Mangafodipir as an Adjunct to Percutaneous Coronary Intervention

Study Overview
=================
Brief Summary
-----------------
The present feasibility study is designed to find out whether pre-treatment with the compound mangafodipir (PP-099) provides an additional reduction in myocardial infarct size in patients treated with primary percutaneous coronary intervention (PCI) during acute myocardial infarction (AMI).

Detailed Description
-----------------
Mangafodipir, manganese (Mn) dipyridoxyl diphosphate (MnDPDP) and its lipophile metabolite Mn dipyridoxyl diethylene diamide (MnPLED), are catalytic antioxidants and iron chelators. In preclinical studies these agents reduce oxidative stress induced injuries related to chemotherapy of cancer and to reperfusion/reoxygenation of ischemic/hypoxic myocardium. Accordingly, in an in vivo pig model of AMI metabolite MnPLED applied at end of ischemia and during reperfusion reduced myocardial infarct size by 55 %. Mangafodipir most likely activates salvage pathways and prevents lethal reperfusion injuries. Other advantages are that mangafodipir is already approved as a contrast agent for MRI of liver, and that the experience for more than a decade reveals a high safety with minor and tolerable side-effects. The present study will include 20 patients treated for their first documented AMI. They will after admission to hospital undergo primary PCI. Reopening of an occluded coronary artery will be preceded by iv. infusion of mangafodipir or placebo in two groups , each consisting of 10 patients. The primary endpoint will be release to plasma of commonly accepted biomarkers of myocardial injury (Troponin T and CK-MB) measured at admission and 6 hours after PCI. The secondary endpoints include the accumulated release of plasma biomarkers over 48 hours and direct measurement of the final myocardial infarct size at 6-10 weeks after PCI.

Official Title
-----------------
Mangafodipir as an Adjunct to Percutaneous Coronary Intervention in Acute Myocardial Infarction (MANAMI)

Conditions
-----------------
Myocardial Infarction

Intervention / Treatment
-----------------
* Drug: Mangafodipir
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males 40-80 and females 50-80 years with first severe coronary attack Chest pain up to 6 hours. T segment elevation (≥ 0.2 mV in two neighbouring anterior and inferior wall leads. Decided for treatment by primary PCI. TIMI grade 0 flow in the occluded LAD or RCA artery Written informed consent. Exclusion Criteria: Previous coronary artery bypass operation. Previous AMI. Chest pain more than 6 hours. Angina within 48 hours before admission. Cardiac arrest and cardiogenic shock. Occlusion of the left main stem, circumflex and right coronary arteries at angiography. Known hypersensitivity to mangafodipir (as contrast agent for MRI). Received mangafodipir ≤ 5 weeks before admission History of prior serious allergic or pseudo-allergic reaction Severely reduced liver or renal function Any other serious illness or medical condition Fertile females Phaeochromocytoma

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Mangafodipir treatment<br>Treatment will be undertaken with a ready-to use investigative drug formulation identical to what is in diagnostic use as a contrast medium for MRI. Formulation content: MnDPDP 10 mmol/ml. | Drug: Mangafodipir<br>* Administered dose: 2 µmol/kg b.w. Administration form: Ready-to-use formulation (solution). Mangafodipir or placebo (0.2 ml/kg b.w.) will be administered as an intravenous (iv.) infusion over 2-5 min prior to reopening of occluded coronary artery during PCI<br>* Other names: Teslascan;|
| Placebo Comparator: NaCl 0.9%<br> | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of myocardial infarct size assessed by biomarker release to plasma |  | Before and at 2 days after PCI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of myocardial infarct size assessed by biomarker release to plasma and by magnetic resonance imaging (MRI) of the heart. |  | Accumulated biomarker release over 48 hours after PCI; MRI at 6-10 weeks after PCI. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Mangafodipir, Primary Percutaneous Coronary Intervention, Myocardial infarction, Troponin, CK-MB, Magnetic Resonance Imaging