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

Sponsor

Centre Hospitalier Universitaire Vaudois (Other)

Overall Status

Completed

CT.gov ID

NCT02531165

Collaborator

AstraZeneca (Industry)

Enrollment

Location

Arms

29.2

Duration (Months)

1.3

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myocardial Infarction	Drug: Fentanyl Drug: Morphine Drug: Ticagrelor Drug: Aspirin Drug: Unfractioned Heparin Procedure: Primary PCI	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

38 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Sep 1, 2015

Actual Primary Completion Date :

Feb 6, 2018

Actual Study Completion Date :

Feb 6, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Morphine 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 Analgesia protocol using Morphine (initial dose: 4-8 mg, additional doses of 2 mg every 5-15 minutes to achieve adequate sedation, if required). Drug: Ticagrelor Pre-hospital Ticagrelor loading dose of 180 mg administered orally, followed by 90 mg bid Other Names: Brilique Drug: Aspirin 500 mg loading dose orally (or intravenously), followed by 100 mg od Drug: 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.
Experimental: Fentanyl 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 Analgesia protocol using Fentanyl (initial dose: 50-100 mcg, additional doses of 25 mcg every 2-5 minutes to achieve adequate sedation, if required). Drug: Ticagrelor Pre-hospital Ticagrelor loading dose of 180 mg administered orally, followed by 90 mg bid Other Names: Brilique Drug: Aspirin 500 mg loading dose orally (or intravenously), followed by 100 mg od Drug: 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.

Arm

Intervention/Treatment

Experimental: Morphine

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

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

Drug: Ticagrelor

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

Other Names:

Brilique

Drug: Aspirin

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

Drug: 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.

Experimental: Fentanyl

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

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

Drug: Ticagrelor

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

Other Names:

Brilique

Drug: Aspirin

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

Drug: 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.

Outcome Measures

Primary Outcome Measures

Residual platelet reactivity (PR) by Platelet Reactivity Units (PRU) [2 hours after loading dose of Ticagrelor]

Secondary Outcome Measures

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]
Proportion of patients with 70% or greater resolution of the ST-segment elevation before PCI [at 2 hours]
Proportion of patients without Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography [at 2 hours]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.