Amnioband and Standard of Care vs. Standard of Care Alone in the Treatment of Venous Leg Ulcers

Lower extremity ulcers pose significant clinical, humanistic and economic burdens on society. Millions of Americans are afflicted with painful, open, draining sores on their lower extremities. These sores are referred to as venous leg ulcerations (VLUs).1-5 Under the best of circumstances these ulcers require weeks or months to heal. Not uncommonly wound care specialists see patients who have suffered for years or faced amputation of the limb as their only option to alleviate the pain.

Standard of care will result in healing in 50% of venous leg ulcers in 12 weeks. However, roughly half of patients suffering from venous ulcers will require advanced therapy. Human amniotic membrane replaces the damaged extracellular matrix characteristic of chronic ulcers. In addition, it contains cytokines that may accelerate healing. In clinical practice and recent studies, Dehydrated Human Amniotic Membrane has appeared to be as effective as bioengineered skin products. This RCT is designed to evaluate Amnioband Dehydrated Human Amniotic Membrane in venous leg ulcers.

This study is a multi-center, randomized, trial designed to evaluate the safety and effectiveness of Amnioband Dehydrated Human Amniotic Membrane plus multi-layer compression therapy versus multi-layer compression alone in the healing of venous leg ulcers.

The Standard of Care therapy in this study is multi-layer compression therapy. A number of compression bandaging systems are commercially available. The choice of compression will be at the discretion of the principle investigator.

The Screening Phase (1-14 days) consists of a series of screening assessments designed to determine eligibility followed by, for those who meet the eligibility criteria (described in more detail below), At or up to 14 days before the first Screening Period Visit (S1), written informed consent from the subject will be obtained by the Investigator or suitably qualified designee before the performance of any other protocol-specific procedure.

Subjects who have not been treated with compression therapy for the target ulcer must receive a minimum of 14 days of compression prior to enrollment.

At the first Screening Period Visit (S1), the Investigator will select the study (target) ulcer. Each subject will have only one VLU selected as the study (target) ulcer. In the situation where a subject has more than one VLU at the S1 visit, the Investigator will select the largest VLU that meets the eligibility criteria of the protocol as the study (target) ulcer.

The Screening Period is designed to determine whether subjects are eligible to proceed to the Treatment Period of the study.

The Treatment Phase (12 Weeks) begins with a series of assessments designed to confirm the subjects' continued eligibility. Subjects who continue to meet eligibility criteria will be randomized to one of three groups: (1) standard of care: multi-layer compression (2) weekly application of Amnioband Dehydrated Human Amniotic Membrane (3) biweekly applications of Amnioband Dehydrated Human Amniotic Membrane.

During the Treatment Phase, subjects will be evaluated on a weekly basis. Efficacy evaluations each week will include Investigator assessment of ulcer healing and measurements of ulcer size using a digital camera device. Safety evaluations during the Treatment Phase will consist of adverse event assessments at each visit.

Subjects in any of the three groups whose ulcers do not achieve closure at 12 weeks will be deemed treatment failures. Subjects in the control arm may cross over to the Amnioband arm if they fail to achieve closure although these subjects will not be included in the analysis.

Eligibility Criteria:
Inclusion Criteria:

1. At least 18 years old.
2. Ankle Brachial Pressure Index (ABI) \> 0.75 OR SPP \> 30 mmHg OR TCOM \> 30 mmHg.\*
3. Presence of a venous leg ulcer extending through the full thickness of the skin but not down to muscle, tendon or bone.
4. The largest ulcer will be designated the index ulcer and the only one included in the study. If other ulcerations are present on the same leg they have to be more than 2 cm apart from the index ulcer.
5. Study ulcer (i.e. current episode of ulceration) has been present for greater than one month prior to the initial screening visit, and has failed to respond to documented conservative measures for greater than (1) one month duration and is excluded if it has undergone 12 months of continuous high strength compression therapy over its duration.
6. Study ulcer is a minimum of 2 cm2 and a maximum of 20 cm2 at the randomization visit.
7. The target ulcer has been treated with compression therapy for at least 14 days prior to randomization.
8. Ulcer has a clean, granulating base with minimal adherent slough at the randomization visit.
9. Females of childbearing potential must be willing to use acceptable methods of contraception (birth control pills, barriers, or abstinence).
10. Subject understands and is willing to participate in the clinical study and can comply with weekly visits and the follow-up regimen.
11. Subject has read and signed the IRB/IEC approved Informed Consent Form before screening procedures are undertaken.

Exclusion Criteria:

1. Study ulcer(s) deemed by the investigator to be caused by a medical condition other than venous insufficiency.
2. Study ulcer exhibits clinical signs and symptoms of infection.
3. Known allergy to the components of the multi-layer compression bandaging, or who cannot tolerate multi-layer compression therapy.
4. Study ulcer, in the opinion of the investigator, is suspicious for cancer should undergo an ulcer biopsy to rule out a carcinoma of the ulcer.
5. Subjects with a history of more than two weeks treatment with immunosuppressants (including systemic corticosteroids), cytotoxic chemotherapy, or application of topical steroids to the ulcer surface within one month prior to initial screening, or who receive such medications during the screening period, or who are anticipated to require such medications during the course of the study.
6. Subjects on any investigational drug(s) or therapeutic device(s) within 30 days preceding Screening.
7. Study ulcer improving greater than 30% during the screening phase if the subject was not in adequate compression 14 days prior to screening.
8. History of drug or alcohol abuse.
9. History of radiation at the ulcer site.
10. Presence of one or more medical conditions, as determined by medical history, hematologic, active auto-immune or immune diseases that, in the opinion of the Investigator, would make the subject an inappropriate candidate for this ulcer healing study.
11. History of having Acquired Immunodeficiency Syndrome (AIDS) or HIV.
12. Study ulcer has been previously treated with tissue engineered materials (e.g. Apligraf® or Dermagraft®) or other scaffold materials (e.g. Oasis, Matristem) within the last 30 days
13. Study ulcer requiring negative pressure wound therapy or hyperbaric oxygen during the course of the trial.
14. Presence of any condition(s) which seriously compromises the subject's ability to complete this study, or has a known history of poor adherence with medical treatment.
15. Ulcers on the dorsum of the foot or with more than 50% of the ulcer below the malleolus are excluded.
16. Pregnant or breast feeding.
17. Presence of diabetes with poor metabolic control as documented with a HgA1c \> 12.0 within last 90 days
18. Patients with renal dysfunction whose serum creatinine levels are 3.0mg/dl or greater within the last 90 days
19. History of usage of tobacco products within the last 30 days
20. History of Liver disease with active Cirrhosis of the liver