Clinical trial NCT06293469: Accelerated Flap Coverage in Severe Lower Extremity Trauma
Official title: Accelerated Flap Coverage Versus Standard Timing in the Treatment of Severe Lower Extremity Musculoskeletal Injuries
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Open Tibia Fracture
Open Dislocation of Ankle
Extremity Fracture Lower
Extremity Injuries Lower
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: McMaster University
name: University of Maryland, Baltimore
name: Orthopaedic Trauma Association
name: Foundation of Orthopedic Trauma
First posted: 2024-03-05
Enrollment: 356
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Clinical status
timeFrame: 6 months
Secondary outcomes:
measure: Mortality
timeFrame: 6 months and 12 months
measure: Amputation
timeFrame: 6 months and 12 months
measure: Unplanned re-operation
timeFrame: 6 months and 12 months
measure: Number of days in hospital
timeFrame: 6 months and 12 months
measure: Quality of life as assessed by the Limb-Q
timeFrame: 6 months and 12 months
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Baltimore
country: United States
facility: R Adams Cowley Shock Trauma Center
state: Maryland
city: Baltimore
country: United States
facility: John Hopkins Bayview Medical Center
state: Maryland
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
Study officials:
affiliation: Johns Hopkins School of Medicine
name: Lily Mundy, MD
role: PRINCIPAL_INVESTIGATOR
References: