The Effect of Opioids on P2Y12 Receptor Inhibition in Patients With ST-Elevation Myocardial Infarction Who Are Pre-treated With Crushed Ticagrelor

Study Overview
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Brief Summary
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Fast and accurate platelet inhibition is an important therapeutic goal in the acute treatment of patients with ST-segment elevation myocardial infarction (STEMI). Platelet inhibitory effects induced by normal oral P2Y12 receptor antagonists, for example ticagrelor, are delayed in STEMI patients undergoing primary percutaneous coronary intervention (primary PCI), which may be attributed to impaired absorption affecting drug pharmacokinetics (PK) and pharmacodynamics (PD). Another therapeutic goal in the acute treatment of STEMI is reduction of sympathetic stress and catecholamine release, thereby improving the balance between the demand for and supply of oxygen, by analgesia like fentanyl of morphine. To date, there are no studies that have specifically assessed the pharmacodynamics influences of fentanyl on platelet inhibition in STEMI patients who are pre-treated with crushed ticagrelor tablets. Therefore, In the ON-TIME-3 study, the investigators seek to show the influence of fentanyl on platelet inhibition in STEMI patients who are pre-treated with crushed ticagrelor in the ambulance.

Official Title
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The Effect of Opioids on P2Y12 Receptor Inhibition in Patients With ST-Elevation Myocardial Infarction Who Are Pre-treated With Crushed Ticagrelor

Conditions
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STEMI, STEMI - ST Elevation Myocardial Infarction

Intervention / Treatment
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* Drug: Paracetamol
* Drug: Fentanyl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: i. age ≥18 years ii. referred by ambulance paramedics to Isala (Zwolle) or Zuyderland Hospital (Heerlen) iii. diagnosed in the ambulance with STEMI defined as: ongoing chest pain >30 minutes and <12 hours duration and ST-segment elevation >0.1 milliVolt in at least 2 contiguous leads iv. ongoing chest pain with a pain score (NRS) ≥4 v. the patient has been informed of the nature of the study, agrees to its provisions and has provided verbal informed consent in the pre-hospital phase followed by written informed consent in hospital Exclusion Criteria: i. presenting with cardiogenic shock; defined as: systolic blood pressure <90 mmHg and heart rate >100/min and peripheral oxygen saturation <90% (without oxygen administration) ii. patients with a nasogastric tube in situ or requiring a nasogastric tube iii. patients who already received fentanyl or paracetamol <2 hours prior to randomization iv. patients on current treatment with P2Y12 inhibitors (ticagrelor, clopidogrel or prasugrel) v. allergy to morphine or paracetamol vi. patients with recent major bleeding complications or contraindication to dual antiplatelet therapy: hypersensitivity to aspirin or ticagrelor current use of (new) oral anticoagulation history of bleeding diathesis or known coagulopathy active bleeding refusal of blood transfusions history of intracerebral mass, aneurysm, arteriovenous malformation, or hemorrhagic stroke known severe liver dysfunction vii. received any organ transplant or is on a waiting list for any organ transplant viii. patients undergoing dialysis ix. pregnant or lactating female x. patients currently participating in another investigational drug or device study

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
Interventional Model Description: randomized controlled trial, with randomization to either paracetamol intravenously or fentanyl.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: paracetamol<br>Patients are randomized to paracetamol 1000 mg iv or fentanyl 1-2 mcg/kg with a maximum of 4 mcg/kg iv. | Drug: Paracetamol<br>* Patients are randomized to paracetamol 1000 mg iv or fentanyl 1-2 mcg/kg with a maximum of 4 mcg/kg iv.<br>|
| Active Comparator: fentanyl<br> | Drug: Fentanyl<br>* Patients are randomized to paracetamol 1000 mg iv or fentanyl 1-2 mcg/kg with a maximum of 4 mcg/kg iv.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| platelet reactivity | Platelet reactivity units (PRU) directly post-PCI or 1 hour post-angiography | directly post-PCI or 1 hour post-angiography |