Critical Limb IschemiaPhase 2CLI-PHNCT01758874
Study to Explore the Effect of Lowering Blood Viscosity in Patients With Treatment-resistant Critical Limb Ischemia
A Phase 2 study testing phlebotomy in people with Critical Limb Ischemia, run by Seoul Veterans Hospital at 1 site in South Korea.
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… Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Critical Limb Ischemia
- What is being tested?
- phlebotomy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteSouth Korea
- Study dates
- Sep 2006to Apr 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Anemia
- Low blood pressure (systolic < 120 mmHg)
- Baseline hematocrit < 30
- Initial whole blood viscosity measurements below 15 miliPoiseille
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 2 Study to Explore the Effect of Lowering Blood Viscosity in Patients With Treatment-resistant Critical Limb Ischemia
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.
Read the 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
- Being tested
- phlebotomy
- Keywords
- Critical limb ischemia, Phlebotomy, Amputation, Rutherford classification Grade 3, Category 5 or 6, Fontaine stage IV
- Medical subject headings
- Chronic Limb-Threatening Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
phlebotomyProcedure or surgery
repeated phlebotomy for 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: phlebotomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 5 year follow-up period
Secondary outcomes (3)
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.
Measured: 5 year follow-up period
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.
Measured: 5 year follow-up period
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.
Measured: Conducting study periods (4 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jan 2013 (estimated)
- Study startSep 2006
- Primary completionApr 2007
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Critical Limb IschemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seoul Veterans Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Doosang Kim, Seoul Veterans Hospital
- Investigators
- Doosang Kim, M.D.,Ph.D., Principal investigator, Seoul Veterans Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01758874
- Sponsor's protocol ID
- 2006-19
- Acronym
- CLI-PH
- Status last verified
- Dec 2012
- First submitted
- 14 May 2012
- Last updated
- 1 Jan 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study to Explore the Effect of Lowering Blood Viscosity in Patients With Treatment-resistant Critical Limb Ischemia
- ClinicalTrials.gov ID
- NCT01758874
- Acronym / sponsor ID
- CLI-PH / 2006-19
- Conditions
- Critical Limb Ischemia
- Keywords
- Critical limb ischemia, Phlebotomy, Amputation, Rutherford classification Grade 3, Category 5 or 6, Fontaine stage IV
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Seoul Veterans HospitalUniversity, hospital or other
- Study start
- Sep 2006
- Primary completion
- Apr 2007 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 1 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 | Procedure: phlebotomyThe 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. |
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (4 listed)
- Anemia
- Low blood pressure (systolic < 120 mmHg)
- Baseline hematocrit < 30
- Initial whole blood viscosity measurements below 15 miliPoiseille
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| phlebotomyrepeated phlebotomy for 4 weeks | Procedure or surgery | PH (study group) |
Primary outcome
Major amputation rate (limb salvage rate)
Time frame: 5 year follow-up period
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.
3 secondary outcomes
Time-to-major amputation
Time frame: 5 year follow-up period
Mortality rate
Time frame: 5 year follow-up period
Blood viscosity measurements
Time frame: Conducting study periods (4 weeks)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jan 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Doosang Kim, M.D.,Ph.D. principal investigator
Seoul Veterans Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing phlebotomy in people with Critical Limb Ischemia, run by Seoul Veterans Hospital at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major amputation rate (limb salvage rate) (time frame: 5 year follow-up period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jan 2013.