Study to Explore the Effect of Lowering Blood Viscosity in Patients With Treatment-resistant Critical Limb Ischemia

NCT ID: NCT01758874

Last Updated: 2013-01-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2012-04-30

Brief Summary

PAD is caused by an increased flow resistance in atherosclerotic ischemic limbs. The investigators hypothesize that reducing blood viscosity (through controlled phlebotomy), thereby increasing the deformability of red blood cells, should reduce the flow resistance and improve tissue perfusion leading to improved clinical function and a reduction in symptoms.

Preliminary data demonstrates that phlebotomy causes a measurable change in blood viscosity as measured by the home-made rheologic method.

To evaluate the effectiveness of changes in blood viscosity, obtained through controlled phlebotomy, as a therapy to improve functional status associated with atherosclerotic ischemic limbs in pre-amputation patients.

Detailed Description

The first study is a pilot study and will act as proof of principle. This first study will include 20 patients divided into 2 groups on the basis of a randomized controlled trial: 10 patients in the control group receiving conventional treatment and 10 patients receiving therapeutic phlebotomy to lower blood viscosity. The objective is to evaluate the effect of controlled phlebotomy in patients with Grade 3, Category 5 or 6 chronic critical limb ischemia having tissue loss on Rutherford classification (Fontaine stage IV), end-stage peripheral vascular disease resistant to maximal medical therapy and where revascularization therapy (both percutaneous and surgical) has either proved insufficient or is contra-indicated or declined by the patient, usually resulting in amputation.

The primary outcome parameters will be: the salvage rate of the limb as compared with the salvage rate of the limb with conventional therapy.

Objective classification of improvement in perfusion of the distal extremities using ankle-brachial index (ABI), visual analogue pain scale, and photos.

Subjective classification of improvement in pain scale on critical limbs.

The relationship between alteration in outcome parameters (i.e., the end point is a reduced amputation rate) and blood viscosity will be evaluated as measured by the home-made rheologic methods.

Conditions

Critical Limb Ischemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Non phlebotomy group (control group)

• This control group is the patients who had Rutherford classification Grade 3, Category 5 or 6 (Fontaine stage IV) treatment-resistant chronic critical limb ischemia having tissue loss. They were treated with conventional standard treatment including revascularization operative procedure if feasible, maximum medical treatment with anticoagulation (heparin, low molecular weight heparin, etc), acetylsalicylic acid, cilostazol, and prostaglandin E1, dextran, and pain analgesia with opioid, and finally major amputation.

We records all control arms' amputation, day to amputation, mortality, etc. We will compare amputation and mortality between control and treatment groups.

Non phlebotomy arm has no phlebotomy treatment.

Group Type: NO_INTERVENTION

No interventions assigned to this group

PH (study group)

The patients will be pre-amputation and have Rutherford classification Grade 3, Category 5 or 6 (Fontaine stage IV) treatment-resistant chronic critical limb ischemia having tissue loss.

Procedures for therapeutic phlebotomy

1. Inject heparin 5000 units to prevent blood clot during phlebotomy

2. Inject volume expander equivalent to 5% of blood volume

3. Remove 5% of whole blood

4. Monitor the vital sign of the patient during the phlebotomy

They were treated both phlebotomy and conventional standard management including surgery, medication, amputation, etc.

We will compare amputation and mortality between control and study groups.

Group Type: EXPERIMENTAL

phlebotomy

Intervention Type: PROCEDURE

repeated phlebotomy for 4 weeks

Interventions

phlebotomy

repeated phlebotomy for 4 weeks

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Subjects should have diagnosed Rutherford classification Grade 3, Category 5 or 6 (Fontaine stage IV) treatment-resistant chronic critical limb ischemia having tissue loss, not relieved by maximal medical therapy and they should have exhausted or not be candidates for surgical (other than heart transplant) or percutaneous intervention
• Male
• Age: 18 to 80 years
• Current non-smokers
• BMI >19
• Estimated 6 month survival rate >90%
• Concomitant stable medications will be allowed.
• If the subjects have coronary artery disease established by history, angina pain, EKG, Lab including Troponin I, creatine kinase, lactate dehydrogenase, Echocardiography, Thallium scan or coronary angiography, the subjects should have established a classification of coronary artery involvement by coronary angiography or other procedure with similar precision.

Exclusion Criteria

• Anemia
• Low blood pressure (systolic < 120 mmHg)
• Baseline hematocrit < 30
• Initial whole blood viscosity measurements below 15 miliPoiseille

• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Seoul Veterans Hospital

OTHER

Sponsor Role: lead

Responsible Party

Doosang Kim

Surgeon, M.D.,Ph.D.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Doosang Kim, M.D.,Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Seoul Veterans Hospital

Locations

Seoul Veterans Hospital

Seoul, , South Korea

Countries

South Korea

Other Identifiers

2006-19

Identifier Type: -

Identifier Source: org_study_id