Clinical trial NCT01758874: Study to Explore the Effect of Lowering Blood Viscosity in Patients With Treatment-resistant Critical Limb Ischemia
Official title: Phase 2 Study to Explore the Effect of Lowering Blood Viscosity in Patients With Treatment-resistant Critical Limb Ischemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Critical Limb Ischemia
Keywords: Critical limb ischemia
Phlebotomy
Amputation
Rutherford classification Grade 3, Category 5 or 6
Fontaine stage IV
Lead sponsor: Seoul Veterans Hospital
Sponsor class: OTHER
First posted: 2013-01-01
Enrollment: 20
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Major amputation rate (limb salvage rate)
timeFrame: 5 year follow-up period
Secondary outcomes:
measure: Time-to-major amputation
timeFrame: 5 year follow-up period
measure: Mortality rate
timeFrame: 5 year follow-up period
measure: Blood viscosity measurements
timeFrame: Conducting study periods (4 weeks)
Other outcomes:
measure: VA pain scale
timeFrame: Conducting study periods (4 weeks)
measure: Ankle-Brachial Index
timeFrame: Conducting study periods (4 weeks)
measure: Complete wound healing
timeFrame: Conducting study periods (4 weeks)
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul Veterans Hospital
Study officials:
affiliation: Seoul Veterans Hospital
name: Doosang Kim, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: