Accelerated Flap Coverage in Severe Lower Extremity Trauma

Extremity Fracture Lower Clinical Trial

— FLAP ATTACK  

Official title:

Accelerated Flap Coverage Versus Standard Timing in the Treatment of Severe Lower Extremity Musculoskeletal Injuries

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06293469
• Other study ID #: IRB00434587
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 2024
• Est. completion date: November 2029

Study information

• Verified date: May 2024
• Source: Johns Hopkins University
• Contact: Lily Mundy, MD
• Phone: 410-706-2492
• Email: LMundy3[@]jhu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 356
• Est. completion date: November 2029
• Est. primary completion date: May 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

The inclusion criteria are:

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.

The exclusion criteria are:

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

8. Declined to provide informed consent.

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

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

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

12. Prior enrollment in the trial.

13. Other reason to exclude the patient, as approved by the Methods Centre.

Related Conditions & MeSH terms

• Extremity Fracture Lower
• Fractures, Bone
• Leg Injuries
• Open Tibia Fracture
• Tibial Fractures

Intervention

Procedure:
• Accelerated Flap Coverage Surgery
Timing of the flap surgery is with a goal of 72 hours from injury
• Standard of Care Flap Timing
Timing of the flap surgery is the standard of care flap timing for the participating institution.

Locations

Country	Name	City	State
Australia	The Alfred Hospital	Melbourne	Victoria
Spain	Vall d'Hebron University Hospital	Barcelona
United States	John Hopkins Bayview Medical Center	Baltimore	Maryland
United States	R Adams Cowley Shock Trauma Center	Baltimore	Maryland
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Oregon Health & Science University	Portland	Oregon
United States	UC Davis Medical Center	Sacramento	California

Sponsors (5)

Lead Sponsor	Collaborator
Johns Hopkins University	Foundation of Orthopedic Trauma, McMaster University, Orthopaedic Trauma Association, University of Maryland, Baltimore

Countries where clinical trial is conducted

United States,  Australia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical status	Clinical status is a hierarchical composite of the following outcomes: All-cause mortality; Amputation related to injury; Re-operation for infection and/or flap complication (flap compromise, partial and/or complete flap failure); Days in hospital, defined as days in an acute in-patient hospital (i.e., not rehab or nursing facility)	6 months
Secondary	Mortality	All-cause mortality	6 months and 12 months
Secondary	Amputation	Amputation related to injury. Amputation will be time-to-event, with the assumption that earlier is worse than later.	6 months and 12 months
Secondary	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 be time-to-event, with the assumption that earlier is worse than later. Re-operation for infection and major flap complication will account for more than one operation, assuming that more operations are worse.	6 months and 12 months
Secondary	Number of days in hospital	Days in an acute in-patient hospital (i.e., not rehab or nursing facility)	6 months and 12 months
Secondary	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 months and 12 months