Intracoronary Darbepoetin-alpha to Reduce The Infarct Size and Post-Infarct Remodeling

Seoul National University

Status and phase: Completed; Phase 2

Conditions: Myocardial Infarction

Treatments: Drug: Darbepoetin alfa; Drug: Control Saline

Study type: Interventional

Funder types: Other

Identifiers

NCT01538771

DAMI

Details and patient eligibility

About

Prospective, randomized and open label trial

Hypothesis

• Infusion of intracoronary darbepoetin-alpha at the time of reperfusion may reduce infarct size and post-infarct pathologic left ventricular remodeling in patients with ST-segment elevation myocardial infarction.

Methods

• Randomization into control group or treatment group
• Treatment group : Darbepoetin-alpha 300ug intracoronary bolus infusion via over-the-wire balloon system simultaneously with first balloon inflation and conventional treatment
• Control group : conventional treatment

Endpoints

• peak CK-MB & troponin levels : baseline,6h,12hr,18hr, 24hr, 36hr and 48hr
• MRI at baseline : infarct size, area at risk and salvaged myocardium
• MRI at 4 months : prevalence of pathologic left ventricle remodeling (definition: increase of end-diastolic volume index > 20% compared to baseline)
• safety endpoint : cardiac death, nonfatal myocardial infarction, stent thrombosis, ischemic stroke, hospital readmission with heart failure or ischemic symptom, bleeding and urgent target lesion revascularization

Full description

[Eligibility Criteria]

1. Patients, regardless of gender, at the age from 18 to 80 years were eligible if they had within 12 hours of onset of ST-segment myocardial infarction that was decided to treat with primary percutaneous coronary intervention.

[Exclusion criteria]

1. Uncontrolled congestive heart failure (Killip classes II and III, or cardiogenic shock)
2. History of malignancy
3. Serious hematological disease
4. Current infectious disease requiring antibiotic therapy
5. Baseline creatinine level > 2.0 mg/dL or dependence on dialysis
6. Known hypersensitivity to or contraindication for heparin, aspirin, clopidogrel, sirolimus, everolimus, contrast medium and darbepoetin-α

[Primary endpoint] Myocardial infarct size, estimated by measurement of peak levels of cardiac biomarker (CK-MB and troponin-I of the patients was followed for 48 hours at every 6 hours)

[Secondary end points]

1. The infarct size, measured as the area of delayed enhancement seen with cardiac magnetic resonance (CMR) imaging on average four days after ST-segment elevation myocardial infarction (baseline)
2. The proportion of area at risk (AAR) and salvaged myocardium, calculated by formula; [AAR - Infarct size] / AAR X 100 (%)
3. The change of left ventricular ejection fraction (LVEF), LV end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV) assessed by CMR between four days and four months
4. LV remodeling index [(LVEDV at four months - baseline LVEDV) / baseline LVEDV X 100%] and the incidence of pathologic LV remodeling (LV remodeling index > 20%);

[Safety endpoints] The incidence of composites of the cardiovascular endpoints (cardiac death, nonfatal myocardial infarction, stent thrombosis, ischemic stroke, hospital readmission with heart failure or ischemic symptoms, bleeding and urgent target lesion revascularization) assessed at four months.

Enrollment: 80 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with ST-elevation myocardial infarction (MI) within 12 hours of onset
• Suitable coronary anatomy for PCI
• Age < 80 yrs

Exclusion criteria

• Uncontrolled congestive heart failure (Killip classes II and III, or cardiogenic shock)
• History of malignancy
• Serious hematological disease
• Current infectious disease requiring antibiotic therapy
• Baseline creatinine level > 2.0 mg/dL or dependence on dialysis
• Known hypersensitivity to or contraindication for heparin, aspirin, clopidogrel, sirolimus, everolimus, contrast medium and darbepoetin-α

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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80 participants in 2 patient groups, including a placebo group

Control group

Placebo Comparator group

Description:

Received same volume of saline

Treatment:

Drug: Control Saline

Darbepoetin group

Active Comparator group

Description:

Darbepoetin alfa 300ug intracoronary bolus infusion via over-the-wire balloon before the 1st ballooning \& conventional treatment

Treatment:

Drug: Darbepoetin alfa