Impact of Morphine Treatment on Platelet Inhibition in Acute Myocardial Infarction

Study Overview
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Brief Summary
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The current prospective, randomized, controlled MonAMI trial aims to systematically examine the effects of morphine on the platelet inhibitory effects of the orally administered platelet inhibitor ticagrelor in patients with acute myocardial infarction. In addition, the potential positive or negative effects of MCP in combination with morphine on platelet inhibition will be studied.

Official Title
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Impact of Morphine Treatment on Platelet Inhibition in Acute Myocardial Infarction

Conditions
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Acute Myocardial Infarction

Intervention / Treatment
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* Drug: Morphinhydrochloricum
* Drug: Metoclopramide
* Drug: Ticagrelor
* Drug: Isotonic sodium chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ST-elevation myocardial infarction < 24 h after symptom onset or non-ST-elevation myocardial infarction with persistent chest pain < 24 h after symptom onset Intended revascularization by primary percutaneous coronary intervention Informed consent Age ≥18 years Exclusion Criteria: Age <18 years Active bleeding or bleeding diathesis Oral anticoagulation Current treatment with clopidogrel/prasugrel/ticagrelor/glycoprotein-IIb-IIIa-receptor-antagonists Current treatment with morphine and/or MCP <12 h Contraindication for treatment with platelet inhibitors Fibrinolysis <48 h Percutaneous coronary intervention or coronary artery bypass grafting <3 months Known glomerular filtration rate <30 ml/min Severe liver dysfunction Hypersensitivity to ticagrelor or any excipients History of intracranial hemorrhage Known pregnancy, breast-feeding or intend to become pregnant during the study period Participation in other trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Isotonic sodium chloride + Ticagrelor<br>46 patients with NaCl i.v. and 180 mg ticagrelor orally pre revascularization plus medical standard therapy | Drug: Ticagrelor<br>* 180 mg ticagrelor orally<br>* Other names: Brilique (manufacturer: AstraZeneca);Drug: Isotonic sodium chloride<br>* 10 ml NaCl 0.9% intravenously<br>* Other names: NaCl (manufacturer: Berlin-Chemie Menarini);|
| Experimental: Morphinhydrochloricum + Ticagrelor<br>46 patients with 5 mg morphine i.v. and 180 mg ticagrelor pre revascularization plus medical standard therapy | Drug: Morphinhydrochloricum<br>* 5 mg morphine intravenously<br>* Other names: Morphin-hameln (manufacturer: hameln pharmaceuticals);Drug: Ticagrelor<br>* 180 mg ticagrelor orally<br>* Other names: Brilique (manufacturer: AstraZeneca);|
| Experimental: Morphinhydrochloricum + Ticagrelor + Metoclopramide<br>46 patients with 5 mg morphine i.v. and 10 mg MCP i.v. and 180 mg ticagrelor pre revascularization plus medical standard therapy | Drug: Morphinhydrochloricum<br>* 5 mg morphine intravenously<br>* Other names: Morphin-hameln (manufacturer: hameln pharmaceuticals);Drug: Metoclopramide<br>* 10 mg MCP intravenously<br>* Other names: MCP-ratiopharm (manufacturer: Ratiopharm);Drug: Ticagrelor<br>* 180 mg ticagrelor orally<br>* Other names: Brilique (manufacturer: AstraZeneca);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet activity 2 hours after administration of loading dose of ticagrelor measured by VerifyNow-P2Y12-test |  | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet reactivity 0.5, 1, 4, 6 and 24 hours after loading dose of ticagrelor measured by VerifyNow-P2Y12-test |  | 0.5, 1, 4, 6 h and 24 hours | 
| Platelet reactivity 0.5, 1, 2, 4, 6 and 24 hours after loading dose of ticagrelor measured by Vasodilator Stimulated Phosphoprotein-test |  | 0.5, 1, 2, 4, 6 h and 24 hours | 
| Percentage of patients with high on-treatment platelet reactivity 0.5, 1, 2, 4, 6 and 24 hours after loading dose of ticagrelor (measured by VerifyNow-P2Y12-test) |  | 0.5, 1, 2, 4, 6 h and 24 hours | 
| Ticagrelor plasma levels and levels of active serum metabolites after 0.5, 1, 2, 4, 6 and 24 hours |  | 0.5, 1, 2, 4, 6 h and 24 hours | 
| Infarct size measured by delayed enhancement magnetic resonance imaging |  | Day 1-4 | 
| Microvascular obstruction measured by delayed enhancement magnetic resonance imaging | Cardiac magnetic resonance imaging equivalent of angiographic no-reflow, expressed as percentage of left ventricular mass | Day 1-4 |