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

NCT ID: NCT03521258

Last Updated: 2018-05-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

53 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-02-29

Study Completion Date

2019-02-28

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.

Conditions

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Wounds Trauma Injury Limb Salvage Soft Tissue Injuries

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Human Amnion/Chorion Membrane + skin graft

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.

Group Type EXPERIMENTAL

Dehydrated Human Amnion/Chorion Membrane

Intervention Type DEVICE

Flap Reconstruction (Standard of Care)

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.

Group Type ACTIVE_COMPARATOR

Flap-Based Reconstructive Surgery

Intervention Type PROCEDURE

Standard of Care surgical intervention

Interventions

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Dehydrated Human Amnion/Chorion Membrane

Intervention Type DEVICE

Flap-Based Reconstructive Surgery

Standard of Care surgical intervention

Intervention Type PROCEDURE

Other Intervention Names

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human amniotic membrane allograft EpiFix

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).
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Louisiana State University Health Sciences Center in New Orleans

OTHER

Sponsor Role lead

Responsible Party

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Frank Lau, MD

Assistant Professor of Clinical Surgery

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Frank Lau, MD

Role: PRINCIPAL_INVESTIGATOR

Louisiana State University Health Sciences Center - New Orleans

Locations

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Louisiana State University Health Sciences Center - N.O.

New Orleans, Louisiana, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Frank Lau, MD

Role: CONTACT

504-412-1240

Facility Contacts

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Frank Lau, MD

Role: primary

504-412-1240

References

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Kroll SS, Evans GR, Goldberg D, Wang BG, Reece GP, Miller MJ, Robb GL, Baldwin BJ, Schusterman MA. A comparison of resource costs for head and neck reconstruction with free and pectoralis major flaps. Plast Reconstr Surg. 1997 Apr;99(5):1282-6. doi: 10.1097/00006534-199704001-00011.

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Hong S. Reconstructive surgery: lower extremity coverage. In: Plastic Surgery.Vol 4. 3rd ed. Elsevier Inc.; 2013:127-150.

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Colohan S, Saint-Cyr M. Management of lower extremity trauma. In: Plastic Surgery.Vol 4. 3rd ed. Elsevier Inc.; 2013:63-91.

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Chung KC, Saddawi-Konefka D, Haase SC, Kaul G. A cost-utility analysis of amputation versus salvage for Gustilo type IIIB and IIIC open tibial fractures. Plast Reconstr Surg. 2009 Dec;124(6):1965-1973. doi: 10.1097/PRS.0b013e3181bcf156.

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Capla JM, Ceradini DJ, Tepper OM, Callaghan MJ, Bhatt KA, Galiano RD, Levine JP, Gurtner GC. Skin graft vascularization involves precisely regulated regression and replacement of endothelial cells through both angiogenesis and vasculogenesis. Plast Reconstr Surg. 2006 Mar;117(3):836-44. doi: 10.1097/01.prs.0000201459.91559.7f.

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DeFranzo AJ, Argenta LC, Marks MW, Molnar JA, David LR, Webb LX, Ward WG, Teasdall RG. The use of vacuum-assisted closure therapy for the treatment of lower-extremity wounds with exposed bone. Plast Reconstr Surg. 2001 Oct;108(5):1184-91. doi: 10.1097/00006534-200110000-00013.

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Parrett BM, Matros E, Pribaz JJ, Orgill DP. Lower extremity trauma: trends in the management of soft-tissue reconstruction of open tibia-fibula fractures. Plast Reconstr Surg. 2006 Apr;117(4):1315-22; discussion 1323-4. doi: 10.1097/01.prs.0000204959.18136.36.

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Khouri RK, Cooley BC, Kunselman AR, Landis JR, Yeramian P, Ingram D, Natarajan N, Benes CO, Wallemark C. A prospective study of microvascular free-flap surgery and outcome. Plast Reconstr Surg. 1998 Sep;102(3):711-21. doi: 10.1097/00006534-199809030-00015.

Reference Type BACKGROUND
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Stern M. THE GRAFTING OF PRESERVED AMNIOTIC MEMBRANE TO BURNED AND ULCERATED SURFACES, SUBSTITUING SKIN GRAFTS. JAMA. 1913;60(13):973-974.

Reference Type BACKGROUND

Gruss JS, Jirsch DW. Human amniotic membrane: a versatile wound dressing. Can Med Assoc J. 1978 May 20;118(10):1237-46.

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PMID: 647542 (View on PubMed)

Zelen CM, Gould L, Serena TE, Carter MJ, Keller J, Li WW. A prospective, randomised, controlled, multi-centre comparative effectiveness study of healing using dehydrated human amnion/chorion membrane allograft, bioengineered skin substitute or standard of care for treatment of chronic lower extremity diabetic ulcers. Int Wound J. 2015 Dec;12(6):724-32. doi: 10.1111/iwj.12395. Epub 2014 Nov 26.

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Sheikh ES, Sheikh ES, Fetterolf DE. Use of dehydrated human amniotic membrane allografts to promote healing in patients with refractory non healing wounds. Int Wound J. 2014 Dec;11(6):711-7. doi: 10.1111/iwj.12035. Epub 2013 Feb 15.

Reference Type BACKGROUND
PMID: 23409746 (View on PubMed)

Serena TE, Carter MJ, Le LT, Sabo MJ, DiMarco DT; EpiFix VLU Study Group. A multicenter, randomized, controlled clinical trial evaluating the use of dehydrated human amnion/chorion membrane allografts and multilayer compression therapy vs. multilayer compression therapy alone in the treatment of venous leg ulcers. Wound Repair Regen. 2014 Nov-Dec;22(6):688-93. doi: 10.1111/wrr.12227. Epub 2015 Jan 8.

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Lau FH, Hoffman RD, Danos D, Torabi R, Patterson CW, McKendrick AD, Stalder M, Dupin C, Hilaire HS. Regenerative vs flap-based limb salvage: a multi-centered, prospective, randomized controlled trial. Regen Med. 2023 Mar;18(3):207-218. doi: 10.2217/rme-2022-0147. Epub 2023 Feb 16.

Reference Type DERIVED
PMID: 36794542 (View on PubMed)

Other Identifiers

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9167

Identifier Type: -

Identifier Source: org_study_id

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