Clinical trial NCT02942550: Methylnaltrexone as a Method to Improve Ticagrelor Uptake in Morphine Treated STEMI Patients
Official title: Methylnaltrexone as a Method to imprOVE Platelet Inhibition of Ticagrelor in Morphine-treated Patients With ST-segMENT Elevation Myocardial Infarction: a Prospective, Single Blinded Randomized, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: STEMI
Morphine
Ticagrelor
Methylnaltrexone
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
First posted: 2016-10-24
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of STEMI
* Administration of a 180 mg loading dose ticagrelor
* Analgesic treatment with intravenous morphine pre-PCI

Exclusion Criteria:

* Cardiac arrest
* Body weight \> 114kg
* Vomiting after intake of ticagrelor loading dose
* Use of Naloxone before inclusion or during sampling period
* Inability to understand study outline and instructions
* Methylnaltrexone bromide contraindication
* Age \<18 years; 8) Women in fertile age
* Administration of ticagrelor during the week before inclusion
* Treatment with Cangrexal
* Ongoing long-term opioid treatment.

Primary outcomes:
measure: High on-treatment platelet reactivity (HPR)
timeFrame: Two hours after the injection of either active drug or placebo
measure: Number of participants with serious adverse events
timeFrame: Within 48 hours after drug administration
Secondary outcomes:
measure: High on-treatment platelet reactivity
timeFrame: One hour after the injection of either active drug or placebo
measure: Difference in ticagrelor and AR-C124910XX concentrations
timeFrame: One and two hours after the injection of either active drug or placebo
measure: Change in patient pain according to visual analog scale
timeFrame: One and two hours after the injection of either active drug or placebo
measure: Difference in ticagrelor and AR-C124910XX concentrations between patients with inferior STEMI and patients with anterior/lateral STEMI.
timeFrame: One and two hours after the injection of either active drug or placebo
measure: Difference in high on-treatment platelet reactivity (HPR) between patients with inferior STEMI and patients with anterior/lateral STEMI.
timeFrame: One and two hours after the injection of either active drug or placebo
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Stockholm
country: Sweden
facility: Södersjukhuset (Stockholm South General Hospital)
Study officials:
affiliation: Karolinska Institutet
name: Per Tornvall, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institutet
name: Ulf Jensen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institutet
name: Nawzad Saleh, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institutet
name: Loghman Henareh, MD; PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Holm M, Tornvall P, Henareh L, Jensen U, Golster N, Alstrom P, Santos-Pardo I, Witt N, Fedchenko N, Venetsanos D, Beck O, van der Linden J. The MOVEMENT Trial. J Am Heart Assoc. 2019 Jan 22;8(2):e010152. doi: 10.1161/JAHA.118.010152.