Het effect van opiaten op de werking van bloedplaatjes (P2Y12 receptor remming) bij patiënten met een hartinfarct (ST-Elevation Myocardial Infarction) die vooraf worden behandeld met gemalenTicagrelor

Background of the study:

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 PD influences of fentanyl on platelet inhibition in STEMI patients who are pre-treated with crushed
ticagrelor tablets. Therefore, In the ON-TIME-3 study, we seek to show the influence of fentanyl on platelet inhibition in STEMI
patients who are pre-treated with crushed ticagrelor in the ambulance.



Objective of the study:

Primary Objective: The aim of the study is to show that STEMI patients who are pre-treated with crushed ticagrelor and
paracetamol have a higher level of platelet inhibition after primary PCI than patients pre-treated with crushed ticagrelor who are
treated with fentanyl.



Study design:

This is a multicenter, prospective, randomized, investigator-initiated open-label study



Study population:

Patients with ongoing chest pain with the diagnosis of STEMI in the ambulance.



Intervention:

Patients are randomized to paracetamol 1000mg iv or fentanyl 1-2 mcg/kg with a maximum of 4 mcg/kg iv.



Primary study parameters/outcome of the study:

The primary endpoint of the study is:

to show that patients with STEMI who are pre-treated with crushed ticagrelor 180 mg and paracetamol 1000 mg have a higher
level of platelet inhibition directly after primary PCI compared to patients pre-treated with crushed ticagrelor 180 mg and fentanyl
1-2 mcg/kg with a maximum of 4 mcg/kg.

The hypothesis is that STEMI patients who are pre-treated with crushed ticagrelor and paracetamol have a higher level of platelet inhibition after primary PCI than patients pre-treated with crushed ticagrelor who are treated with fentanyl.

Blood sample measurements for platelet function testing and level of active metabolite of ticagrelor, using Verify Now P2Y12 assay (Accumetrics, San Diego, California), will be done at four time points:

- 1: when arriving at the cathlab

- 2: directly post-primary PCI or 1 hour after
coronary angiography when no PCI was
performed

- 3: one hour post-primary PCI including
electrocardiogram (ECG) or 2 hours post- coronary angiography

- 4: six hours post-primary PCI of 7 hours
post-coronary angiography

Patients are randomized to paracetamol 1000 mg iv or fentanyl 1-2 mcg/kg with a maximum of 4 mcg/kg iv.