VERONICA: VerifyNow to Optimise Platelet Inhibition in Coronary Acute Syndrome

Sponsor

Fundación EPIC (Other)

Overall Status

Recruiting

CT.gov ID

NCT04654052

Collaborator

(none)

634

Enrollment

Locations

Arms

Anticipated Duration (Months)

39.6

Patients Per Site

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objective of the study is to establish a de-scaling strategy of P2Y12 inhibitors (P2Y12

with a decrease in hemorrhagic events without increasing ischemic complications based on a Platelet Function Test (PFT).

Condition or Disease	Intervention/Treatment	Phase
Acute Coronary Syndrome Acute Myocardial Infarction Coronary Artery Disease Percutaneous Coronary Intervention	Drug: Clopidogrel Drug: Previous treatment	Phase 4

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

634 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 2, 2021

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Other: VerifyNow® PRUTest ≤30 (De-escalated Prasugrel Ticagrelor ) Patients with ACS on Prasugrel or Ticagrelor and PRU ≤ 30 at the end of the first month will be de-escalated to Clopidogrel 75 mg q.d during 11 months.	Drug: Clopidogrel Clopidogrel during 11 months
Other: VerifyNow® PRUTest ≤30 (Prasugrel or Ticagrelor ) Active comparator: Patients with ACS on Prasugrel or Ticagrelor and PRU ≤ 30 at the end of the first month will continue with these previous treatment during 11 months.	Drug: Previous treatment non-intervention

Arm

Intervention/Treatment

Other: VerifyNow® PRUTest ≤30 (De-escalated Prasugrel Ticagrelor )

Patients with ACS on Prasugrel or Ticagrelor and PRU ≤ 30 at the end of the first month will be de-escalated to Clopidogrel 75 mg q.d during 11 months.

Drug: Clopidogrel

Clopidogrel during 11 months

Other: VerifyNow® PRUTest ≤30 (Prasugrel or Ticagrelor )

Active comparator: Patients with ACS on Prasugrel or Ticagrelor and PRU ≤ 30 at the end of the first month will continue with these previous treatment during 11 months.

Drug: Previous treatment

non-intervention

Outcome Measures

Primary Outcome Measures

Incidence of Net Adverse Cardiac Events (NACE) [12 months]
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.

Secondary Outcome Measures

Incidence of Death (Cardiovascular) [12 months]
Death (Cardiovascular)
Incidence of Death [12 months]
Death
Incidence of Non fatal Myocardial Infarction (MI) [12 months]
Non fatal Myocardial Infarction
Incidence of Stroke [12 months]
Ischemic Stroke
Incidence of Thrombosis in target lesion [12 months]
Stent Thrombosis in target lesion
Incidence of revascularization on target lesion [12 months]
New revascularization on target lesion
Incidence of (BARC criteria ≥ 2) [12 months]
Bleeding (BARC criteria ≥ 2)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitario Virgen de La Arrixaca	El Palmar	Murcia	Spain	30120
2	Hospital General Universitario de Albacete	Albacete		Spain	02006
3	Hospital Del Mar	Barcelona		Spain	08003
4	Hospital Universitari Vall D Hebron	Barcelona		Spain	08035
5	Hospital San Pedro de Alcantara	Cáceres		Spain	10003
6	Hospital Universitario de Galdakao-Usansolo	Galdakao		Spain	48960
7	Hospital Universitario de Cabueñes	Gijón		Spain	33394
8	Hospital Universitario Virgen de Las Nieves	Granada		Spain	18014
9	Hospital Universitario Juan Ramon Jimenez	Huelva		Spain	21005
10	Hospital de León	León		Spain	24080
11	Hospital Universitario Lucus Agusti	Lugo		Spain	27003
12	Hospital Universitario de Salamanca	Salamanca		Spain	37007
13	Hospital Universitario Marques de Valdecilla	Santander		Spain	39008
14	Hospital Clinico Universitario de Valladolid	Valladolid		Spain	47003
15	Hospital Universitario Lozano Blesa	Zaragoza		Spain	50009
16	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009