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

NCT01758874 | Completed Phase 2

• 1 other identifier: 2006-19
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Critical Limb Ischemia

Keywords

Critical limb ischemia; Phlebotomy; Amputation; Rutherford classification Grade 3, Category 5 or 6; Fontaine stage IV

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• Time-to-major amputation

  5 year follow-up period

• Mortality rate

  5 year follow-up period

• Blood viscosity measurements

  Conducting study periods (4 weeks)

Other Outcomes (3)

• VA pain scale

  Conducting study periods (4 weeks)

• Ankle-Brachial Index

  Conducting study periods (4 weeks)

• Complete wound healing

  Conducting study periods (4 weeks)

Study Arms (2)

Non phlebotomy group (control group)

NO INTERVENTION

• 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.

PH (study group)

EXPERIMENTAL

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.

Procedure: phlebotomy

Interventions

phlebotomy PROCEDURE

repeated phlebotomy for 4 weeks

PH (study group)

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Seoul Veterans Hospital: lead

Study Sites (1)

Seoul Veterans Hospital

Seoul, 134-060, South Korea

Location

MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia

Interventions

Phlebotomy

Condition Hierarchy (Ancestors)

Peripheral Arterial Disease; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia

Intervention Hierarchy (Ancestors)

Blood Specimen Collection; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Doosang Kim, M.D.,Ph.D.

  Seoul Veterans Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Surgeon, M.D.,Ph.D.

Study Record Dates

• First Submitted: May 14, 2012
• First Posted: January 1, 2013
• Study Start: September 1, 2006
• Primary Completion: April 1, 2007
• Study Completion: April 1, 2012
• Last Updated: January 1, 2013

Record last verified: 2012-12

Locations

KR (1)