scholarly journals Interim analysis results from the RESTORE-CLI, a randomized, double-blind multicenter phase II trial comparing expanded autologous bone marrow-derived tissue repair cells and placebo in patients with critical limb ischemia

2011 ◽  
Vol 54 (4) ◽  
pp. 1032-1041 ◽  
Author(s):  
Richard J. Powell ◽  
Anthony J. Comerota ◽  
Scott A. Berceli ◽  
Raul Guzman ◽  
Timothy D. Henry ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Critical Limb Ischemia ◽  
Interim Analysis ◽  
Tissue Repair ◽  
Phase Ii Trial ◽  
Autologous Bone Marrow ◽  
Limb Ischemia ◽  
Double Blind ◽  
Multicenter Phase ◽  
Autologous Bone

Intraarterial Versus Intramuscular Delivery of Autologous Bone Marrow Blood to Patients with Critical Limb Ischemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2999-2999
Author(s):  
Martin Mistrik ◽  
Juraj Madaric ◽  
Andrej Klepanec ◽  
Ingrid Olejarova ◽  
Marcela Skrakova
Keyword(s):  
Bone Marrow ◽  
Limb Salvage ◽  
Critical Limb Ischemia ◽  
Bone Marrow Aspirate ◽  
Autologous Bone Marrow ◽  
Limb Ischemia ◽  
Pain Scale ◽  
Cd34 Cells ◽  
Autologous Bone ◽  
Bone Marrow Blood

Abstract Abstract 2999 Introduction: Autologous bone marrow cell application has been proposed as an alternative therapy in patients (pts) with critical limb ischemia (CLI), not eligible for endovascular or surgical revascularization, but the way of their administration is currently unresolved. The aim of our study is to compare intramuscular (i.m.) and intraarterial (i.a.) bone marrow blood (BMB) delivery. Methods: Fifty nine patients (median age 67 years, range 38 – 89; gender M :F = 50 :9) with advanced CLI (Rutherford category 5, 6) not eligible for revascularization underwent analgosedation with profolol and total of 240 ml of BMB from both posterior iliac crests were harvested and stabilized with heparin. Bone marrow aspirate was processed with SmartPreP2 Bone Marrow Aspirate Concentrate System (Harvest, Plymouth, MA) – gradient density centrifugation to provide 40 ml of BMB concentrate (BMBc) within 15–20 minutes. Patients were randomized to treatment with 40 ml of BMBc either using local i.m. or i.a. infusion. Primary end points were limb salvage and wound healing. Secondary end points included changes in transcutaneous oxygen pressure (tcpO2), quality of life questionnaire (EQ 5D), ankle-brachial index (ABI), and pain scale (0–10 scale). Patients with limb salvage and wound healing were considered as responders to BMBc therapy. Results: Fifty nine collected BMB contained median mononucleated cell number 35, 8 × 109/l (range 12, 5 – 79, 8) and CD34+ cells 237, 25 × 106/l (range 57, 2 – 694, 3). Processing of BMB reduced to volume from 240 ml to 40 ml (e.g. 6x) and increased concentration of mononucleated cells and CD34+ cells (2, 9x). According to the randomization BMBc was administered i.m. (24 patients) into the ischemic limb or by means of i.a. infusion (800ml/hour) through the catheter positioned into the popliteal artery (25 patients). Since procedure 41 patients could reach 180 days follow up, 4 patients died from unrelated reason to study and 37 patients were evaluable for response. Twenty seven of 37 had limb salvage (73%). There was significant improvement in tcpO2 (15±10 to 29±13mmHg, p<0.001), in pain scale (4.4±2.6 to 0.9±1.4, p<0.001) and EQ 5D (51±15 to 70±13, p<0.001), and significant decrease in Rutherford category of CLI (5.0±0.2 to 4.3±1.6, p<0.01). There were no differences among functional parameters in patients undergoing i.m. versus i.a. delivery. Responders (n=27) vs. nonresponders (n=10) received higher CD34+ cells amounts in the bone marrow concentrate (29±15×10^6 vs 17±12×10^6, p<0.05), but similar number of total nucleated cells (4.3±1.4×10^9 vs 4.1±1.2×10^9, p=0.66). Responders had significantly lower C-reactive protein level (CRP 18±28 vs 100±96 mg/l, p<0.05) and white blood cell counts (8.3±2.1×10^9/l vs 12.3×4.5×10^9/l, p<0.05) at the time of study procedure. Conclusions: Autologous bone marrow blood harvest and administration is safe. There is no difference in i.m. versus i.a. application, both methods of autologous BMB delivery are effective in pts with CLI. Higher CD34+ cell content in BMBc and lower degree of inflammation are associated with good response to BMB application. Funding of project “Transplantation of autologous bone-marrow stem cells in patients with critical limb ischemia” ITMS code 26240220023 is supported by Operational programme Research and Innovation from European Regional Development Fund. Disclosures: No relevant conflicts of interest to declare.

Design and rationale of a randomized, double-blind, placebo-controlled phase III study for autologous bone marrow cell transplantation in critical limb ischemia: the BONe Marrow Outcomes Trial in Critical Limb Ischemia (BONMOT-CLI)

VASA ◽  
2008 ◽  
Vol 37 (4) ◽  
pp. 319-325 ◽  
Author(s):  
Amann ◽  
Lüdemann ◽  
Rückert ◽  
Lawall ◽  
Liesenfeld ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cell ◽  
Critical Limb Ischemia ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Autologous Bone Marrow ◽  
Limb Ischemia ◽  
Major Amputation ◽  
Autologous Bone ◽  
Marrow Cells

Background: Critical limb ischemia (CLI) is the end-stage of peripheral artery disease. Only about two thirds of patients with CLI can be revascularised, one third progresses to leg amputation with high associated morbidity and mortality. Therapeutic angiogenesis with bone marrow cells has shown promising improvement in less severe stages of peripheral ischemia. Our study evaluates the therapeutic value of bone marrow cell induced angiogenesis and arteriogenesis in severe, limb-threatening ischemia. Patients and methods: the BONe Marrow Outcome Trial in Critical Limb Ischemia (BONMOT-CLI) is a investigator-initiated, double-blinded, 1:1 randomized, placebo-controlled multi-centre study at 4 sites in Germany. Only patients with no option for revascularisation or after failed revascularisation will be included. A total of 90 patients is to be included. One arm with 45 subjects will be treated with a concentrate of autologous bone marrow cells which will be injected at 40 sites into the ischemic limb. In the placebo arm, study subjects will undergo a sham bone marrow punction and 40 saline injections. At three months, a combined primary endpoint of major amputation or persisting critical limb ischemia (no clinical or perfusion improvement) will be evaluated. Secondary endpoints are death, changes in perfusion, quality of life, walking distance, minor amputations, wound healing, collateral density and cancer incidence. Post-study follow-up is up to two years. Conclusions: The results of this first randomized placebo-controlled trial for autologous bone marrow cell therapy in CLI will clarify the value of this new therapeutic modality in a patient population with no other alternatives except major amputation.

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