Sitagliptin plus granulocyte colony-stimulating factor in patients suffering from acute myocardial infarction: A double-blind, randomized placebo-controlled trial of efficacy and safety (SITAGRAMI trial)

• Published in: International journal of cardiology 2016-02, Vol.205, p.23-30
• Main Authors: Brenner, Christoph, Adrion, Christine, Grabmaier, Ulrich, Theisen, Daniel, von Ziegler, Franz, Leber, Alexander, Becker, Alexander, Sohn, Hae-Young, Hoffmann, Ellen, Mansmann, Ulrich, Steinbeck, Gerhard, Franz, Wolfgang-Michael, Theiss, Hans Diogenes
• Format: Article
• Language: English
• Subjects: Acute myocardial infarction; Aged; Cardiovascular; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Granulocyte colony stimulating factor; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - adverse effects; Humans; Male; Middle Aged; Myocardial Infarction - diagnosis; Myocardial Infarction - epidemiology; Myocardial Infarction - therapy; Progenitor cell therapy; Prospective Studies; Sitagliptin; Sitagliptin Phosphate - administration & dosage; Sitagliptin Phosphate - adverse effects; Stem Cell Transplantation - adverse effects; Stem Cell Transplantation - methods; Stroke Volume - drug effects; Stroke Volume - physiology; Treatment Outcome
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2015.11.180

Abstract Objective In animal models, G-CSF based progenitor cell mobilization combined with a DPP4 inhibitor leads to increased homing of bone marrow derived progenitor cells to the injured myocardium via the SDF1/CXCR4 axis resulting in improved ejection fraction and survival after acute myocardial infarction (AMI). Research design and methods After successful revascularization in AMI, 174 patients were randomized 1:1 in a multi-centre, prospective, placebo-controlled, parallel group, double blind, phase III efficacy and safety trial to treatment with G-CSF and Sitagliptin (GS) or placebo. Diabetic and non-diabetic patients were included in our trial. The primary efficacy endpoint hierarchically combined global left and right ventricular ejection fraction changes from baseline to 6 months of follow-up (ΔLVEF , ΔRVEF ), as determined by cardiac MRI. Results At follow-up ΔLVEF as well as ΔRVEF did not differ between the GS and placebo group. Patients in the placebo group had a similar risk for a major adverse cardiac event within 12 months of follow-up as compared to patients under GS. Conclusion Progenitor cell therapy comprising the use of G-CSF and Sitagliptin after successfully revascularized acute myocardial infarction fails to show a beneficial effect on cardiac function and clinical events after 12 months. (EudraCT: 2007–003,941-34; ClinicalTrials.gov : NCT00650143 , funding: Heinz-Nixdorf foundation).