Safety and efficacy of SITAgliptin plus GRanulocyte-colony-stimulating factor in patients suffering from Acute Myocardial Infarction (SITAGRAMI-Trial)--rationale, design and first interim analysis.
OBJECTIVE
Our pre-clinical studies demonstrated that G-CSF based stem cell mobilization in combination with genetic or pharmaceutical CD26/DPP-IV inhibition after acute myocardial infarction leads to improved cardiac homing of stem cells, enhanced heart function and increased survival. Thereupon, we initiated a phase III, multi-centre, randomised, placebo-controlled efficacy and safety study (n=100) analyzing the effect of combined application of G-CSF and Sitagliptin, which is a clinically admitted, anti-diabetic DPP-IV-inhibitor, after acute myocardial infarction ("SITAGRAMI-Trial"; EudraCT Number: 2007-003941-34).


METHODS
The primary objective of the study is to assess myocardial regeneration by improved myocardial homing of mobilized stem cells, as measured by cardiac function using MRI analysis. In this paper, we report on the study design and a planned first interim-analysis on safety issues without unblinding.


RESULTS
During the first 6 weeks of follow-up, only two major adverse cardiac events occurred (one de novo stenosis and one instent-restenosis) in the first 36 patients. Presumably, they were not related to any study medication. No other side effects like headache, bone pain, hypoglycaemias etc. were observed. Furthermore, no myocardial infarction or death occurred in any patient. Thus, the rate of serious adverse events lay within the expected range.


CONCLUSIONS
Our data demonstrate that the combined application of Sitagliptin and G-CSF seems to be safe on the short term and feasible after acute myocardial infarction and may represent a new therapeutic option in future.
Theiss
Hans D
HD
Medical Department I - Cardiology, Germany.
Brenner
Christoph
C
Medical Department I - Cardiology, Germany.
Engelmann
Markus G
MG
Medical Department I - Cardiology, Germany.
Zaruba
Marc-Michael
MM
Medical Department I - Cardiology, Germany.
Huber
Bruno
B
Medical Department I - Cardiology, Germany.
Henschel
Volkmar
V
Institute for medical Informatics, Biometry und Epidemiology, Germany.
Mansmann
Ulrich
U
Institute for medical Informatics, Biometry und Epidemiology, Germany.
Wintersperger
Bernd
B
Institute of Radiology, all Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Reiser
Maximilian
M
Institute of Radiology, all Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Steinbeck
Gerhard
G
Medical Department I - Cardiology, Germany.
Franz
Wolfgang-M
WM
Medical Department I - Cardiology, Germany. Electronic address: wolfgang.franz@med.uni-muenchen.de.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects*; D000068900:Sitagliptin Phosphate; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects*
D011719:Pyrazines; D014230:Triazoles; D016179:Granulocyte Colony-Stimulating Factor; D000068900:Sitagliptin Phosphate