Limb Salvage Through Tissue Engineering: A Novel Treatment Modality Using Dehydrated Human Amnion/Chorion Membrane

Study Overview
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Brief Summary
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Extremity wounds with exposed critical structures, including bone and tendon are a major burden on the American healthcare system with limited treatment options. Free Flap reconstructions of lower extremity wounds have an increased failure rate in comparison to elective free flap procedures.These procedures are long and are associated with a high cost of care, prolonged hospital stays, and are limited by the need for surgical specialist availability and patient vessels suitable for anastomoses. This study will use a new treatment modality which is a commercially ready human amniotic membrane allograft (EpiFix) to promote a granulation tissue wound base that will be suitable for skin grafting, thus forgoing the need for a flap-based for reconstruction. The study goals are to reduce the overall cost of providing definitive treatment by decreasing operative time, length of hospital stay, decrease the need for intensive nursing care and rehabilitation. This study will aim to provide a treatment option that is readily accessible to all patients with these complex wounds in any healthcare setting across the country.

Detailed Description
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53 patients ages 18 and over , presenting with wounds with exposed critical structures (bone and/or tendon) will be enrolled in the study and randomized into one of two groups. 21 patients will be in the standard treatment group (Flap based reconstruction) and 32 patients will be in the dHACM (EpiFix) + skin grafting treatment group (Experimental). Exclusion criteria includes exposed implanted hardware (surgical plates), anticipated need for future surgical procedures through the same wound, wounds resulting from surgical removal of malignancy, and patients who are not free flap candidates. Data will be collected upon enrollment including: Background and demographic information Wound size and severity Pain level Medication use Photographs of wound Flap Reconstruction group (Standard of Care): Patients in this group will have any dead, damaged or infected tissue removed from the wound and a negative pressure wound dressing will be applied until the wound is clean and adequate for flap reconstruction. Following flap reconstruction, patients typically require a 36-48 hour intensive care unit admission for flap monitoring and 5 days to bed rest to allow for proper healing. If the flap is successful, a dangle protocol will occur until patient increases the dependent position. Once the dangle protocol is completed, patients may require inpatient physical/occupational therapy prior to discharge from the hospital. If patient is not healing the physician may discuss other treatment options including crossing over to the EpiFix arm or amputation. EpiFix and Skin Graft group: Patients in this group will have any dead, damaged or infected tissue removed from wound. Once it is free from infection, a thin tissue (EpiFix) will be applied directly to the open wound. This will be covered by sterile wound dressing. After approximately 5-7 days the wound will be assessed for suitability of split thickness skin grafting. If adequately healed, skin grafting will be performed. After 5 days, the graft will be evaluated and if successful, the patient will be discharged home or to a rehab facility. If the wounds are not adequate for skin grafting, additional damaged tissue will removed and EpiFix will be placed until the wound is suitable for grafting. If you do not heal sufficiently the physician will discuss other treatment options including cross over to the standard of care Free Flap or amputation. Study staff will evaluate the wound twice a week for the first 2 weeks, then once a week until 6 weeks. At this point, the patient will be followed every 4 weeks up to 22 weeks. Visits to the clinic will include wound measurements, photos, pain scale and evaluation of any infection.

Official Title
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Limb Salvage Through Tissue Engineering: A Novel Treatment Modality Using Dehydrated Human Amnion/Chorion Membrane

Conditions
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Soft Tissue Injuries, Wounds, Trauma, Injury, Limb Salvage

Intervention / Treatment
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* Device: Dehydrated Human Amnion/Chorion Membrane
* Procedure: Flap-Based Reconstructive Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Wound includes exposed critical structures (tendon and/or bone) Patient is candidate flap reconstruction Patient is candidate for limb salvage Exclusion Criteria: Wound involves weight-bearing surfaces (e.g. heel or forefoot wounds), Exposed implanted hardware (e.g. surgical plates) Anticipated need for future surgical procedures through the same wound Wounds resulting from surgical removal of malignancy Patients who are not flap candidates (e.g. severe peripheral vascular disease) Patients who are not limb salvage candidates (e.g. insensate or ischemic limbs).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Human Amnion/Chorion Membrane + skin graft<br>Dehydrated Human Amnion/Chorion Membrane (dHACM) will be placed on wound at the initial debridement to promote granulation tissue at the wound bed. Approximately 5-7 days following debridement, wound will be assessed for suitability of split thickness skin grafting. If an adequate granulation tissue is present, skin grafting will be performed and assessed for take in 5 days. | Device: Dehydrated Human Amnion/Chorion Membrane<br> <br> * Other names: EpiFix;|
| Active Comparator: Flap Reconstruction (Standard of Care)<br>A negative pressure wound dressing (NPWD) will be applied at the time of debridement until the wound is clean and adequate for flap reconstruction. Flap-based reconstruction is performed. Following flap reconstruction,patient will have 5 days of bed rest to allow proper healing and coverage of the wounds. If flaps are successful, patients starts a limb dangle protocol which gradually increases the dependent position and allows the flap to acclimate to new physiologic demands. Following dangle protocol patient will require inpatient physical and occupational therapy prior to discharge. | Procedure: Flap-Based Reconstructive Surgery<br>* Standard of Care surgical intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment failure | Failure will be defined as a composite of amputation, persistent exposed critical structures, development of osteomyelitis or need for additional flaps within 6 weeks of treatment. Osteomyelitis will be diagnosed as pus from bone requiring long-term (>4 weeks) of IV antibiotics.), Experimental Group: Persistent exposed critical structures in the experimental arm refers to persistence of exposed nerve, blood vessels, bone or tendon after 4 weeks of dHACM treatment Standard of care group: Persistence of exposed nerve, blood vessels, bone or tendon after flap treatment | Within 6 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wound Issue | Were any of the following recorded: wound dehiscence, partial flap loss, or partial skin graft loss requiring prolonged local wound care or other wound treatment (e.g. hyperbaric oxygen therapy, negative pressure wound dressing, other wound devices)? | within 6 months of initial wound closure | 
| Epidermolysis | Was there any diagnosis of epidermolysis during study | within 6 months of initial wound closure | 
| Length of ICU stay | Total number of ICU inpatient days | within 6 months of initial wound closure | 
| Length of inpatient hospital stay | Total number of inpatient hospital days | within 6 months of initial wound closure | 
| Total treatment time from initial treatment to initial closure (excludes treatment of complications) | Total number of days from initial treatment to end of study | within 6 months of initial wound closure | 
| Total treatment time from initial treatment to completion of limb salvage (includes treatment of complications) | Total number of days from initial treatment to completion of limb salvage | within 6 months of initial wound closure | 
| Number of dHACM treatments required | Total number of EpiFix applications | within 6 months of initial wound closure | 
| Death from any cause | Death from any cause | within 6 months of initial wound closure | 
| Deep vein thrombosis diagnosed by radiologic imaging (e.g. ultrasound or CT) | Any diagnosis of DVT during study | within 6 months of initial wound closure | 
| Pulmonary embolus | Any diagnosis of PE during study | within 6 months of initial wound closure | 
| Ventilator-associated pneumonia | Any diagnosis of vent-associated pneumonia | within 6 months of initial wound closure | 
| Number of microsurgical revisions needed (arterial or venous) | Number of microsurgical revisions needed | within 6 months of initial wound closure | 
| Bony non union, bony melanin | Any diagnosis of bony non-union or bony melanin during study | within 6 months of initial wound closure | 
| Tendon rupture | Any diagnosis of tendon rupture during study | within 6 months of initial wound closure |