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

Acute Myocardial Infarction Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02531165
• Other study ID #: ESR14-10591
• Status: Completed
• Phase: N/A
• Start date: September 2015
• Est. completion date: February 6, 2018

Study information

• Verified date: February 2018
• Source: Centre Hospitalier Universitaire Vaudois
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: February 6, 2018
• Est. primary completion date: February 6, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Infarction
• Myocardial Infarction
• ST Elevation Myocardial Infarction

Intervention

Drug:
• Fentanyl
Analgesia protocol using Fentanyl (initial dose: 50-100 mcg, additional doses of 25 mcg every 2-5 minutes to achieve adequate sedation, if required).
• Morphine
Analgesia protocol using Morphine (initial dose: 4-8 mg, additional doses of 2 mg every 5-15 minutes to achieve adequate sedation, if required).
• Ticagrelor
Pre-hospital Ticagrelor loading dose of 180 mg administered orally, followed by 90 mg bid
• Aspirin
500 mg loading dose orally (or intravenously), followed by 100 mg od
• Unfractioned Heparin
5'000 IU loading dose intravenously, additional doses to achieve an ACT >250 sec during PCI are allowed.

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

Locations

Country	Name	City	State
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne	Vaud

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire Vaudois	AstraZeneca

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Residual platelet reactivity (PR) by Platelet Reactivity Units (PRU)		2 hours after loading dose of Ticagrelor
Secondary	Residual PR by PRU		0, 1, 4, 6, 12 and 24 hours after the loading dose of Ticagrelor
Secondary	High on Treatment Platelet Reactivity (HTPR) rates		0, 1, 2, 4, 6, 12 and 24 hours after the loading dose of Ticagrelor
Secondary	Peak plasma concentration (Cmax) of Ticagrelor and AR-C124910XX		at 1, 2, 4, 6 and 12 hours
Secondary	Time to peak plasma concentration (tmax) of Ticagrelor and AR-C124910XX		at 1, 2, 4, 6 and 12 hours
Secondary	Area under the plasma concentration-time curve of Ticagrelor		at 1, 2, 4, 6 and 12 hours
Secondary	Proportion of patients with 70% or greater resolution of the ST-segment elevation before PCI		at 2 hours
Secondary	Proportion of patients without Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography		at 2 hours