Surgical Evaluation for Upper Extremity Lymphedema (BioBridge)

Study Overview
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Brief Summary
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To investigate whether the addition of Fibralign's BioBridge® Collagen Matrix (BioBridge) devices to the standard surgery for vascularized lymph node transfer will improve the outcome of surgical treatment in lymphedema of the upper arm.

Detailed Description
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The proposed study utilizes Fibralign's BioBridge® Collagen Matrix (BioBridge), a sterile implantable biocompatible and biodegradable surgical mesh ribbon comprised of highly purified porcine collagen. The Class II device was cleared by CDRH Division of Surgical Devices on 8 January 2016 under 510(k) K151083. The study will investigate whether addition of the BioBridge Collagen Matrix to the standard surgery for vascularized lymph node transfer will improve the outcome of surgical treatment in lymphedema of the upper extremity. This clinical study will also be used in support of IDE G200200 review conducted by the FDA. Primary endpoint is the post surgical % change in excess limb volume, measured at 12 months following the surgical procedure. Secondary endpoints are change in quality of life scores measured by LLIS and change in lymphatic function as measured by indocyanine green (ICG) fluorescence imaging.

Official Title
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Prospective Evaluation of Nanofibrillar Collagen Scaffold (BioBridge®) as an Adjunct to Lymph Node Transplant for Upper Extremity Lymphedema

Conditions
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Edema, Lymphedema

Intervention / Treatment
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* Device: BioBridge® Collagen Matrix
* Procedure: Vascularized Lymph Node Transfer (VLNT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject must be a breast cancer survivor, at least 3 years beyond completion of cancer therapy, free of clinical disease, and eligible for surgical intervention. Participants who are not able to safely undergo general anesthesia and/or perioperative care for VLNT are excluded. Ages 18 to 75 years (inclusive) Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2 Life expectancy > 2 years Acquired (secondary) upper limb lymphedema secondary to breast cancer treatment The participant must be eligible for surgical intervention Swelling of 1 limb that is not completely reversed by elevation or compression Stage I-II lymphedema at screening, based on the International Society of Lymphology (ISL) staging system Participants must have no evidence of disease (NED), have completed breast cancer therapy 3 years prior to enrollment; use of endocrine therapy is allowed. Completion of a full course of complete decongestive therapy (CDT), according to ISL guidelines at least 12 weeks prior to screening, including use of compression garments for at least 12 weeks without change in regimen Willingness to comply with recommended regimen of self care, with consistent use of compression garments from screening through the entire study duration (through the safety follow up visit), excluding the first 3 weeks postoperatively where patients are required to not wear compression. Self bandaging, use of nighttime compression garments, and intermittent pneumatic compression devices are allowed, but the procedures and regimens are expected to remain consistent from screening though the entire study duration. Consistent use of an appropriately sized compression garment for daytime use. Limb volume (LV) in the affected limb and unaffected limb must be at least 10% of each other. Evidence of abnormal bioimpedance ratio, if feasible, based upon unilateral disease: L Dex > 10 units. Willingness and ability to comply with all study procedures, including measurement of skin biopsy, and preoperative and postoperative imaging studies. Willingness and ability to understand, and to sign a written informed consent form document Exclusion Criteria: Edema arising from increased capillary filtration will be excluded (venous incompetence). Inability to safely undergo general anesthesia and/or perioperative care related to vascularized lymph node transfer Concurrent participation in a clinical trial of any other investigational drug or therapy, regardless of indication, within 1 month before screening or 5 times the drug's half life, whichever is longer Recent initiation (≤ 12 weeks) of CDPT for lymphedema Other medical condition that could lead to acute limb edema, such as (but not limited to) acute venous thrombosis or heart failure Other medical condition that could result in symptoms overlapping those of lymphedema in the affected limb (eg, pain, swelling, decreased range of motion) History of clotting disorder (hypercoagulable state) Chronic (persistent) infection in the affected limb Infection of the lymphedema limb within 1 month prior to screening Currently receiving chemotherapy or radiation therapy Current evidence, or a history of malignancy within the past 3 years (except for non melanoma skin cancer or cervical cancer in situ treated with curative intent). If the participant has undergone cancer treatment, this must have been completed > 3 years prior to enrollment. Significant or chronic renal insufficiency (defined as serum creatinine > 2.5 mg/dL or an estimated glomerular filtration rate [eGFR] < 30 mL/min at screening) or requires dialytic support Hepatic dysfunction, defined as alanine transaminase (ALT) or aspartate transaminase (AST) levels > 3 × upper limit of the normal range (ULN) and/or bilirubin level > 2 × ULN at screening Absolute neutrophil count < 1500 mm3 at screening Hemoglobin concentration < 9 g/dL at screening Body Mass Index (BMI) >35 Known sensitivity to porcine products Anaphylaxis to iodine Pregnancy or nursing Substance abuse (such as alcohol or drug abuse) within 6 months prior to screening Any reason (in addition to those listed above) that, in the opinion of the investigator, precludes full participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Interventional Model Description: Prospective, randomized, control arm
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BioBridge treatment group<br>Vascularized Lymph Node Transplant surgery (VLNT) supplemented by BioBridge Collagen Matrix implantation | Device: BioBridge® Collagen Matrix<br>* BioBridge Collagen Matrix (BioBridge) is a sterile implantable bio-compatible and biodegradable surgical mesh ribbon comprised of highly purified porcine collagen. The Class II device was cleared by CDRH Division of Surgical Devices on 8 January 2016 under 510(k) K151083. The device will be used for soft tissue surgical support at the time of vascularized lymph node transplant surgery (VLNT); the device will be used, specifically, for surgical support of the lymphatic component of the soft tissue.<br>Procedure: Vascularized Lymph Node Transfer (VLNT)<br>* Micro-surgical procedure for vascularized lymph node transfer (VLNT)<br>|
| Active Comparator: Control group<br>Vascularized Lymph Node Transplant surgery (VLNT) only | Procedure: Vascularized Lymph Node Transfer (VLNT)<br>* Micro-surgical procedure for vascularized lymph node transfer (VLNT)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Excess limb volume change | Change in % of (excess) limb volume in the intervention group relative to control group | Baseline and 12 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LLIS survey | Lymphedema-specific instrument to measure impairments, activity limitations, and participation restrictions in those living with any extremity lymphedema | Baseline and 12 months after treatment | 
| L-Dex bioimpedance spectroscopy. | Change in the Lymphedema Index (L-Dex) in the intervention group relative to control group. The L-Dex score has the requisite sensitivity and specificity to detect the differences in retained interstitial fluid that might discriminate the therapeutic responses of the treated patients. It has been established that the normal range of the L-Dex score is in the interval from -10 to +10 units; the higher score the more difference is in the retained interstitial fluid between the affected and unaffected limbs. | Baseline and 12 months after treatment | 
| Histology | Change in cutaneous histological architecture. The impact of treatment on the cutaneous histopathology will be evaluated through the use of an empirically derived scoring system and will be performed by a dermatopathologist. | Baseline and 12 months after treatment | 
| ICG fluorescence imaging | Change in lymphatic function assessed by ICG fluorescence imaging | Baseline and 12 months after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphedema, Edema