able to be randomized within 72 hours of injury.

Exclusion Criteria:

• Site is unable to implement the accelerated flap protocol due to local logistics.
• Primary amputation anticipated prior to attempted flap for management of the injury.
• Critical limb ischemia that requires re-vascularization for limb perfusion.
• Chronic or acute infection at or near the musculoskeletal injury site at the time of initial injury surgery.
• Burns at the musculoskeletal injury site.
• Incarceration.
• Expected injury survival of less than 12 months.
• Terminal illness with expected survival of less than 12 months.
• Currently enrolled in a trial that does not permit co-enrollment.
• Declined to provide informed consent.
• Unable to obtain informed consent due to language barriers.
• Unable to obtain informed consent because a legally authorized representative (LAR) was unavailable.
• Anticipated problems, in the judgment of research personnel, with maintaining follow-up with the patient.
• Prior enrollment in the trial.
• Eligible patient or LAR was not approached within screening window (missed participant).
• Other reason to exclude the patient, as approved by the Principal Investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Procedure: Accelerated Flap Coverage Surgery; Activation of the accelerated flap pathway with a goal flap time of <72h from injury
Active Comparator: 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.	Procedure: Standard of Care Flap Timing; Flap timing at the standard of care timing for the clinical site

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Status	Clinical status is a hierarchical composite of the following outcomes: 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)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	All-cause mortality. Mortality will be time-to-event, with the assumption that earlier is worse than later.	6 and 12 months
Amputation	Amputation related to injury. Amputation will be time-to-event, with the assumption that earlier is worse than later.	6 and 12 months
Unplanned re-operation	Unplanned re-operation for infection and/or flap complication (flap compromise, partial and/or complete flap failure). Re-operation for infection and flap complication will account for more than one operation, with the assumption that more is worse than less.	6 and 12 months
Number of days in hospital	Days in an acute in-patient hospital (i.e., not rehab or nursing facility)	6 and 12 months
Patient-reported health status as assessed by the Euro-QoL (EQ-5D-5L)	Patient-reported health status as assessed by the EQ-5D-5L. The EQ-5D-5L is scored on a 0 to 100 mm scale. 0 mm represents "the worst health you can imagine to 100 mm which represents "the best health you can imagine."	6 and 12 months
Quality of life as assessed by the Limb-Q	Health-related quality of life and patient satisfaction measured with the Limb-Q. The Limb-Q is a set of independently functioning scales. All scales are scored 0-100 (higher = better). The Limb-Q Appearance, Physical, Symptoms, Financial Impact, Life Impact, and Psychological scales will be used.	6 and 12 months
Clinical Status	Clinical status is a hierarchical composite of the following outcomes: 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)	12 months

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Investigators: Principal Investigator: Lily HMIR Mundy, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: September 15, 2026
• First Submitted That Met QC Criteria: September 15, 2026
• First Posted (Actual): September 18, 2026

Study Record Updates

• Last Update Posted (Actual): September 18, 2026
• Last Update Submitted That Met QC Criteria: September 15, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: limb salvage; open fracture; flap reconstruction; flap timing; open dislocation
• Additional Relevant MeSH Terms: Wounds and Injuries; Fractures, Bone; Fractures, Open; Leg Injuries
• Other Study ID Numbers: IRB00525377; 1UG3AR085896 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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