Clinical trial NCT04654052: VerifyNow to Optimise Platelet Inhibition in Coronary Acute Syndrome
Official title: VerifyNow to Optimise Platelet Inhibition in Coronary Acute Syndrome (VERONICA Trial)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Acute Coronary Syndrome
Acute Myocardial Infarction
Coronary Artery Disease
Percutaneous Coronary Intervention
Keywords: Antiplatelet therapy
Platelet Aggregation Inhibitors
Platelet Function Test
Ticagrelor
Clopidogrel
Prasugrel
Lead sponsor: Fundación EPIC
Sponsor class: OTHER
First posted: 2020-12-04
Enrollment: 634
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the study is to establish a de-scaling strategy of P2Y12 inhibitors (P2Y12 i) with a decrease in hemorrhagic events without increasing ischemic complications based on a Platelet Function Test (PFT).

Detailed description: Clinical practice guidelines recommend the use of double anti-aggregation with acetylsalicylic acid and a P2Y12 receptor inhibitor (P2Y12 i) in acute coronary syndrome (ACS) and in the choice of the latter it is very important to consider two opposing risks, Ischemia and hemorrhage. In the era of clopidogrel, platelet function tests (PFT) attempted to determine which patients were at risk of thrombotic events, but after the publication of 3 randomized studies, the absence of benefit from the use of PFT was proven except in very selected cases. The TOPIC trial opened the door to the descaling strategy of P2Y12 i with a decrease in hemorrhagic events without increasing ischemic complications. In that study, where the randomization was not based on PFT, it was demonstrated that there is a subgroup of patients who with prasugrel and ticagrelor pose an excessive level of antiaggregation and carry a high rate of complications, as high as 33 % in the net clinical end-point of ischemia and bleeding BARC ≥ 2 at 1 year. Based on that data, the recently published guidelines of the non-ST acute coronary syndrome of the European Society of Cardiology recommend with class IIB that de-escalation of P2Y12 i maybe considered an alternative strategy, especially in ACS patients deemed unsuitable for potent platelet inhibition. De-escalation may be done based on clinical judgment, or guided by platelet function testing, or CYP2C19 genotyping depending on the patient's risk profile and availability of respective assays. In VERONICA, The researchers try to demonstrate with the current study the usefulness of PFT to diagnose patients with excessive level of antiaggregation and to see if in them a descaling strategy similar to that of TOPIC could be associated with a decrease in the combined ischemia and hemorrhage events. We propose a prospective, randomized and multicentre trial in patients with ACS who have been treated with acetylsalicylic acid (AAS) + ticagrelor or prasugrel. After 1 month of discharge, antiaggregation measurement will be carried out with the VerifyNow® device (Werfen, Spain) and those with PRU ≤30 will be randomized 1:1 to continue with ticagrelor or prasugrel(control branch) vs. de-escalation to clopidogrel (intervention branch) for the remaining 11 months. The primary end-point will be the rate of the combined net clinical benefit consisting of cardiovascular death, nonfatal acute myocardial infarction (AMI), nonfatal stroke and bleeding BARC ≥2 at 12 months. The total number of randomized patients will be 634 and there will be subgroup analysis of the primary end-point by diabetes, type of acute coronary syndrome or type of drug (ticagrelor or prasugrel).

Eligibility criteria: Inclusion Criteria:

* Patients with age 18 years or above.
* Patient is able to understand the nature of study and has provided written informed consent.
* Patients with Acute Coronary Syndrome and who underwent PCI during the admission, who have been discharged on double. antiplatelet therapy with Acetylsalicylic Acid and Ticagrelor or Prasugrel.

Exclusion Criteria:

* Patients with history of intracranial bleeding.
* Patients with contraindication for the use of Acetylsalicylic Acid or Clopidogrel or Ticagrelor or Prasugrel.
* Patients with major ischemic or hemorrhagic events during the first month.
* Patients with Thrombocytopenia \<50,000 /µL.
* Patients with permanent oral anticoagulation.
* Patient is pregnant or breast feeding.
* Patients with impossibility to complete 1 year of follow-up.
* Patient´s life-expectancy is less than 24 months.

Primary outcomes:
measure: Incidence of Net Adverse Cardiac Events (NACE)
timeFrame: 12 months
Secondary outcomes:
measure: Incidence of Death (Cardiovascular)
timeFrame: 12 months
measure: Incidence of Death
timeFrame: 12 months
measure: Incidence of Non fatal Myocardial Infarction (MI)
timeFrame: 12 months
measure: Incidence of Stroke
timeFrame: 12 months
measure: Incidence of Thrombosis in target lesion
timeFrame: 12 months
measure: Incidence of revascularization on target lesion
timeFrame: 12 months
measure: Incidence of (BARC criteria ≥ 2)
timeFrame: 12 months
Other outcomes:
Locations:
city: El Palmar
country: Spain
facility: Hospital Universitario Virgen de La Arrixaca
state: Murcia
city: Albacete
country: Spain
facility: Hospital General Universitario de Albacete
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D Hebron
city: Ciudad Real
country: Spain
facility: Hospital General Universitario de Ciudad Real
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Galdakao
country: Spain
facility: Hospital Universitario de Galdakao-Usansolo
city: Gijón
country: Spain
facility: Hospital Universitario de Cabueñes
city: Granada
country: Spain
facility: Hospital Universitario Virgen de Las Nieves
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
city: Huelva
country: Spain
facility: Hospital Universitario Juan Ramon Jimenez
city: León
country: Spain
facility: Hospital de León
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Agusti
city: Málaga
country: Spain
facility: Hospital Universitario Regional de Malaga
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Valladolid
country: Spain
facility: Hospital Clinico Universitario de Valladolid
city: Zaragoza
country: Spain
facility: Hospital Universitario Lozano Blesa
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
References:
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citation: Cayla G, Cuisset T, Silvain J, Leclercq F, Manzo-Silberman S, Saint-Etienne C, Delarche N, Bellemain-Appaix A, Range G, El Mahmoud R, Carrie D, Belle L, Souteyrand G, Aubry P, Sabouret P, du Fretay XH, Beygui F, Bonnet JL, Lattuca B, Pouillot C, Varenne O, Boueri Z, Van Belle E, Henry P, Motreff P, Elhadad S, Salem JE, Abtan J, Rousseau H, Collet JP, Vicaut E, Montalescot G; ANTARCTIC investigators. Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): an open-label, blinded-endpoint, randomised controlled superiority trial. Lancet. 2016 Oct 22;388(10055):2015-2022. doi: 10.1016/S0140-6736(16)31323-X. Epub 2016 Aug 28.
citation: Lozano I, Rumoroso JR, Perez de Prado A, Moreno R, Hernandez F. Antiplatelet Therapy After Stenting at the Crossroads: Easiest or Personalized Therapy? JACC Cardiovasc Interv. 2021 Apr 26;14(8):929-930. doi: 10.1016/j.jcin.2021.03.019. No abstract available.