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

NCT ID: NCT02942550

Last Updated: 2018-04-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2017-12-31

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.

Conditions

STEMI; Morphine; Ticagrelor; Methylnaltrexone

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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).

Group Type: ACTIVE_COMPARATOR

Methylnaltrexone bromide (Relistor®).

Intervention Type: DRUG

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).

Group Type: PLACEBO_COMPARATOR

Sodium Chloride 9mg/mL

Intervention Type: DRUG

Interventions

Methylnaltrexone bromide (Relistor®).

Intervention Type: DRUG

Sodium Chloride 9mg/mL

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karolinska University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jan van der Linden

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Per Tornvall, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Ulf Jensen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Nawzad Saleh, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Loghman Henareh, MD; PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Locations

Karolinska University Hospital

Stockholm, , Sweden

Södersjukhuset (Stockholm South General Hospital)

Stockholm, , Sweden

Countries

Sweden

References

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.

Reference Type: DERIVED

PMID: 30636504 (View on PubMed)

Other Identifiers

880526

Identifier Type: -

Identifier Source: org_study_id