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

August 24, 2022 updated by: Hans Theiss, Ludwig-Maximilians - University of Munich

Safety and Efficacy of Sitagliptin Plus Granulocyte-colony Stimulating Factor in Patients Suffering From Acute Myocardial Infarction

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
174

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Munich, Germany, 81377
        • Clinic of the University of Munich-Grosshadern, Department of Cardiology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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.
Recruitment period: 4,5 years. Follow-up assessment: 1 year. Analyses and reporting: 6 months. Overall duration: 6 years.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
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
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
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
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
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
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
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
12 month follow up
Assessment of in stent restenosis using angiography 6 months after facultative PCI
Time Frame: 6 month follow up
6 month follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ludwig-Maximilians - University of Munich

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Wolfgang M Franz, Prof. Dr., Clinic of the University of Munich-Grosshadern, Department of Cardiology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2008

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 27, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 31, 2008

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 1, 2008

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 25, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 24, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 22021980

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