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

ST Elevation Myocardial Infarction Clinical Trial

— ANEMON  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04476173
• Other study ID #: ANEMON-SIRIO3
• Status: Recruiting
• Phase: Phase 3
• Start date: June 1, 2020
• Est. completion date: December 30, 2024

Study information

• Verified date: September 2023
• Source: Collegium Medicum w Bydgoszczy
• Contact: Agata Kosobucka, PhD
• Phone: +48 525854023
• Email: akosobucka[@]wp.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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 information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Infarction
• Myocardial Infarction
• Non ST Segment Elevation Acute Coronary Syndrome
• ST Elevation Myocardial Infarction

Intervention

Drug:
• Methoxyflurane - Penthrox
ACS patients who received inhaled methoxyflurane as analgesic treatment
• Morphine
ACS patients who received intravenous morphine as analgesic treatment

Locations

Country	Name	City	State
Poland	Department of Cardiology	Bydgoszcz	Kujawsko-Pomorskie

Sponsors (1)

Lead Sponsor	Collaborator
Collegium Medicum w Bydgoszczy

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	NPRS score before and 2-3 minutes after drug administration in each study arm	2-3 mins
Primary	Measure of pain intensity according to the Numeric Pain Rating Scale (NPRS) immediately after PCI in relation to pain intensity assessed before drug administration	NPRS score before drug administration and and immediately after PCI in each study arm	immediately after PCI
Secondary	Adverse effects of evaluated therapies	nausea, vomiting, dry mouth, respiratory failure - need for intubation, headache, dizziness, drowsiness, loss of consciousness, death	24 hours
Secondary	Need for GPIIb/IIIa (glycoprotein IIb/IIIa) inhibitor administration during PCI due to large intracoronary thrombus	The percentage of patients who required GP IIb/IIIa administration in each study arm	24 hours
Secondary	Angiographic effect of PCI using Thrombolysis In Myocardial Infarction (TIMI) scale	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)	through study completion, an average of 1 year
Secondary	Angiographic effect of PCI using TIMI Myocardial Perfusion Grade (TMPG) scale	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)	through study completion, an average of 1 year
Secondary	ST elevation resolution in STEMI patients after PCI	central analysis of ST elevation reduction in STEMI patients with a 70% resolution cut-off	1 hour after PCI