Sitagliptin Plus Granulocyte-colony Stimulating Factor in Acute Myocardial Infarction (SITAGRAMI)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2011 by Ludwig-Maximilians - University of Munich.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
HEINZ NIXDORF-FOUNDATION
Information provided by:
Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier:
NCT00650143
First received: March 27, 2008
Last updated: July 7, 2011
Last verified: July 2011
  Purpose

Trial design:

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.


Condition Intervention Phase
Acute Myocardial Infarction
Drug: Lenograstim (GRANOCYTE)=GCSF
Drug: Sitagliptin (Januvia)
Drug: Sodium Chloride (NaCl) 0.9 %
Drug: Gelatin
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Ludwig-Maximilians - University of Munich:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Occurrence of major adverse cardiac events (death, myocardial infarction, CABG, or re-intervention) up to 12 months. [ Time Frame: 12 months follow up ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Assessment of in stent restenosis using angiography 6 months after facultative PCI [ Time Frame: 6 month follow up ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 174
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)
Arms Assigned Interventions
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.

n=74

Drug: Lenograstim (GRANOCYTE)=GCSF
10 µg/kg/d s.c. for 5 days divided in two dosages per day
Drug: 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.

n=74

Drug: Sodium Chloride (NaCl) 0.9 %
applied s.c. twice a day for 5 days
Drug: Gelatin
One capsule p.o. per day for 28 days

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  1. Be at least 18 years old, male or female
  2. Have acute ST segment elevation myocardial infarction (typical chest pain of more than 30 minutes duration, presence of ST-segment elevation in at least two contiguous leads or left bundle-branch block) and/or occluded coronary artery
  3. Intervention of infarct related artery by PCI/Stenting within 2-24 hours after onset of acute myocardial infarction.
  4. have creatinin kinase elevation of more than three times of upper normal level (i.e. 540 U/l) accompanied by a significant elevation of CK-MB isoenzyme and/or Troponin I/T
  5. Have regional wall motion abnormality (comprising hypo-, a- or dyskinesia) of at least one myocardial segment demonstrated with MRI.
  6. Patients who are further suitable for coronary angiography and angioplasty with stenting of the infarct related artery.
  7. Have the ability to understand the requirements of the study, and agree and be able to return for the required assessments.
  8. Give a written informed consent.

Exclusion criteria

General:

  1. Women of childbearing potential, pregnancy or being lactating.
  2. Be unable to undergo percutaneous cardiac catheterisation
  3. Have contraindications against magnetic resonance imaging (e.g. non-MR compatible implants or medical devices)
  4. Have conditions that may severely degrade image quality (e.g. severe arrhythmia) or prevents from MR scanning (e.g. claustrophobia)
  5. Previous enrolment in the present trial or administration of any study medication within the previous 30 days. Study drug is defined as any material (placebo or drug) dispensed under the provisions of a protocol.
  6. Have other severe concurrent illness (e.g., active infection, malignancy).
  7. Life expectancy of less than one year.
  8. Have a history of alcohol or drug abuse within 3 months prior to admission or factors jeopardising follow-up.

Renal, hepatic, metabolic:

  1. Moderate to severe renal impairment (Crea level >1.7 mg/dL or glomerular filtration rate <35 ml/min).
  2. Diabetes type 1 patients.
  3. Diabetic ketoacidosis.
  4. Concomitant medications known to cause hypoglycemia, such as sulfonylureas.
  5. Severe liver dysfunction.

Haematologic:

  1. Malignant haematological diseases, i.e. chronic myeloic leukemia (CML) or myelodysplastic syndromes (MDS)
  2. Severe congenital neutropenia with cytogenetic abnormalities
  3. Known allergic reaction vs. Lenograstim

Cardiovascular:

  1. Acute cardiogenic shock
  2. Cardiomyopathy with an ejection fraction below 0.25 (i.e. ischemic or dilated cardiomyopathy resulting in congestive heart failure)
  3. Infective endocarditis
  4. Factors contraindicating cardiac catheterisation (e.g. severe allergy against iodine, severe thyroid disease)
  5. Planned operative revascularisation
  6. Left ventricular thrombus
  7. Severe cardiac arrhythmias (i.e. malignant sustained or non-sustained ventricular tachycardia or ventricular fibrillation) within 24 hours after admission.

Pulmonary:

  1. Acute massive pulmonary infiltrations
  2. History of pneumonia in the last 4 weeks

Other:

1. Therapy with immunosuppressants, cytostatics, corticoids.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00650143

Contacts
Contact: Wolfgang M Franz, Prof. Dr. ++49-89-7095-6095 wolfgang.franz@med.uni-muenchen.de
Contact: Hans D Theiss, Dr. ++49-89-7095-3074 hans.theiss@med.uni-muenchen.de

Locations
Germany
Clinic of the University of Munich-Grosshadern, Department of Cardiology Recruiting
Munich, Germany, 81377
Sub-Investigator: Hans D Theiss, Dr.         
Sponsors and Collaborators
Ludwig-Maximilians - University of Munich
HEINZ NIXDORF-FOUNDATION
Investigators
Principal Investigator: Wolfgang M Franz, Prof. Dr. Clinic of the University of Munich-Grosshadern, Department of Cardiology
  More Information

Publications:
Responsible Party: Principal Investigator: Prof. Dr. Wolfgang-Michael Franz, Clinic of the University of Munich - Grosshadern, Department of Cardiology
ClinicalTrials.gov Identifier: NCT00650143     History of Changes
Other Study ID Numbers: 22021980
Study First Received: March 27, 2008
Last Updated: July 7, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Germany: Ethics Commission

Keywords provided by Ludwig-Maximilians - University of Munich:
Stem cell
Myocardial infarction
G-CSF
CD26-inhibition

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Lenograstim
Sitagliptin
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents

ClinicalTrials.gov processed this record on July 24, 2014