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).

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).

• Authors: Christoph Brenner, Christine Adrion, Ulrich Grabmaier, Daniel Theisen, Franz von Ziegler, Alexander Leber, Alexander Becker, Hae-Young Sohn, Ellen Hoffmann, Ulrich Mansmann, Gerhard Steinbeck, Wolfgang-Michael Franz, Hans Diogenes Theiss
• Journal: International journal of cardiology (Int J Cardiol) Vol. 205 Pg. 23-30 (Feb 15 2016) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 26709136 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015. Published by Elsevier Ireland Ltd.

Chemical References

• Granulocyte Colony-Stimulating Factor
• Sitagliptin Phosphate

Topics

• Aged
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Granulocyte Colony-Stimulating Factor (administration & dosage, adverse effects)
• Humans
• Male
• Middle Aged
• Myocardial Infarction (diagnosis, epidemiology, therapy)
• Prospective Studies
• Sitagliptin Phosphate (administration & dosage, adverse effects)
• Stem Cell Transplantation (adverse effects, methods)
• Stroke Volume (drug effects, physiology)
• Treatment Outcome