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Influence of METHoxyflurane on ANtiplatelet Effect of Ticagrelor in Patients With Unstable Angina Pectoris (METHANE)

Primary Purpose

Unstable Angina

Status
Recruiting
Phase
Phase 4
Locations
Poland
Study Type
Interventional
Intervention
Ticagrelor followed with Methoxyflurane
Ticagrelor followed with Morphine
Ticagrelor alone
Sponsored by
Collegium Medicum w Bydgoszczy
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Unstable Angina

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Provision of informed consent prior to any study specific procedures
  • Diagnosis of unstable angina
  • Male or non-pregnant female, aged 18-80 years
  • Provision of informed consent for angiography and PCI
  • GRACE score <140 pts

Exclusion Criteria:

  • Treatment with ticlopidine, clopidogrel, prasugrel or ticagrelor within 14 days before the study enrollment
  • Current treatment with morphine or any opioid "mi" receptor agonist
  • Hypersensitivity to ticagrelor
  • Current treatment with oral anticoagulant or chronic therapy with low-molecular-weight heparin
  • Active bleeding
  • History of intracranial hemorrhage
  • Recent gastrointestinal bleeding (within 30 days)
  • History of coagulation disorders
  • Platelet count less than <100 x10^3/mcl
  • Hemoglobin concentration less than 10.0 g/dl
  • History of moderate or severe hepatic impairment
  • History of major surgery or severe trauma (within 3 months)
  • Risk of bradycardic events as judged by the investigator
  • Second- or third-degree atrioventricular block during screening for eligibility
  • History of asthma or severe chronic obstructive pulmonary disease
  • Kidney disease requiring dialysis
  • Manifest infection or inflammatory state
  • Killip class III or IV during screening for eligibility
  • Respiratory failure
  • History of severe chronic heart failure (NYHA class III or IV)
  • Concomitant therapy with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir) or strong CYP3A inducers (rifampicin, phenytoin, carbamazepine, dexamethasone, phenobarbital) within 14 days and during study treatment
  • Body weight below 50 kg

Sites / Locations

  • Cardiology Department, Dr. A. Jurasz University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

Ticagrelor followed with methoxyflurane

Ticagrelor followed with morphine

Ticagrelor

Arm Description

patients who received ticagrelor followed with inhaled methoxyflurane due to unstable angina

patients who received ticagrelor followed with intravenous morphine due to unstable angina

patients who received ticagrelor without any analgesia due to unstable angina

Outcomes

Primary Outcome Measures

Mean platelet reactivity between the study arms
Mean platelet reactivity between the study arms, assessed using the Multiplate Analyzer

Secondary Outcome Measures

The percentage of high platelet reactivity patients (HPR) throughout the study period
the percentage of patients with high platelet reactivity throughout the study period
Mean time to achieve platelet reactivity below the threshold for HPR
Mean time required for patients to receive low platelet reactivity in each study arm
area under the plasma concentration-time curve for ticagrelor and its active metabolite between the study arms
area under the plasma concentration-time curve for ticagrelor and its active metabolite between the study arms

Full Information

First Posted
June 19, 2020
Last Updated
September 8, 2023
Sponsor
Collegium Medicum w Bydgoszczy
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1. Study Identification

Unique Protocol Identification Number
NCT04442919
Brief Title
Influence of METHoxyflurane on ANtiplatelet Effect of Ticagrelor in Patients With Unstable Angina Pectoris
Acronym
METHANE
Official Title
Influence of METHoxyflurane on ANtiplatelet Effect of Ticagrelor in Patients With Unstable Angina Pectoris - METHANE Study
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2020 (Actual)
Primary Completion Date
October 30, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Collegium Medicum w Bydgoszczy

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to evaluate differences in the pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite in patients who received ticagrelor followed with methoxyflurane versus ticagrelor followed with morphine or ticagrelor alone due to unstable angina pectoris
Detailed Description
Results of the IMPRESSION trial published in 2015 proved that morphine use in patients with acute coronary syndromes (ACS) is associated with undesirable impact on pharmacokinetics (PK) and pharmacodynamics (PD) of ticagrelor. Despite that, morphine is still a standard analgesic treatment in ACS patients and it should not be routinely withdrawn. Based on contemporary knowledge, morphine, acting via mi-opioid receptors, was found to inhibit gastrointestinal motility or induce adverse effects such as nausea or vomiting. We decided to design a clinical study aiming to evaluate the impact of methoxyflurane on PD of ticagrelor in patients diagnosed with unstable angina pectoris (UA). Methoxyflurane is an inhaled anesthetic, registered in Poland in emergency medicine for pain alleviation in trauma patients. The drug was widely used in 1960s to induce general anesthesia, however its clinical utility was reduced with the development of novel anesthetic agents. Taking into account its different mechanism of action, it can be presumed that, contrary to morphine, no respiratory depression should be observed as well as no attenuation or delay of antiaggregatory effect of ticagrelor should occur, as no interaction with mi-receptor in gastrointestinal tract is related to activity of methoxyflurane. Patients will be randomized in a 1:1:1 ratio into the study arms as follows: 1) 180 mg ticagrelor (2 integral tablets of 90 mg ticagrelor) followed by 3 mg inhaled methoxyflurane, 2) 180 mg ticagrelor followed by 5 mg intravenous morphine, 3) 180 mg ticagrelor alone

