A Study Comparing V.A.C. Negative Pressure Wound Therapy (NPWT) to Moist Wound Therapy (MWT) in the Treatment of Diabetic Foot Amputation Wounds

A Prospective, Randomized, Multicenter, Parallel Study Comparing V.A.C. Negative Pressure Wound Therapy (NPWT) to Moist Wound Therapy (MWT) in the Treatment of Diabetic Foot Amputation Wounds

The objective of this study is to thoroughly examine the role of V.A.C. NPWT in the further salvage of the diabetic foot once it has undergone partial amputation. To determine this, measures of healing, quality of life, and utilization costs associated with this approach will be analyzed. KCI believes that information obtained from this study will show V.A.C. NPWT can support efforts involving limb salvage of the diabetic foot, helping an effective, cost-efficient healthcare solution.

Primary objective is to compare time required to achieve wound bed preparation between Subjects randomized to receive V.A.C. NPWT or MWT. Subjects with ALL the following are eligible for clinical trial enrollment:

Evidence of therapy controlled diabetes, as defined by the American Diabetes Association (ADA) of HbA1C less than or equal to 10%, within 90 days of screen or at time of screening, greater than or equal to 18 years of age, forefoot amputation less than or equal to 10 days old distal to the transmetatarsal level, not extending beyond the Lisfranc joint, receiving MWT allowed in the protocol for treatment of the study wound, Wound surface area measured as length x width of greater than or equal to 10 cm2, Subject is willing and able to provide written informed consent and comply with follow-up visit schedule and maintain a treatment diary, Adequate nutrition to enable wound healing as evidenced by a prealbumin level of greater than or equal to 16 mg/dl or an albumin level of greater than or equal to 3 g/dl within 7 days of screening or at the screening visit, Adequate perfusion in the affected extremity as evidenced by grade 1 or 2 PVR waveform as confirmed at screening, Non-pregnant female Subject of childbearing potential confirmed negative by serum HCG or surgically sterilized or unable to conceive.

Inclusion Criteria:

• Evidence of therapy controlled diabetes, as defined by the American Diabetes Association (ADA) of HgbA1C ≤10%, within 90 days of screening or at time of screening

• ≥18 years of age

• Forefoot amputation ≤ 8 days old distal to the transmetatarsal level, not extending beyond the Lisfranc's joint

• Receiving MWT allowed in the protocol for treatment of the study wound Protocol: V.A.C. 2006-19 Version 1.10 14 November 2007 Confidential/Proprietary Property of KCI, Inc. 28

• Wound surface area, measured as length x width, of ≥10 cm2

• Subject is willing and able to provide written informed consent, comply with follow-up visit schedule, and maintain a treatment diary

• Adequate nutrition to enable wound healing as evidenced by a pre-albumin level of

  ≥16 mg/dl or an albumin level of ≥3g/dl within 7 days of screening or at the screening visit

• Adequate perfusion in the affected extremity as evidenced by Grade 1 or 2 PVR waveform as confirmed at screening (see Section 7.1)

• Non-pregnant female Subject of child-bearing potential (confirmed negative by serum hCG), surgically sterilized, or unable to conceive

Exclusion Criteria:

• Untreated or refractory cellulitis of the wound with periwound erythema ≥3 cm
• Untreated or refractory osteomyelitis of the wound
• Untreated or refractory infection of the wound
• Exposed blood vessels in or around the wound
• Surgical revascularization of the affected extremity ≤10 days from study enrollment other than by percutaneous means
• Percutaneous revascularization of the affected extremity ≤2 days from study enrollment
• Grade 3-5 PVR waveforms
• Long-term (≥30 days) use of steroids (NOTE: Use of non-wound-indicated topical, optical or aerosol types of steroids are permitted at screening and throughout the clinical trial)
• Active Charcot disease of either lower extremity that will interfere with wound treatment
• Malignancy in the wound, around margins or any other malignancy requiring immunosuppressant therapy or chemotherapy
• Presence of necrotic tissue with eschar or slough that cannot be debrided
• Persistent periwound maceration of >96 hours
• Inadequate wound hemostasis that might impair wound healing
• Reported alcohol or drug abuse within the past 6 months
• Topical hypersensitivity or allergy to any disposable component of the V.A.C.® Protocol: V.A.C. 2006-19 Version 1.10 14 November 2007 Confidential/Proprietary Property of KCI, Inc. 29 NPWT System or to tape, dressings, or adhesives
• Female patients with plans to become pregnant during the study period
• Physical (i.e., venous sclerosis) or mental inability to undergo venipuncture for laboratory specimen collection
• Previous participation in this clinical study (VAC 2006-19)
• Participation in any other clinical study ≤30 days of enrollment
• Severe skin conditions (e.g. Meleney's ulcer, scleroderma) that may impair wound healing
• Connective tissue disease or collagen vascular disease (e.g. Ehlers-Danlos syndrome, systemic lupus erythematosus, rheumatoid arthritis) that may impair wound healing
• Hematological disorders or conditions (e.g. polycythemia vera, thrombocythemia, sickle-cell disease) that may impair wound healing
• History of clinically significant chronic anemia as evidenced by a hemoglobin concentration of <10.0 g/dL within ≤30 days of screening
• Severe venous insufficiency (with or without the presence of venous leg ulcers) that may impair wound healing
• Use of V.A.C.® NPWT System to the study wound ≤8 days prior to screening
• Use of any other suction device on the study wound within ≤8 days prior to screening
• Use of normothermic therapy (Warm-UP®) ≤8 days prior to screening
• Use of hyperbaric oxygen therapy (HBO) ≤30 days prior to screening
• Application of recombinant or autologous growth factors (e.g. Regranex® or Procuren®) on the study wound ≤8 days prior to screening
• Application of skin or dermal substitutes and dressings with living cells capable of producing growth factors (e.g. Oasis®, Apligraf®, Dermagraft