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Ticagrelor and preconditioning in patients with stable coronary artery disease (TAPER-S): a randomized pilot clinical trial
- Source :
- Trials, Vol 21, Iss 1, Pp 1-13 (2020), Trials
- Publication Year :
- 2020
-
Abstract
- Background Ticagrelor is a reversibly binding, direct-acting, oral, P2Y12 antagonist used for the prevention of atherothrombotic events in patients with coronary artery disease (CAD). Ticagrelor blocks adenosine reuptake through the inhibition of equilibrative nucleoside transporter 1 (ENT-1) on erythrocytes and platelets, thereby facilitating adenosine-induced physiological responses such as an increase in coronary blood flow velocity. Meanwhile, adenosine plays an important role in triggering ischemic preconditioning through the activation of the A1 receptor. Therefore, an increase in ticagrelor-enhanced adenosine bioavailability may confer beneficial effects through mechanisms related to preconditioning activation and improvement of coronary microvascular dysfunction. Methods To determine whether ticagrelor can trigger ischemic preconditioning and influence microvascular function, we designed this prospective, open-label, pilot study that enrolled patients with stable multivessel CAD requiring staged, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI). Participants will be randomized in 1:1 ratios either to ticagrelor (loading dose (LD) 180 mg, maintenance dose (MD) 90 mg bid) or to clopidogrel (LD 600 mg, MD 75 mg) from 3 to 1 days before the scheduled PCI. The PCI operators will be blinded to the randomization arm. The primary endpoint is the delta (difference) between ST segment elevations (in millimeters, mm) as assessed by intracoronary electrocardiogram (ECG) during the two-step sequential coronary balloon inflation in the culprit vessel. Secondary endpoints are 1) changes in coronary flow reserve (CFR), index of microvascular resistance (IMR), and FFR measured in the culprit vessel and reference vessel at the end of PCI, and 2) angina score during inflations. This study started in 2018 with the aim of enrolling 100 patients. Based on the rate of negative FFR up to 30% and a drop-out rate up to 10%, we expect to detect an absolute difference of 4 mm among the study arms in the mean change of ST elevation following repeated balloon inflations. All study procedures were reviewed and approved by the Ethical Committee of the Catholic University of Sacred Heart. Discussion Ticagrelor might improve ischemia tolerance and microvascular function compared to clopidogrel, and these effects might translate to better long-term clinical outcomes. Trial registration EudraCT No. 2016–004746-28. No. NCT02701140. Trial status Information provided in this manuscript refers to the definitive version (n. 3.0) of the study protocol, dated 31 October 2017, and includes all protocol amendments. Recruitment started on 18 September 2018 and is currently ongoing. The enrollment is expected to be completed by the end of 2019. Trial sponsor Fondazione Policlinico Universitario A. Gemelli – Roma, Polo di Scienze Cardiovascolari e Toraciche, Largo Agostino Gemelli 8, 00168 Rome, Italy.
- Subjects :
- Male
Ticagrelor
Adenosine
medicine.medical_treatment
Medicine (miscellaneous)
Pilot Projects
Fractional flow reserve
Coronary Artery Disease
Coronary artery disease
Angina
Study Protocol
Pharmacology (medical)
Randomized Controlled Trials as Topic
lcsh:R5-920
Middle Aged
Clopidogrel
Coronary Vessels
Fractional Flow Reserve, Myocardial
Treatment Outcome
Microvascular dysfunction
Intracoronary electrocardiography
Ischemic Preconditioning, Myocardial
Cardiology
Microvascular resistance
Female
lcsh:Medicine (General)
medicine.drug
Adult
medicine.medical_specialty
Adolescent
Ischemic preconditioning
Microvascular function
Myocardial Reperfusion Injury
Young Adult
Clinical Trials, Phase II as Topic
Percutaneous Coronary Intervention
Internal medicine
Preoperative Care
medicine
Humans
Aged
business.industry
Coronary flow reserve
Percutaneous coronary intervention
medicine.disease
Clinical Trials, Phase III as Topic
Conventional PCI
Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE
Microvessels
Purinergic P2Y Receptor Antagonists
Vascular Resistance
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Trials, Vol 21, Iss 1, Pp 1-13 (2020), Trials
- Accession number :
- edsair.doi.dedup.....61db947f90f9ed7548c741ff338d5bfd