Stem cell injections can induce neovascularisation and thereby increase the perfusion of ischaemic organs, Amann told delegates. “The object of the study was to evaluate the therapeutic value of stem cell-induced angiogenesis and arteriogenesis in no-option critical limb ischaemia and to provide a prespecified interim safety/efficacy analysis of 47 patients,” he said. The trial was an investigator-initiated, double-blinded, 1:1 randomised, placebo-controlled multicentre study at taking place at four sites in Germany (Berlin, Karlsbad, Trier and Boppard) including 90 critical limb ischaemia patients with no further option for revascularisation.
Forty five subjects were randomised to autologous bone marrow stem cells which were injected in 40–60 sites intramuscularly into the ischaemic limb and 45 placebo subjects underwent a sham bone marrow puncture and 40–60 placebo injections.
Primary endpoints after three months were major amputation and persisting critical limb ischaemia. Secondary endpoints were death, ABI/tcpO2, wound healing, quality of life, major adverse cardiac events, walking distance, minor amputations and angiography.
Forty seven patients were analysed. Demographic and clinical characteristics were identical in the cell (n=6) and placebo group (n=21); age 74±12 yrs), diabetes (64%), smoking (44%), wound size (7cm2±9), baseline ABI (0,40±0.1), and tcpO2 (13±13). Rutherford categories were 4:17%, 5: 79%, 6: 4%, and the number of previous unsuccessful revascularisations of the index leg was 2.1 per patient.
At three months, a significant clinical improvement in Rutherford category occurred in the stem cell group (baseline/3 months 4.9/4.3, p<0.05). There was no change in the placebo group (4,9/4.9).
Major amputations were done in 12% (3/26) in the stem cell group, and in 24% (5/21) of the placebo group. TcPo2 doubled in the stem cell group (12/25mmHg). ABI increased trendwise (p.06) from 0.40 to 0.48 in the stem cell group; there was no change in the placebo group. Bone marrow aspiration and injection had no procedure related adverse effects. “Complete results of the study will be available in early 2011,” Amann said.
Bone marrow (or sham) aspiration was carried out by an independent aspirator. Bone marrow was processed in a closed, automated cell manufacturing system for 12 days to expand the number of stem and progenitor cells. 136 ± 41 x 106 total viable cells of which 25 ± 10 x 10⁶ were CD90+ or electrolyte (placebo) solution were injected into the ischaemic lower extremity and foot. Primary safety endpoints were incidence of adverse events or serious adverse events. Clinical endpoints included Kaplan Meier estimation of treatment failure defined as a composite of major amputation, development of gangrene, and/or doubling of wound size. Change from baseline in pain assessment by a 10cm visual analogue scale, as well as amputation rates and wound healing were evaluated.
Randomisation ratio was approximately 2:1, tissue repair cell group (n=32) vs. placebo (n=14). Mean age was 68 years (range 34–85 years), 72% male and 50% diabetic with no notable demographic differences and no difference in adverse or serious adverse events between the groups.
The composite endpoint of time to treatment failure showed a significant difference favouring tissue repair cell treatment (log-rank test, p=0.009). At six months major amputation occurred in 19% of tissue repair cell treated patients vs. 43% of placebo (p=0.14).
“There was a trend favouring tissue repair cell treated patients in complete wound healing after 12 months follow-up with one patient death in each group. A meaningful difference in pain assessments between the groups was not observed,” Powell concluded.
