MOVEMENT: Methylnaltrexone as a Method to Improve Ticagrelor Uptake in Morphine Treated STEMI Patients
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Methylnaltrexone Methylnaltrexone bromide (Relistor®). Single intravenous injection of 8 mg (0.4 ml solution) for patients weighing 38-61 kg or 12 mg (0.6 ml solution) patients weighing 62-114 kg). |
Drug: Methylnaltrexone bromide (Relistor®).
|
| Placebo Comparator: Placebo Sodium Chloride, 9mg /mL ingle intravenous injection of 0.4 mL solution for patients weighing 38-61 kg or 0.6 mL solution patients weighing 62-114 kg). |
Drug: Sodium Chloride 9mg/mL
|
Outcome Measures
Primary Outcome Measures
- High on-treatment platelet reactivity (HPR) [Two hours after the injection of either active drug or placebo]
HPR defined as platelet reactivity index (PRI) ≥50% using VASP analysis
- Number of participants with serious adverse events [Within 48 hours after drug administration]
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.
Secondary Outcome Measures
- High on-treatment platelet reactivity [One hour after the injection of either active drug or placebo]
- Difference in ticagrelor and AR-C124910XX concentrations [One and two hours after the injection of either active drug or placebo]
- Change in patient pain according to visual analog scale [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. [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. [One and two hours after the injection of either active drug or placebo]
HPR defined as platelet reactivity index (PRI) ≥50% using VASP analysis
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Karolinska University Hospital | Stockholm | Sweden | ||
| 2 | Södersjukhuset (Stockholm South General Hospital) | Stockholm | Sweden |
Sponsors and Collaborators
- Karolinska University Hospital
Investigators
- Principal Investigator: Per Tornvall, MD, PhD, Karolinska Institutet
- Principal Investigator: Ulf Jensen, MD, PhD, Karolinska Institutet
- Principal Investigator: Nawzad Saleh, MD, PhD, Karolinska Institutet
- Principal Investigator: Loghman Henareh, MD; PhD, Karolinska Institutet
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 880526