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Platelet Inhibition After Pre-hospital Ticagrelor Using Fentanyl Compared to Morphine in Patients With ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention (PERSEUS)

Primary Purpose

Acute Myocardial Infarction

Status

Completed

Phase

Not Applicable

Locations

Switzerland

Study Type

Interventional

Intervention

Fentanyl

Morphine

Ticagrelor

Aspirin

Unfractioned Heparin

Primary PCI

About this trial

This is an interventional treatment trial for Acute Myocardial Infarction

Eligibility Criteria

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

Inclusion Criteria:

Age >18-year-old
STEMI within 12 hours of symptoms' onset eligible for primary PCI with stent implantation.
Patient able to give written informed consent.

Exclusion Criteria:

Contraindication, intolerance or hypersensitivity to Ticagrelor, or any excipients
Contraindication, intolerance or hypersensitivity to Morphine, Fentanyl, or any excipients
Active bleeding or bleeding diathesis
History of intracranial haemorrhage
Chronic oral anticoagulation treatment
Previous antiplatelet treatment
Contraindications to antiplatelet therapy
Severe renal insufficiency (creatinine clearance <30 mL/min)
Severe hepatic dysfunction
Severe chronic obstructive pulmonary disease
Periprocedural glycoprotein IIb/IIIa inhibitors administration
Relevant haematological disease
Patient who is currently, plans, or has been enrolled in another clinical study involving use of an investigational drug or device within the prior 30 days.
If female, patient pregnant or breastfeeding.

Sites / Locations

Centre Hospitalier Universitaire Vaudois

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Morphine

Fentanyl

Arm Description

Pre-hospital Ticagrelor 180 mg loading dose orally. Morphine, initial dose: 4-8 mg, additional doses of 2 mg every 5-15 minutes to achieve adequate sedation, if required. Aspirin 500 mg loading dose orally (or intravenously). Unfractioned heparin 5'000 IU loading dose intravenously, additional doses to achieve an ACT >250 sec during PCI are allowed. Primary PCI.

Pre-hospital Ticagrelor 180 mg loading dose orally. Fentanyl, initial dose: 50-100 mcg, additional doses of 25 mcg every 2-5 minutes to achieve adequate sedation, if required. Aspirin 500 mg loading dose orally (or intravenously). Unfractioned heparin 5'000 IU loading dose intravenously, additional doses to achieve an ACT >250 sec during PCI are allowed. Primary PCI.

Outcomes

Primary Outcome Measures

Residual platelet reactivity (PR) by Platelet Reactivity Units (PRU)

Secondary Outcome Measures

Residual PR by PRU

High on Treatment Platelet Reactivity (HTPR) rates

Peak plasma concentration (Cmax) of Ticagrelor and AR-C124910XX

Time to peak plasma concentration (tmax) of Ticagrelor and AR-C124910XX

Area under the plasma concentration-time curve of Ticagrelor

Proportion of patients with 70% or greater resolution of the ST-segment elevation before PCI

Proportion of patients without Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography

Full Information

NCT ID

NCT02531165

First Posted

August 18, 2015

Last Updated

July 13, 2020

Sponsor

Centre Hospitalier Universitaire Vaudois

Collaborators

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT02531165

Brief Title

Platelet Inhibition After Pre-hospital Ticagrelor Using Fentanyl Compared to Morphine in Patients With ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Acronym

PERSEUS

Official Title

Comparison of Analgesia With Fentanyl and Morphine on Platelet Inhibition After Pre-hospital Ticagrelor Administration in Patients With ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Study Type

Interventional

2. Study Status

Record Verification Date

February 2018

Overall Recruitment Status

Completed

Study Start Date

September 2015 (undefined)

Primary Completion Date

February 6, 2018 (Actual)

Study Completion Date

February 6, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Centre Hospitalier Universitaire Vaudois

Collaborators

AstraZeneca

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Prospective, randomized, open-label, single-center, investigator-initiated trial, including patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) within 12 hours of the symptom's onset. The study aims to compare platelet inhibition (pharmacodynamics and pharmacokinetics) of pre-hospital Ticagrelor in patients with STEMI according to two different analgesia protocols using Fentanyl or Morphine.

Detailed Description

Consecutive patients with acute STEMI within 12 hours of the symptoms' onset and candidates for PPCI will be screened for inclusion in the study. Eligible patients who require analgesia for the relief of acute chest pain, defined as Visual Analogue Scale ≥3, will be randomized in a 1:1 ratio into one of the two treatment arms to receive analgesia with either Morphine or Fentanyl following administration of a pre-hospital loading dose of Ticagrelor. Randomized patients will undergo primary PCI and managed according to the current guidelines of the European Society of Cardiology. Blood samples (10 ml) will be collected at 0, 1, 2, 4, 6, 12 and 24 hours after the loading dose of Ticagrelor to assess platelet inhibition using the VerifyNow P2Y12 function and the Vasodilator-Stimulated-phosphoprotein Phosphorylation (VASP) assays, plasma concentration of Ticagrelor and its active metabolite (AR-C124910XX) using a validated liquid chromatography/mass spectrometry detection method and the procoagulant action of platelets.

