Clinical trial NCT04476173: ANalgesic Efficacy and Safety of MOrphiNe Versus Methoxyflurane in Patients With Acute Myocardial Infarction
Official title: ANalgesic Efficacy and Safety of MOrphiNe Versus Methoxyflurane in Patients With Acute Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: ST Elevation Myocardial Infarction
Non ST Segment Elevation Acute Coronary Syndrome
Lead sponsor: Collegium Medicum w Bydgoszczy
Sponsor class: OTHER
First posted: 2020-07-17
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: 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 administration
timeFrame: 2-3 mins
measure: Measure of pain intensity according to the Numeric Pain Rating Scale (NPRS) immediately after PCI in relation to pain intensity assessed before drug administration
timeFrame: immediately after PCI
Secondary outcomes:
measure: Adverse effects of evaluated therapies
timeFrame: 24 hours
measure: Need for GPIIb/IIIa (glycoprotein IIb/IIIa) inhibitor administration during PCI due to large intracoronary thrombus
timeFrame: 24 hours
measure: Angiographic effect of PCI using Thrombolysis In Myocardial Infarction (TIMI) scale
timeFrame: through study completion, an average of 1 year
measure: Angiographic effect of PCI using TIMI Myocardial Perfusion Grade (TMPG) scale
timeFrame: through study completion, an average of 1 year
measure: ST elevation resolution in STEMI patients after PCI
timeFrame: 1 hour after PCI
Other outcomes:
Locations:
city: Bydgoszcz
country: Poland
facility: Department of Cardiology
state: Kujawsko-Pomorskie
Study officials:
affiliation: Collegium Medicum w Bydgoszczy
name: Jacek Kubica, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kubica A, Kosobucka A, Niezgoda P, Adamski P, Buszko K, Lesiak M, Wojakowski W, Gasior M, Goracy J, Kleinrok A, Nadolny K, Navarese E, Kubica J. ANalgesic Efficacy and safety of MOrphiNe versus methoxyflurane in patients with acute myocardial infarction: the rationale and design of the ANEMON-SIRIO 3 study: a multicentre, open-label, phase II, randomised clinical trial. BMJ Open. 2021 Mar 1;11(3):e043330. doi: 10.1136/bmjopen-2020-043330.