Methylnaltrexone as a Method to Improve Ticagrelor Uptake in Morphine Treated STEMI Patients

STEMI Clinical Trial

— MOVEMENT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02942550
• Other study ID #: 880526
• Status: Completed
• Phase: Phase 4
• First received: September 21, 2016
• Last updated: April 5, 2018
• Start date: November 2016
• Est. completion date: December 2017

Study information

• Verified date: April 2018
• Source: Karolinska University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Methylnaltrexone
• Morphine
• ST Elevation Myocardial Infarction
• STEMI
• Ticagrelor

Intervention

Drug:
• Methylnaltrexone bromide (Relistor®).

• Sodium Chloride 9mg/mL

Locations

Country	Name	City	State
Sweden	Karolinska University Hospital	Stockholm
Sweden	Södersjukhuset (Stockholm South General Hospital)	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Karolinska University Hospital

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	High on-treatment platelet reactivity (HPR)	HPR defined as platelet reactivity index (PRI) =50% using VASP analysis	Two hours after the injection of either active drug or placebo
Primary	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.	Within 48 hours after drug administration
Secondary	High on-treatment platelet reactivity		One hour after the injection of either active drug or placebo
Secondary	Difference in ticagrelor and AR-C124910XX concentrations		One and two hours after the injection of either active drug or placebo
Secondary	Change in patient pain according to visual analog scale		One and two hours after the injection of either active drug or placebo
Secondary	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
Secondary	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	One and two hours after the injection of either active drug or placebo