VerifyNow to Optimise Platelet Inhibition in Coronary Acute Syndrome

Coronary Artery Disease Clinical Trial

— VERONICA  

Official title:

VerifyNow to Optimise Platelet Inhibition in Coronary Acute Syndrome (VERONICA Trial)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04654052
• Other study ID #: EPIC17- VERONICA
• Status: Recruiting
• Phase: Phase 4
• Start date: July 2, 2021
• Est. completion date: June 1, 2023

Study information

• Verified date: December 2022
• Source: Fundación EPIC
• Contact: Íñigo Lozano, MD, PhD
• Phone: +34630901145
• Email: inigo.lozano[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 634
• Est. completion date: June 1, 2023
• Est. primary completion date: June 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Acute Myocardial Infarction
• Coronary Artery Disease
• Infarction
• Myocardial Infarction
• Percutaneous Coronary Intervention
• Syndrome

Intervention

Drug:
• Clopidogrel
Clopidogrel during 11 months
• Previous treatment
non-intervention

Locations

Country	Name	City	State
Spain	Hospital General Universitario de Albacete	Albacete
Spain	Hospital Del Mar	Barcelona
Spain	Hospital Universitari Vall D Hebron	Barcelona
Spain	Hospital San Pedro de Alcantara	Cáceres
Spain	Hospital General Universitario de Ciudad Real	Ciudad Real
Spain	Hospital Universitario Virgen de La Arrixaca	El Palmar	Murcia
Spain	Hospital Universitario de Galdakao-Usansolo	Galdakao
Spain	Hospital Universitario de Cabueñes	Gijón
Spain	Hospital Universitario Virgen de Las Nieves	Granada
Spain	Hospital Universitari de Bellvitge	Hospitalet de Llobregat
Spain	Hospital Universitario Juan Ramon Jimenez	Huelva
Spain	Hospital de León	León
Spain	Hospital Universitario Lucus Agusti	Lugo
Spain	Hospital Universitario Regional de Malaga	Málaga
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital Clinico Universitario de Valladolid	Valladolid
Spain	Hospital Universitario Lozano Blesa	Zaragoza
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
Fundación EPIC

Country where clinical trial is conducted

Spain, 

References & Publications (7)

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. — View Citation

Cuisset T, Deharo P, Quilici J, Johnson TW, Deffarges S, Bassez C, Bonnet G, Fourcade L, Mouret JP, Lambert M, Verdier V, Morange PE, Alessi MC, Bonnet JL. Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study. Eur Heart J. 2017 Nov 1;38(41):3070-3078. doi: 10.1093/eurheartj/ehx175. — View Citation

Deharo P, Quilici J, Camoin-Jau L, Johnson TW, Bassez C, Bonnet G, Fernandez M, Ibrahim M, Suchon P, Verdier V, Fourcade L, Morange PE, Bonnet JL, Alessi MC, Cuisset T. Benefit of Switching Dual Antiplatelet Therapy After Acute Coronary Syndrome According to On-Treatment Platelet Reactivity: The TOPIC-VASP Pre-Specified Analysis of the TOPIC Randomized Study. JACC Cardiovasc Interv. 2017 Dec 26;10(24):2560-2570. doi: 10.1016/j.jcin.2017.08.044. — View Citation

Kerneis M, Silvain J, Abtan J, Cayla G, O'Connor SA, Barthelemy O, Vignalou JB, Beygui F, Brugier D, Martin R, Collet JP, Montalescot G. Switching acute coronary syndrome patients from prasugrel to clopidogrel. JACC Cardiovasc Interv. 2013 Feb;6(2):158-65. doi: 10.1016/j.jcin.2012.09.012. — View Citation

Kirtane AJ, Parikh PB, Stuckey TD, Xu K, Witzenbichler B, Weisz G, Rinaldi MJ, Neumann FJ, Metzger DC, Henry TD, Cox DA, Duffy PL, Brodie BR, Mazzaferri EL Jr, Parvataneni R, Maehara A, Genereux P, Mehran R, Stone GW. Is There an Ideal Level of Platelet P2Y12-Receptor Inhibition in Patients Undergoing Percutaneous Coronary Intervention?: "Window" Analysis From the ADAPT-DES Study (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents). JACC Cardiovasc Interv. 2015 Dec 28;8(15):1978-1987. doi: 10.1016/j.jcin.2015.08.032. — View Citation

Lozano I, Robles V, Vegas JM, Rondan J. De-Escalation of the P2Y12 Inhibitor After Acute Coronary Syndromes According to On-Treatment Platelet Reactivity: A Promising Step of Enormous Magnitude That Should Be Explored. JACC Cardiovasc Interv. 2018 Mar 12;11(5):507-508. doi: 10.1016/j.jcin.2018.01.246. No abstract available. — View Citation

Sibbing D, Aradi D, Jacobshagen C, Gross L, Trenk D, Geisler T, Orban M, Hadamitzky M, Merkely B, Kiss RG, Komocsi A, Dezsi CA, Holdt L, Felix SB, Parma R, Klopotowski M, Schwinger RHG, Rieber J, Huber K, Neumann FJ, Koltowski L, Mehilli J, Huczek Z, Massberg S; TROPICAL-ACS Investigators. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial. Lancet. 2017 Oct 14;390(10104):1747-1757. doi: 10.1016/S0140-6736(17)32155-4. Epub 2017 Aug 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Net Adverse Cardiac Events (NACE)	Net Adverse Cardiac Events, defined as a composite of: death from vascular causes (death from cardiovascular causes or cerebrovascular causes and any death without another known cause), non fatal MI, or non fatal stroke, Bleeding BARC type = 2.	12 months
Secondary	Incidence of Death (Cardiovascular)	Death (Cardiovascular)	12 months
Secondary	Incidence of Death	Death	12 months
Secondary	Incidence of Non fatal Myocardial Infarction (MI)	Non fatal Myocardial Infarction	12 months
Secondary	Incidence of Stroke	Ischemic Stroke	12 months
Secondary	Incidence of Thrombosis in target lesion	Stent Thrombosis in target lesion	12 months
Secondary	Incidence of revascularization on target lesion	New revascularization on target lesion	12 months
Secondary	Incidence of (BARC criteria = 2)	Bleeding (BARC criteria = 2)	12 months