This study will examine the impact of the peripheral opioid antagonist methylnaltrexone on the onset of effect of ticagrelor in morphine treated patients with ST elevation myocardial infarction (STEMI). Half of the participants will receive methylnaltrexone, while the other half will receive placebo.
The rate of drug absorption in the gastro-intestinal tract is often determined by the rate of gastric emptying. Morphine treatment, which is frequently given in order to relieve pain in patients with STEMI, is known to delay gastric emptying, and has indeed emerged as a predictor of delayed/poor antiplatelet response in patients receiving oral prasugrel or ticagrelor. In recent years, morphine has been found to delay the onset of oral P2Y12-inhibitors. To counteract this, the investigators hypothesized that an opioid antagonist may be used. The opioid antagonist naloxone has previously been shown to reduce the morphine induced delay in gastric emptying However, naloxone crosses the blood-brain barrier (BBB) and reduces the pain relieving effects of morphine. In contrast, the morphine antagonist methylnaltrexone has a reduced passage over the BBB and acts primarily as a peripheral morphine antagonist without affecting the morphine-mediated central analgesic effects. The aim of the planned study is to evaluate whether methylnaltrexone bromide may reduce the morphine induced delay in onset of platelet inhibition after a loading dose of 180 mg ticagrelor in morphine treated patients with STEMI undergoing primary percutaneous coronary intervention (PCI), where a rapid and adequate platelet inhibition after the administration of ticagrelor is crucial. As morphine is an inclusion criterion, all patients included in the study will be on morphine treatment. Thus, morphine treatment is not an intervention to be administered as part of the protocol. Stratification according to inferior and anterior/lateral STEMI will be perform to avoid imbalance in the location of myocardial infarction between the groups.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
82
Karolinska University Hospital
Stockholm, Sweden
Södersjukhuset (Stockholm South General Hospital)
Stockholm, Sweden
High on-treatment platelet reactivity (HPR)
HPR defined as platelet reactivity index (PRI) ≥50% using VASP analysis
Time frame: Two hours after the injection of either active drug or placebo
Number of participants with serious adverse events
Serious AE is any untoward medical occurrence that at any dose: * Results in death. * Is life-threatening at the time of the event. * Requires inpatient hospitalization. * Requires prolongation of existing hospitalization. * Results in persistent or significant disability/incapacity. * Is a congenital anomaly/birth defect.
Time frame: Within 48 hours after drug administration
High on-treatment platelet reactivity
Time frame: One hour after the injection of either active drug or placebo
Difference in ticagrelor and AR-C124910XX concentrations
Time frame: One and two hours after the injection of either active drug or placebo
Change in patient pain according to visual analog scale
Time frame: One and two hours after the injection of either active drug or placebo
Difference in ticagrelor and AR-C124910XX concentrations between patients with inferior STEMI and patients with anterior/lateral STEMI.
Time frame: One and two hours after the injection of either active drug or placebo
Difference in high on-treatment platelet reactivity (HPR) between patients with inferior STEMI and patients with anterior/lateral STEMI.
HPR defined as platelet reactivity index (PRI) ≥50% using VASP analysis
Time frame: One and two hours after the injection of either active drug or placebo
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