BACKGROUND: Preclinical studies suggest that administration of cytokines to mobilize stem cells and alter the postinfarction inflammatory cardiac milieu may enhance left ventricular function and survival. METHODS:Eighteen patients were randomized in a 2:1 double-blind fashion to granulocyte colony stimulating factor (G-CSF) (at 5 escalating to 10 microg/kg per day subcutaneously for 5 days [6 patients in each group]) or matching placebo. Principal safety and efficacy end points were rupture-free survival and recovery of left ventricular function, respectively. Mobilization into the systemic circulation of precursor CD34+ and CD117+ stem cells at 30 days were also assessed. RESULTS: Baseline characteristics of the 3 groups were well matched. Mean +/- SD creatine kinase-MB maximum was 349 (169) IU. Follow-up averaged 30 +/- 6, 21 +/- 11, and 11 +/- 6 months in the 3 groups, respectively. Precursor cell mobilization increased by a factor of 5 to 7 in the G-CSF-treated patients. There were no deaths or myocardial ruptures leading to tamponade through 30 days. Baseline and 30-day left ventricular ejection fraction in the placebo, 5-microg, and 10-microg dose groups were 33.7% (1.6) and 41.7% (8.2), 36.8% (7.5) and 41.3% (10.3), and 33.5% (4.8) and 38.7% (7.3), respectively (P = NS for all between-group comparisons). No differences between the G-CSF and placebo groups were noted in any other measure of left ventricular systolic or diastolic function 30 days after infarction. CONCLUSIONS: Despite demonstrated mobilization of precursor stem cells in a timely fashion, in this small, pilot-scale randomized trial involving patients with large myocardial infarction, we were unable to demonstrate improvement in left ventricular function at 30 days.
RCT Entities:
BACKGROUND: Preclinical studies suggest that administration of cytokines to mobilize stem cells and alter the postinfarction inflammatory cardiac milieu may enhance left ventricular function and survival. METHODS: Eighteen patients were randomized in a 2:1 double-blind fashion to granulocyte colony stimulating factor (G-CSF) (at 5 escalating to 10 microg/kg per day subcutaneously for 5 days [6 patients in each group]) or matching placebo. Principal safety and efficacy end points were rupture-free survival and recovery of left ventricular function, respectively. Mobilization into the systemic circulation of precursor CD34+ and CD117+ stem cells at 30 days were also assessed. RESULTS: Baseline characteristics of the 3 groups were well matched. Mean +/- SD creatine kinase-MB maximum was 349 (169) IU. Follow-up averaged 30 +/- 6, 21 +/- 11, and 11 +/- 6 months in the 3 groups, respectively. Precursor cell mobilization increased by a factor of 5 to 7 in the G-CSF-treated patients. There were no deaths or myocardial ruptures leading to tamponade through 30 days. Baseline and 30-day left ventricular ejection fraction in the placebo, 5-microg, and 10-microg dose groups were 33.7% (1.6) and 41.7% (8.2), 36.8% (7.5) and 41.3% (10.3), and 33.5% (4.8) and 38.7% (7.3), respectively (P = NS for all between-group comparisons). No differences between the G-CSF and placebo groups were noted in any other measure of left ventricular systolic or diastolic function 30 days after infarction. CONCLUSIONS: Despite demonstrated mobilization of precursor stem cells in a timely fashion, in this small, pilot-scale randomized trial involving patients with large myocardial infarction, we were unable to demonstrate improvement in left ventricular function at 30 days.
Authors: Benjamin Hibbert; Bradley Hayley; Robert S Beanlands; Michel Le May; Richard Davies; Derek So; Jean-François Marquis; Marino Labinaz; Michael Froeschl; Edward R O'Brien; Ian G Burwash; George A Wells; Ali Pourdjabbar; Trevor Simard; Harold Atkins; Christopher Glover Journal: CMAJ Date: 2014-06-16 Impact factor: 8.262
Authors: Ricardo Sanz-Ruiz; Enrique Gutiérrez Ibañes; Adolfo Villa Arranz; María Eugenia Fernández Santos; Pedro L Sánchez Fernández; Francisco Fernández-Avilés Journal: Stem Cells Int Date: 2010-11-04 Impact factor: 5.443