Autologous bone marrow cells in patients with critical limb ischemia

• Register: ISRCTN
• Last refreshed on: 28 August 2017
• Main ID: ISRCTN16096154
• Date of registration: 26/07/2016
• Prospective Registration: No
• Primary sponsor: National Institute of Heart and Vascular Diseases
• Public title: Autologous bone marrow cells in patients with critical limb ischemia
• Scientific title: Transplantation of autologous bone marrow cells in patients with no-option critical limb ischemia
• Date of first enrolment: 01/10/2009
• Target sample size: 62
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN16096154
• Study type: Interventional
• Study design: Single-centre randomised parallel trial (Treatment)

Countries of recruitment

Slovakia

Contacts

• Name: Juraj Madaric

Key inclusion & exclusion criteria

Inclusion criteria: 1. Patients over 18 years of age
2. With ischemic skin lesions (ulcers or gangrene) with a Critical limb ischemia Rutherford category of 5 or 6 according to the TransAtlantic InterSociety Consensus (TASC) classification (minor or major tissue loss)
3. Critical limb ischemia defined by ankle–brachial index =0.4, or ankle systolic pressure <50 mmHg, or toe systolic pressure <30 mmHg, or transcutaneous oxygen pressure (tcpO2) <30 mmHg
4. No option for endovascular or surgical revascularization assessed by a vascular surgeon and interventionalist
5. Failed revascularization defined as no change of clinical status with the best standard care 4 weeks after endovascular or surgical revascularization
Exclusion criteria: 1. Life expectancy <6 months
2. Evidence of malignancy during last 5 years
3. Proliferative retinopathy
4. Critical coronary artery disease or unstable angina pectoris
5. End-stage kidney disease and patient on dialysis
6. Bone-marrow disease (e.g., myelodysplastic syndrome, severe anemia, leukopenia, thrombocytopenia)

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Critical limb ischemia
Circulatory System
Critical limb ischemia

Intervention(s)

Participants are randomised into two groups by computer randomization program (local IM BMCs administration versus selective IA infusion, 1:1) with equal sex distribution and equal distribution of patients with diabetes in both groups.

Method of BMC isolation – both study arms: Isolation of stem cells is realized under analgosedation with propofol. A total of 240 mL of bone marrow from both posterior iliac crests is harvested using a standard disposable needle for bone-marrow aspiration. Bone-marrow aspirate was processed using a SmartPreP2 Bone Marrow Aspirate Concentrate System (Harvest, Plymouth, MA, USA), which uses gradient density centrifugation to provide 40 mL of bone marrow-rich product for all blood elements within 15 minutes.

Immediately after stem cells harvest and centrifugation, bone marrow cell (MBC) product is administered either intramuscularly (Group A) or intraarterially (group B).

Group A: Immediately after the harvesting and centrifugation of stem cells, in group A, 40 mL of BMCs is administrates under analgosedation with propofol by deep injections with a 23-G needle into the muscles of the affected limb along the crural arteries, with each injection being approximately 1 mL.

Group B: Intraarterial injection (IA) injection of 40 mL of BMCs is realized from a percutaneous retrograde contralateral femoral approach or antegrade femoral approach under local anesthesia at the site of arterial occlusion of the affected limb using a 4-F catheter at 800 mL/h.

The length of procedure in both groups is approximately one hour.

Patients are discharged the day after the procedure on dual antiplatelet therapy (aspirin and clopidogrel) and statin therapy. All patients receive conventional wound care during follow-up of 12 months.

Primary Outcome(s)

Combined end-point of limb salvage and wound healing is measured at 12 months. Wound characteristics are documented by digital photography. Wound healing is evaluated by two independent physicians.

Secondary Outcome(s)

1. Mortality is assessed at 12 months follow-up. In case of absence of patients at regular follow-up control, the family of patient is contacted.
2. Amputation free survival is measured by clinical assessment at 12 months.
3. Major limb amputation rate is measured by clinical assessment at 12 months.
4. Limb perfusion is determined by measuring transcutaneous oxygen pressure (tcpO2) of the affected limb at baseline, 6 months, and 12 months. TcpO2 is measured using a TCM400 Mk2 monitor (Radiometer Medical ApS, Copenhagen, Denmark), at the forefoot in the supine position with an electrode temperature of 44°C.
5. Severity of limb ischemia is determined using the Rutherford classification at baseline, 6 months, and 12 months.
6. Severity of limb ischemia is determined using the ankle brachial index (ABI) assessment at baseline, 6 months, and 12 months. Measurement of the resting ankle–brachial index (ABI) is realized according to validated standards. It is calculated as the quotient of the highest ankle pressure and highest brachial systolic blood pressure (normal values, 0.95–1.2).
7. Pain scale is measured using a visual analog scale (VAS) graded form 0 to 10, at baseline, 6 months, and 12 months
8. Quality of life at 6 months and 12 months after BMC application is assessed by the EuroQol questionnaire. Using a VAS, patients rate their overall health status from 0 (“worst”) to 100 (“best”) imaginable health.
9. Wound size is measured in cm2 at baseline, 6 months, and 12 months. Wound characteristics are documented by digital photography. Wound healing is evaluated by two independent physicians.

Secondary ID(s)

24209

Source(s) of Monetary Support

European Regional Development Fund