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ANalgesic Efficacy and Safety of MOrphiNe Versus Methoxyflurane in Patients With Acute Myocardial Infarction

Phase 3
Recruiting
Conditions
ST Elevation Myocardial Infarction
Non ST Segment Elevation Acute Coronary Syndrome
Interventions
Registration Number
NCT04476173
Lead Sponsor
Collegium Medicum w Bydgoszczy
Brief Summary

The purpose of this study is to evaluate analgesic efficacy of inhaled methoxyflurane vs intravenous morphine in patients presenting with acute ST-elevation (STEMI) / non ST-elevation acute coronary syndrome (NSTE-ACS)

Detailed Description

Platelet activation plays a pivotal role in the pathophysiology of acute coronary syndromes (ACS). Pharmacological platelet inhibition with P2Y12 receptor antagonists and aspirin, together with percutaneous coronary intervention (PCI) are the cornerstone of treatment of ACS patients.

Chest pain and anxiety are both associated with sympathetic activation, which increases workload of the heart. Relieving of these symptoms in acute myocardial infarction (AMI) is expected to improve the balance between the demand for oxygen and its supply. Morphine, apart from its analgesic effects, also alleviates the work of breathing and reduces anxiety. However, despite its favourable analgesic and sedative actions, morphine also exerts adverse effects, which include vomiting and reduction of gastrointestinal motility. These side effects affect the intestinal absorption of oral drugs co-administered with morphine. Previously performed randomized studies revealed unfavourable influence of morphine on the pharmacokinetics of ticagrelor resulting in weaker and retarded antiplatelet effect.

Methoxyflurane was shown to be effective and well tolerated for the management of acute traumatic pain with a rapid onset of analgesia. As it does not affect the μ-opioid receptors, which inhibit propulsive motility and secretion of the gastro-intestinal tract, methoxyflurane is not expected to decrease or delay absorption or effects of orally administered drugs, including P2Y12 inhibitors, as well as to exert any other negative impact in patients with ACS.

Before PCI for the index ACS, after obtaining informed consent patients will be enrolled and randomly assigned with a secure on-line system in 1:1 ratio to one of two study arms. Patients in the intervention arm will receive methoxyphlurane administered by inhalation, whereas patients in the control arm will obtain morphine administered intravenously.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
200
Inclusion Criteria
  • diagnosis of ST-elevation myocardial infarction (STEMI) or non-ST-elevation acute coronary syndrome (NSTE-ACS)
  • patients aged from 18 to 80 years
Exclusion Criteria
  • pregnancy
  • manifest infection or inflammatory state
  • cardiogenic shock during screening for eligibility
  • respiratory failure
  • heart failure (NYHA class III or IV during screening for eligibility)
  • uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >100 mmHg)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MethoxyfluraneMethoxyflurane - PenthroxPatients treated with inhaled methoxyflurane (3 mg)
MorphineMorphinePatients treated with intravenous morphine (5 mg)
Primary Outcome Measures
NameTimeMethod
Measure of pain intensity according to the Numeric Pain Rating Scale (NPRS) 2-3 minutes after drug administration in relation to pain intensity assessed before drug administration2-3 mins

NPRS score before and 2-3 minutes after drug administration in each study arm

Measure of pain intensity according to the Numeric Pain Rating Scale (NPRS) immediately after PCI in relation to pain intensity assessed before drug administrationimmediately after PCI

NPRS score before drug administration and and immediately after PCI in each study arm

Secondary Outcome Measures
NameTimeMethod
Adverse effects of evaluated therapies24 hours

nausea, vomiting, dry mouth, respiratory failure - need for intubation, headache, dizziness, drowsiness, loss of consciousness, death

Need for GPIIb/IIIa (glycoprotein IIb/IIIa) inhibitor administration during PCI due to large intracoronary thrombus24 hours

The percentage of patients who required GP IIb/IIIa administration in each study arm

Angiographic effect of PCI using Thrombolysis In Myocardial Infarction (TIMI) scalethrough study completion, an average of 1 year

central analysis of coronary angiography after PCI according to Thrombolysis In Myocardial Infarction (TIMI) scale (TIMI 0 to TIMI 3; where TIMI 0 corresponds with no antegrade flow beyond the point of occlusion whereas TIMI 3 - normal flow with complete filling of the distal territory)

Angiographic effect of PCI using TIMI Myocardial Perfusion Grade (TMPG) scalethrough study completion, an average of 1 year

central analysis of coronary angiography after PCI according to TIMI Myocardial Perfusion Grade (TMPG) scale (TMPG 0 to TMPG 3, where TMPG 0 corresponds with failure of dye to enter the microvasculature, indicating a lack of tissue level perfusion whereas TMPG 3 - normal entry and exit of dye from the microvasculature)

ST elevation resolution in STEMI patients after PCI1 hour after PCI

central analysis of ST elevation reduction in STEMI patients with a 70% resolution cut-off

Trial Locations

Locations (1)

Department of Cardiology

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Bydgoszcz, Kujawsko-Pomorskie, Poland

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