Sitagliptin Plus Granulocyte-colony Stimulating Factor in Acute Myocardial Infarction (SITAGRAMI)
Recruitment status was: Recruiting
This Phase III, investigator-driven, randomised, placebo-controlled efficacy and safety study will compare the effects of Sitagliptin in combination with granulocyte-colony stimulating factor (Lenograstim, G-CSF) on the improvement of myocardial function in patients undergoing routine percutaneous coronary revascularisation for acute myocardial infarction (time from onset of infarction to intervention 2 to 24 hours). The primary objective of this study is to compare between a treatment of G-CSF plus Sitagliptin, (G-CSF/Sitagliptin treatment group, n=87) versus Placebo (control treatment group, n=87) in change of global myocardial function from baseline to 6 months of follow-up.
|Acute Myocardial Infarction||Drug: Lenograstim (GRANOCYTE)=GCSF Drug: Sitagliptin (Januvia) Drug: Sodium Chloride (NaCl) 0.9 % Drug: Gelatin||Phase 2 Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Safety and Efficacy of Sitagliptin Plus Granulocyte-colony Stimulating Factor in Patients Suffering From Acute Myocardial Infarction|
- Change of global myocardial function from baseline to 6 months of follow-up. [ Time Frame: Recruitment period: 4,5 years. Follow-up assessment: 1 year. Analyses and reporting: 6 months. Overall duration: 6 years. ]
- Segmental end-diastolic myocardial thickness, segmental systolic wall thickening, regional contractile reserve, end-diastolic and end-systolic volumes, stroke volume, and cardiac output in MRI [ Time Frame: 6 months of follow-up ]
- Extent of non-viable myocardium will be monitored from baseline up to 6 months measured by MRI delayed enhancement. [ Time Frame: 6 months follow up ]
- Change of myocardial perfusion at rest up to 6 months as measured by signal-time curve parameters using first-pass perfusion MRI [ Time Frame: 6 month follow up ]
- Occurrence of major adverse cardiac events (death, myocardial infarction, CABG, or re-intervention) up to 12 months. [ Time Frame: 12 months follow up ]
- Safety of a treatment of Sitagliptin in combination with G-CSF in CAD patients suffering from MI (spontaneously reported adverse events (AEs) up to 12 months). [ Time Frame: 12 months follow up ]
- Change of peripheral blood stem cell populations: CD34, CD34/KDR and CD34/CD26 positive cells prior to and 5 days after therapy initiation. [ Time Frame: 1 week follow up ]
- Change of plasma levels of NT-pro-BNP, glucose, complete blood count, CRP, platelets, CK, cTnI prior to and 5 and 28 days, and 6 months after therapy initiation [ Time Frame: 12 month follow up ]
- Assessment of in stent restenosis using angiography 6 months after facultative PCI [ Time Frame: 6 month follow up ]
|Study Start Date:||March 2008|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Active Comparator: 1
Application G-CSF (10µg/kg/d divided in two doses subcutaneously) over a period of 5 days and Sitagliptin 100 mg each day for 28 days.
Drug: Lenograstim (GRANOCYTE)=GCSF
10 µg/kg/d s.c. for 5 days divided in two dosages per dayDrug: Sitagliptin (Januvia)
100 mg p.o. per day for 28 days
Placebo Comparator: 2
NaCl 0.9% applied twice daily over a period of 5 days and oral Placebo given once a day for 28 days.
Drug: Sodium Chloride (NaCl) 0.9 %
applied s.c. twice a day for 5 daysDrug: Gelatin
One capsule p.o. per day for 28 days
The trial will be conducted as a multi-centre trial. Secondary objectives of this study are to monitor changes of regional myocardial function, myocardial perfusion and extent of non-viable myocardium from baseline to 6 months after revascularisation between the treatment groups. Furthermore the following parameters over up to 12 months of follow-up are analysed: occurrence of major adverse cardiac events (death, myocardial infarction, coronary bypass grafting, or re-intervention), spontaneously reported adverse events. Analyses of cardiac function consists of evaluation of segmental systolic wall thickening, end-diastolic volume, end-systolic volume, stroke volume, ejection fraction and cardiac output by means of magnetic resonance imaging (MRI). The extent of non-viable myocardium and myocardial perfusion will be assessed using contrast enhanced MRI.
This study consists of a revascularisation period (angioplasty of the infarcted vessel), a treatment period (up to 28 days), and a follow-up period (up to 12 months). The Revascularisation Period starts with the treatment of the patient in the emergency room. As soon as possible the patient will be transferred to the catheterisation laboratory where acute percutaneous coronary intervention (PCI) of the infarct-related artery will be performed. The first phase of the Treatment Period consists of a screening period during which a patient's eligibility is preliminarily evaluated. The second phase of the Treatment Period is the randomisation for patients in the control or G-CSF/Sitagliptin treatment group. After baseline MRI, patients are randomised. Patients will be treated either with G-CSF (10µg/kg/d divided in two doses subcutaneously) over a period of 5 days and Sitagliptin 100 mg each day for 28 days or with placebo. Patients will be randomised in 1:1 ratio to the control and verum therapy treatment groups. Follow-up Period assessments will be performed in all patients at 6 months including clinical status, occurrence of adverse events, laboratory investigations, and MRI. To assess occurrence of in-stent restenosis, routine control angiography will be performed in all patients 6 months after initial PCI. Safety will be evaluated by monitoring treatment-emergent signs and symptoms, 12-lead ECGs, vital signs, physical examination, and clinical laboratory assessments after 1 month and 1 year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00650143
|Contact: Wolfgang M Franz, Prof. Dr.||++email@example.com|
|Contact: Hans D Theiss, Dr.||++firstname.lastname@example.org|
|Clinic of the University of Munich-Grosshadern, Department of Cardiology||Recruiting|
|Munich, Germany, 81377|
|Sub-Investigator: Hans D Theiss, Dr.|
|Principal Investigator:||Wolfgang M Franz, Prof. Dr.||Clinic of the University of Munich-Grosshadern, Department of Cardiology|