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

Critical Limb Ischemia Clinical Trial

— CLI-PH  

Official title:

Phase 2 Study to Explore the Effect of Lowering Blood Viscosity in Patients With Treatment-resistant Critical Limb Ischemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01758874
• Other study ID #: 2006-19
• Status: Completed
• Phase: Phase 2
• First received: May 14, 2012
• Last updated: December 27, 2012
• Start date: September 2006
• Est. completion date: April 2012

Study information

• Verified date: December 2012
• Source: Seoul Veterans Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 2012
• Est. primary completion date: April 2007
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Critical Limb Ischemia
• Ischemia

Intervention

Procedure:
• phlebotomy
repeated phlebotomy for 4 weeks

Locations

Country	Name	City	State
Korea, Republic of	Seoul Veterans Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul Veterans Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	VA pain scale	After 4 weeks phlebotomy, we measured and confirmed the VA pain scale improvement or not in study group. They would be the evidences of phlebotomy treatment indirectly.	Conducting study periods (4 weeks)	Yes
Other	Ankle-Brachial Index	After 4 weeks phlebotomy, we measured and confirmed the ABI improvement or not in study group. They would be the evidences of phlebotomy treatment indirectly.	Conducting study periods (4 weeks)	Yes
Other	Complete wound healing	After 4 weeks phlebotomy, we measured and confirmed the complete wound healing (no more discharge from wound and complete epithelialization) between two groups. They would be the evidences of phlebotomy treatment directly.	Conducting study periods (4 weeks)	Yes
Primary	Major amputation rate (limb salvage rate)	The rate of lower limb major amputation (limb salvage rate) was measured in both study arms, during 5 year follow-up period.; They would be the evidences of phlebotomy treatment directly.	5 year follow-up period	Yes
Secondary	Time-to-major amputation	During 5 year follow-up period, we measured the time-to-major amputation between the two groups, phlebotomy study group and control group.; They would be the evidences of phlebotomy treatment directly.	5 year follow-up period	Yes
Secondary	Mortality rate	During 5 year follow-up period, we measured the mortality rate as a final result of a treatment and major amputation between the two groups, phlebotomy study group and control group.; They would be the evidences of phlebotomy treatment directly.	5 year follow-up period	Yes
Secondary	Blood viscosity measurements	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.; Evaluate blood viscosity measurements with the home-made rheologic method as a monitor of and marker for the clinical effectiveness of therapeutic phlebotomy in patients with Rutherford classification Grade 3, Category 5 or 6 (Fontaine stage IV) treatment-resistant chronic critical limb ischemia having tissue loss.	Conducting study periods (4 weeks)	Yes