Sitagliptin Plus Granulocyte-colony Stimulating Factor in Acute Myocardial Infarction

NCT00650143 | Completed Phase 2 DMC

• 1 other identifier: 22021980
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Myocardial Infarction

Keywords

Stem cell; Myocardial infarction; G-CSF; CD26-inhibition

Outcome Measures

Primary Outcomes (1)

• Change of global myocardial function from baseline to 6 months of follow-up.

  Recruitment period: 4,5 years. Follow-up assessment: 1 year. Analyses and reporting: 6 months. Overall duration: 6 years.

Secondary Outcomes (8)

• 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

  6 months of follow-up

• Extent of non-viable myocardium will be monitored from baseline up to 6 months measured by MRI delayed enhancement.

  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

  6 month follow up

• Occurrence of major adverse cardiac events (death, myocardial infarction, CABG, or re-intervention) up to 12 months.

  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).

  12 months follow up

Study Arms (2)

1

ACTIVE COMPARATOR

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; Drug: Sitagliptin (Januvia)

2

PLACEBO COMPARATOR

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 %; Drug: Gelatin

Interventions

Lenograstim (GRANOCYTE)=GCSF DRUG

10 µg/kg/d s.c. for 5 days divided in two dosages per day

1

Sitagliptin (Januvia) DRUG

100 mg p.o. per day for 28 days

1

Sodium Chloride (NaCl) 0.9 % DRUG

applied s.c. twice a day for 5 days

2

Gelatin DRUG

One capsule p.o. per day for 28 days

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be at least 18 years old, male or female
• 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
• Intervention of infarct related artery by PCI/Stenting within 2-24 hours after onset of acute myocardial infarction.
• 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
• Have regional wall motion abnormality (comprising hypo-, a- or dyskinesia) of at least one myocardial segment demonstrated with MRI.
• Patients who are further suitable for coronary angiography and angioplasty with stenting of the infarct related artery.
• Have the ability to understand the requirements of the study, and agree and be able to return for the required assessments.
• Give a written informed consent.

You may not qualify if:

• General:
• Women of childbearing potential, pregnancy or being lactating.
• Be unable to undergo percutaneous cardiac catheterisation
• Have contraindications against magnetic resonance imaging (e.g. non-MR compatible implants or medical devices)
• Have conditions that may severely degrade image quality (e.g. severe arrhythmia) or prevents from MR scanning (e.g. claustrophobia)
• 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.
• Have other severe concurrent illness (e.g., active infection, malignancy).
• Life expectancy of less than one year.
• Have a history of alcohol or drug abuse within 3 months prior to admission or factors jeopardising follow-up.
• Renal, hepatic, metabolic:
• Moderate to severe renal impairment (Crea level \>1.7 mg/dL or glomerular filtration rate \<35 ml/min).
• Diabetes type 1 patients.
• Diabetic ketoacidosis.
• Concomitant medications known to cause hypoglycemia, such as sulfonylureas.
• Severe liver dysfunction.

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead

Study Sites (1)

Clinic of the University of Munich-Grosshadern, Department of Cardiology

Munich, 81377, Germany

Location

Related Publications (2)

• Engelmann MG, Theiss HD, Hennig-Theiss C, Huber A, Wintersperger BJ, Werle-Ruedinger AE, Schoenberg SO, Steinbeck G, Franz WM. Autologous bone marrow stem cell mobilization induced by granulocyte colony-stimulating factor after subacute ST-segment elevation myocardial infarction undergoing late revascularization: final results from the G-CSF-STEMI (Granulocyte Colony-Stimulating Factor ST-Segment Elevation Myocardial Infarction) trial. J Am Coll Cardiol. 2006 Oct 17;48(8):1712-21. doi: 10.1016/j.jacc.2006.07.044. Epub 2006 Sep 11.

  PMID: 17045910 BACKGROUND

• Brenner C, Adrion C, Grabmaier U, Theisen D, von Ziegler F, Leber A, Becker A, Sohn HY, Hoffmann E, Mansmann U, Steinbeck G, Franz WM, Theiss HD. 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). Int J Cardiol. 2016 Feb 15;205:23-30. doi: 10.1016/j.ijcard.2015.11.180. Epub 2015 Nov 30.

  PMID: 26709136 DERIVED

MeSH Terms

Conditions

Myocardial Infarction

Interventions

Lenograstim; Sitagliptin Phosphate; Sodium Chloride; Gelatin

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Scleroproteins

Study Officials

• Wolfgang M Franz, Prof. Dr.

  Clinic of the University of Munich-Grosshadern, Department of Cardiology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 27, 2008
• First Posted: April 1, 2008
• Study Start: March 1, 2008
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2013
• Last Updated: August 25, 2022

Record last verified: 2022-08

Locations

DE (1)