Safety/Feasibility Study of HBOC-201 in Amputation at/Below Knee From Critical Lower Limb Ischemia

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the safety and feasibility of HBOC-201 in increasing adequate wound healing in patients with severe peripheral vascular disease who are undergoing lower limb amputation. The hypothesis is that HBOC-201 will pass through the partially occluded lesions in the peripheral arteries in the lower extremity and promote the wound healing process by delivering oxygen to the oxygen deprived tissues. This will reduce the incidence of lower limb wound complications at 60 days post-surgery and may reduce the incidence of a second amputation.

Detailed Description
-----------------
This is a Phase II, single-blinded, prospectively randomized, parallel-group, placebo controlled study that will evaluate the safety and feasibility of HBOC-201 when administered therapeutically to patients with a peripheral vascular occlusive disorder and who are undergoing lower limb amputation due to critical lower limb ischemia. Subjects will be randomized (1:1) to receive either HBOC-201 or a colloid control (HAES-steril® 6%).

Official Title
-----------------
Phase II, Multi-Center,Single-Blind,Placebo-Controlled Study,Evaluating Safety & Feasibility of HBOC-201 (Wound Healing Patients With Peripheral Vascular Disease & Undergoing Lower Limb Amputation Due to Critical Lower Limb Ischemia

Conditions
-----------------
Peripheral Vascular Disease

Intervention / Treatment
-----------------
* Drug: Hemoglobin glutamer 250 - bovine
* Drug: 6% Hydroxyethylstarch


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects ≥ 18 ≤ 75 years of age Scheduled amputation at or above ankle joint, or a more proximal location but below or through the knee joint Documented severe lower extremity peripheral artery occlusive disease confirmed by clinical symptoms of critical limb ischemia and: Frankly gangrenous tissue that merits amputation or Angiographic evidence of occlusive peripheral artery disease within one month of screening Participant or legal representative signs informed consent Willingness to follow study instructions and follow-up visits Exclusion Criteria: No informed consent is obtained If medically inappropriate to administer 250 mL colloidal solution daily for 4 consecutive days Uncontrolled hypertension (BP > 160/90 mm Hg) despite 2 antihypertensive meds or BP > 180/100 mm Hg if untreated Severe liver dysfunction defined by Total Bilirubin > 3 mg/dL or twice the normal limit of serum AST or ALT Symptomatic CVD diagnosed w/ in last 6 months or known high grade carotid stenosis Any severe or unstable medical condition that might interfere w/ the evaluation of study medication Cardiogenic shock (cardiac index < 2 L/min/m2, PCWP > 18 mm Hg) Amputation above knee joint or below ankle joint Any amputation whereby primary skin closure not technically feasible Candidate for percutaneous or surgical revascularization Cardiac failure defined by a NY class III/IV or left ventricular ejection fraction < 30% Life expectancy < 60 days Systemic mastocytosis Previously demonstrated beef product allergy Myocardial infarction w/ in 30 days Participation in another trial w/ in last 30 days Woman who is pregnant or breastfeeding Amputation with known infection at site of skin closure Renal dysfunction requiring dialysis, or serum creatinine level 2.5 mg/dL Peripheral vascular occlusion from cardio arterial emboli Uncontrolled diabetes blood glucose ≥ 400 mg/dL

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Hemoglobin glutamer 250 - bovine | Drug: Hemoglobin glutamer 250 - bovine<br>* intravenous - 250ml/dose - 32.5g Hb (Concentration 13 +/- 1g/dL)<br>* Other names: HBOC-201;|
| Active Comparator: 2<br>6% Hydroxyethylstarch | Drug: 6% Hydroxyethylstarch<br>* 250ml for intravenous infusion<br>* Other names: HAES-steril®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at 60 days post amputation procedure |  | 60(±7 days) post-procedure follow-up visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30 day follow up mortality; Complete wound healing 30, 60 day follow up; Time to complete wound healing; Re-amputation 60 days; Hospital, ICU & rehab days; TcPO2 change; Quality of Life; Delayed wound healing/complications; Rehospitalization; Surgeries |  | 15(±3 days) , 30(±7 days) and 60(±7 days) post-procedure follow-up visits | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Amputation, Lower limb, Critical Limb Ischemia, residual limb, Peripheral Vascular Disease, re-amputation, Lower Limb Ischemia, PVD