Abstract 12114: Safety and Efficacy of Sitagliptin plus Granulocyte-colony Stimulating Factor in Patients Suffering From Acute Myocardial Infarction (Sitagrami Trial) - Primary and Secondary Analyses
Introduction: In animal models, we have previously shown that a combined progenitor cell therapy comprising G-CSF treatment and a pharmacological inhibition of DPP4 can enhance the recruitment of circulating progenitor cells (ciPCs) into the ischemic cardiac tissue via the SDF1/CXCR4 signaling. Within the myocardium, these bone marrow-derived cells can mediate local regenerative effects. Mainly via a paracarine action ciPCs thus reduce adverse cardiac remodeling, inhibit apoptosis and enhance heart function and survival.
Due to these promising preclinical results, we transferred our therapeutic concept into the phase III, multi-center, randomized, double blind and placebo-controlled SITAGRAMI trial. The purpose of the study was to assess the therapeutic impact of a combined pharmacological progenitor cell therapy using G-CSF and the DPP4 inhibitor Sitagliptin (G+S) after severe acute myocardial infarction (EudraCT Number: 2007-003941-34; www.clinicaltrials.gov; registration number: NCT00650143).
Methods and Results: The enrolled 174 patients suffered from large myocardial infarction and underwent successful percutaneous coronary intervention within 24 hours after initiation of symptoms. We randomized patients in a 1:1 ratio to a treatment with either placebo or a combination of G-CSF for 5 days and Sitagliptin for 4 weeks. We executed Cardiac MRI in all patients at screening visit and after 6 months and planned additional clinical follow-up visits 6 and 52 weeks after the index event. In our final analysis, placebo treated patients showed a mean change in left ventricular EF after 6 months of 4.6%. This exactly corresponds to the changes reported 6 months after acute myocardial infarction by previously published clinical trials.
Conclusions: Besides the primary endpoint data (change of left and right ventricular ejection fraction (EF) from screening to 6 months of follow-up) and general safety analyses, we will report about various secondary endpoints including cardiac volumes and myocardial perfusion. Furthermore, we will present additional analyses on the occurrence of major adverse cardiac events, in stent restenosis as well as de novo stenosis, gender specific-differences and various subgroup analyses.
Author Disclosures: C. Brenner: Consultant/Advisory Board; Modest; MSD. H.D. Theiss: None. C. Adrion: None. U. Grabmaier: None. D. Theisen: None. F. von Ziegler: None. A. Leber: None. A. Becker: None. H. Sohn: None. E. Hoffmann: None. U. Mansmann: None. G. Steinbeck: None. W. Franz: Consultant/Advisory Board; Modest; MSD.
- © 2015 by American Heart Association, Inc.