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

NCT02531165 | Completed DMC

• 1 other identifier: ESR14-10591
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myocardial Infarction

Outcome Measures

Primary Outcomes (1)

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

  2 hours after loading dose of Ticagrelor

Secondary Outcomes (7)

• Residual PR by PRU

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

• High on Treatment Platelet Reactivity (HTPR) rates

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

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

  at 1, 2, 4, 6 and 12 hours

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

  at 1, 2, 4, 6 and 12 hours

• Area under the plasma concentration-time curve of Ticagrelor

  at 1, 2, 4, 6 and 12 hours

Study Arms (2)

Morphine

EXPERIMENTAL

* 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.

Drug: Morphine; Drug: Ticagrelor; Drug: Aspirin; Drug: Unfractioned Heparin; Procedure: Primary PCI

Fentanyl

EXPERIMENTAL

* 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.

Drug: Fentanyl; Drug: Ticagrelor; Drug: Aspirin; Drug: Unfractioned Heparin; Procedure: Primary PCI

Interventions

Fentanyl DRUG

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

Fentanyl

Morphine DRUG

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

Morphine

Ticagrelor DRUG

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

Also known as: Brilique

Fentanyl; Morphine

Aspirin DRUG

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

Fentanyl; Morphine

Unfractioned Heparin DRUG

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

Fentanyl; Morphine

Primary PCI PROCEDURE

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

Fentanyl; Morphine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead
• AstraZeneca: collaborator

Study Sites (1)

Centre Hospitalier Universitaire Vaudois

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 33347326 DERIVED

• 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.

  PMID: 30101278 DERIVED

MeSH Terms

Interventions

Fentanyl; Morphine; Ticagrelor; Aspirin

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Juan F. Iglesias, MD

  Centre Hospitalier Universitaire Vaudois

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: August 18, 2015
• First Posted: August 24, 2015
• Study Start: September 1, 2015
• Primary Completion: February 6, 2018
• Study Completion: February 6, 2018
• Last Updated: July 15, 2020

Record last verified: 2018-02

Locations

CH (1)