6. Conditions and Keywords

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

Acute Myocardial Infarction

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

38 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Morphine

Arm Type

Experimental

Arm Description

Arm Title

Fentanyl

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Fentanyl

Intervention Description

Analgesia protocol using Fentanyl (initial dose: 50-100 mcg, additional doses of 25 mcg every 2-5 minutes to achieve adequate sedation, if required).

Intervention Type

Drug

Intervention Name(s)

Morphine

Intervention Description

Analgesia protocol using Morphine (initial dose: 4-8 mg, additional doses of 2 mg every 5-15 minutes to achieve adequate sedation, if required).

Intervention Type

Drug

Intervention Name(s)

Ticagrelor

Other Intervention Name(s)

Brilique

Intervention Description

Pre-hospital Ticagrelor loading dose of 180 mg administered orally, followed by 90 mg bid

Intervention Type

Drug

Intervention Name(s)

Aspirin

Intervention Description

500 mg loading dose orally (or intravenously), followed by 100 mg od

Intervention Type

Drug

Intervention Name(s)

Unfractioned Heparin

Intervention Description

5'000 IU loading dose intravenously, additional doses to achieve an ACT >250 sec during PCI are allowed.

Intervention Type

Procedure

Intervention Name(s)

Primary PCI

Intervention Description

Primary PCI with stent implantation according to the guidelines of the European Society of Cardiology.

Primary Outcome Measure Information:

Title

Residual platelet reactivity (PR) by Platelet Reactivity Units (PRU)

Time Frame

2 hours after loading dose of Ticagrelor

Secondary Outcome Measure Information:

Title

Residual PR by PRU

Time Frame

0, 1, 4, 6, 12 and 24 hours after the loading dose of Ticagrelor

Title

High on Treatment Platelet Reactivity (HTPR) rates

Time Frame

0, 1, 2, 4, 6, 12 and 24 hours after the loading dose of Ticagrelor

Title

Peak plasma concentration (Cmax) of Ticagrelor and AR-C124910XX

Time Frame

at 1, 2, 4, 6 and 12 hours

Title

Time to peak plasma concentration (tmax) of Ticagrelor and AR-C124910XX

Time Frame

at 1, 2, 4, 6 and 12 hours

Title

Area under the plasma concentration-time curve of Ticagrelor

Time Frame

at 1, 2, 4, 6 and 12 hours

Title

Proportion of patients with 70% or greater resolution of the ST-segment elevation before PCI

Time Frame

at 2 hours

Title

Proportion of patients without Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography

Time Frame

at 2 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age >18-year-old STEMI within 12 hours of symptoms' onset eligible for primary PCI with stent implantation. Patient able to give written informed consent. Exclusion Criteria: Contraindication, intolerance or hypersensitivity to Ticagrelor, or any excipients Contraindication, intolerance or hypersensitivity to Morphine, Fentanyl, or any excipients Active bleeding or bleeding diathesis History of intracranial haemorrhage Chronic oral anticoagulation treatment Previous antiplatelet treatment Contraindications to antiplatelet therapy Severe renal insufficiency (creatinine clearance <30 mL/min) Severe hepatic dysfunction Severe chronic obstructive pulmonary disease Periprocedural glycoprotein IIb/IIIa inhibitors administration Relevant haematological disease Patient who is currently, plans, or has been enrolled in another clinical study involving use of an investigational drug or device within the prior 30 days. If female, patient pregnant or breastfeeding.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Juan F. Iglesias, MD

Organizational Affiliation

Centre Hospitalier Universitaire Vaudois

Official's Role

Principal Investigator

Facility Information:

Facility Name

Centre Hospitalier Universitaire Vaudois

City

Lausanne

State/Province

Vaud

ZIP/Postal Code

1011

Country

Switzerland

12. IPD Sharing Statement

Citations:

PubMed Identifier

33347326

Citation

Iglesias JF, Valgimigli M, Carbone F, Lauriers N, Giorgio Masci P, Degrauwe S. Effects of Fentanyl Versus Morphine on Ticagrelor-Induced Platelet Inhibition in Patients With ST-Segment Elevation Myocardial Infarction: The PERSEUS Randomized Trial. Circulation. 2020 Dec 22;142(25):2479-2481. doi: 10.1161/CIRCULATIONAHA.120.049287. Epub 2020 Dec 21. No abstract available.

Results Reference

derived

PubMed Identifier

30101278

Citation

Degrauwe S, Roffi M, Lauriers N, Muller O, Masci PG, Valgimigli M, Iglesias JF. Influence of intravenous fentanyl compared with morphine on ticagrelor absorption and platelet inhibition in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: rationale and design of the PERSEUS randomized trial. Eur Heart J Cardiovasc Pharmacother. 2019 Jul 1;5(3):158-163. doi: 10.1093/ehjcvp/pvy031.

Results Reference

derived

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Platelet Inhibition After Pre-hospital Ticagrelor Using Fentanyl Compared to Morphine in Patients With ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

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