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Unstable Angina

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ticagrelor followed with methoxyflurane
Arm Type
Experimental
Arm Description
patients who received ticagrelor followed with inhaled methoxyflurane due to unstable angina
Arm Title
Ticagrelor followed with morphine
Arm Type
Active Comparator
Arm Description
patients who received ticagrelor followed with intravenous morphine due to unstable angina
Arm Title
Ticagrelor
Arm Type
Active Comparator
Arm Description
patients who received ticagrelor without any analgesia due to unstable angina
Intervention Type
Drug
Intervention Name(s)
Ticagrelor followed with Methoxyflurane
Other Intervention Name(s)
Brilique + Penthrox
Intervention Description
patients who received ticagrelor followed with inhaled methoxyflurane due to unstable angina
Intervention Type
Drug
Intervention Name(s)
Ticagrelor followed with Morphine
Other Intervention Name(s)
Brilique + Morphine
Intervention Description
patients who received ticagrelor followed with intravenous morphine due to unstable angina
Intervention Type
Drug
Intervention Name(s)
Ticagrelor alone
Other Intervention Name(s)
Brilique
Intervention Description
patients who received ticagrelor without any analgesia due to unstable angina
Primary Outcome Measure Information:
Title
Mean platelet reactivity between the study arms
Description
Mean platelet reactivity between the study arms, assessed using the Multiplate Analyzer
Time Frame
6 hours
Secondary Outcome Measure Information:
Title
The percentage of high platelet reactivity patients (HPR) throughout the study period
Description
the percentage of patients with high platelet reactivity throughout the study period
Time Frame
6 hours
Title
Mean time to achieve platelet reactivity below the threshold for HPR
Description
Mean time required for patients to receive low platelet reactivity in each study arm
Time Frame
6 hours
Title
area under the plasma concentration-time curve for ticagrelor and its active metabolite between the study arms
Description
area under the plasma concentration-time curve for ticagrelor and its active metabolite between the study arms
Time Frame
6 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provision of informed consent prior to any study specific procedures Diagnosis of unstable angina Male or non-pregnant female, aged 18-80 years Provision of informed consent for angiography and PCI GRACE score <140 pts Exclusion Criteria: Treatment with ticlopidine, clopidogrel, prasugrel or ticagrelor within 14 days before the study enrollment Current treatment with morphine or any opioid "mi" receptor agonist Hypersensitivity to ticagrelor Current treatment with oral anticoagulant or chronic therapy with low-molecular-weight heparin Active bleeding History of intracranial hemorrhage Recent gastrointestinal bleeding (within 30 days) History of coagulation disorders Platelet count less than <100 x10^3/mcl Hemoglobin concentration less than 10.0 g/dl History of moderate or severe hepatic impairment History of major surgery or severe trauma (within 3 months) Risk of bradycardic events as judged by the investigator Second- or third-degree atrioventricular block during screening for eligibility History of asthma or severe chronic obstructive pulmonary disease Kidney disease requiring dialysis Manifest infection or inflammatory state Killip class III or IV during screening for eligibility Respiratory failure History of severe chronic heart failure (NYHA class III or IV) Concomitant therapy with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir) or strong CYP3A inducers (rifampicin, phenytoin, carbamazepine, dexamethasone, phenobarbital) within 14 days and during study treatment Body weight below 50 kg
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Piotr Niezgoda, MD
Phone
+48 52 585 4023
Email
piotr.niezgoda1986@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacek Kubica, Professor
Organizational Affiliation
Collegium Medicum w Bydgoszczy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cardiology Department, Dr. A. Jurasz University Hospital
City
Bydgoszcz
State/Province
Kujawsko-Pomorskie
ZIP/Postal Code
85-094
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Piotr Niezgoda, M.D.
Phone
+48525854023
Email
piotr.niezg@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Influence of METHoxyflurane on ANtiplatelet Effect of Ticagrelor in Patients With Unstable Angina Pectoris

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