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

Peripheral Vascular Disease Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00300040
• Other study ID #: BIOSA001/BIOEU001
• Status: Terminated
• Phase: Phase 2
• First received: March 6, 2006
• Last updated: May 15, 2008
• Start date: May 2006
• Est. completion date: June 2008

Study information

• Verified date: May 2008
• Source: Biopure Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Africa: Medicines Control CouncilUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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%).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: June 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ischemia
• Peripheral Arterial Disease
• Peripheral Vascular Disease
• Peripheral Vascular Diseases
• Vascular Diseases

Intervention

Drug:
• Hemoglobin glutamer 250 - bovine
intravenous - 250ml/dose - 32.5g Hb (Concentration 13 +/- 1g/dL)
• 6% Hydroxyethylstarch
250ml for intravenous infusion

Locations

Country	Name	City	State
South Africa	Johannesburg Hospital	Johannesburg	Guateng
South Africa	Milpark Hospital	Parktown West	Guateng
South Africa	Pretoria Academic Hospital	Pretoria	Guateng
South Africa	University of Stellenbosch	Tygerburg
United Kingdom	John Radcliffe Hospital	Headington	Oxfordshire

Sponsors (1)

Lead Sponsor	Collaborator
Biopure Corporation

Countries where clinical trial is conducted

South Africa,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality at 60 days post amputation procedure		60(±7 days) post-procedure follow-up visit	Yes
Secondary	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	Yes