- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05903976
De-escalating Antiplatelet Therapy to Assess Platelet Reactivity and Outcomes in High Bleeding Risk Patients With Recent ACS (DESC-HBR)
August 22, 2023 updated by: Azienda Ospedaliera Universitaria Policlinico "G. Martino"
De-Escalation of Antiplatelet Therapy to Evaluate Platelet Reactivity and Clinical Outcomes After Coronary Stenting in Patients at High Bleeding Risk and Recent Acute Coronary Syndrome: DESC-HBR Trial
High bleeding risk (HBR) patients, comprising up to 50% of those presenting with acute coronary syndrome (ACS), are a high-risk group that is increasing in size due to an aging population.
The optimal selection of the potency and duration of antiplatelet therapy to reduce the risk of recurrent ischemic and bleeding events in HBR patients is still a matter of debate.
Multiple strategies to reduce bleeding during secondary prevention, such as reducing the duration of dual antiplatelet therapy, using single antiplatelet therapy with a P2Y12 inhibitor, or de-escalating to a lower potency or lower-dose P2Y12 inhibitor, have been proposed.
De-escalation to a lower potency or lower-dose P2Y12 inhibitor is particularly attractive because it maintains efficient pharmacological inhibition of multiple platelet pathways while potentially reducing bleeding through less aggressive activity.
Yet, there has been no study comparing the effects of different de-escalation strategies with the standard potent P2Y12 inhibitors in HBR patients.
The aim of the DESC-HBR study is to assess the impact of de-escalating P2Y12 inhibitor to clopidogrel 75mg, prasugrel 5mg or ticagrelor 60mg bid in HBR patients, in comparison with full-dose potent P2Y12 inhibitors, on the proportion of patients with optimal platelet reactivity (OPR).
Secondary objectives involve exploring the effect of de-escalation on clinical events and patients' quality of life.
Study Overview
Status
Recruiting
Intervention / Treatment
Detailed Description
The aim of the DESC-HBR trial is to compare the impact of de-escalating P2Y12 inhibitor to clopidogrel 75mg, prasugrel 5mg or ticagrelor 60mg bid, with full-dose potent P2Y12 inhibitors, on the proportion of patients with optimal platelet reactivity (OPR).
The secondary objective is to explore the effect of de-escalating P2Y12 inhibitor therapy on clinical events and patients' quality of life.
The primary outcome is the proportion of patients in the OPR range measured through the VerifyNow system at peak level after drug maintenance dose (MD) at 14±2 days.
OPR is defined as a platelet reactive unit (PRU) between 85 and 208 reactivity units based on international consensus.
A key secondary outcome will be major, minor and nuisance bleeding according to the bleeding academic research consortium (BARC) definition up to 5 months.
Secondary pharmacodynamic outcomes include platelet reactivity with the VerifyNow and T-TAS system at different timepoints (baseline, 2h after first dose, through levels before MD and peak levels after MD at 14±2 days).
Further pharmacodynamic assessment at 1 and 2 weeks after P2Y12 inhibitor discontinuation will be performed in the subset of patients discontinuing P2Y12 inhibitor at study conclusion or in case of P2Y12 discontinuation at anytime during the study.Other secondary endpoints will be explored including all-cause death, major adverse cardiac and cerebrovascular events (MACCE), a composite of cardiac death, myocardial infarction (MI), target vessel revascularization (TVR) and stroke, net adverse clinical events (NACE), a composite of MACCE and BARC 2-5 bleeding, and each individual endpoint singularly appraised.
Quality of life will be evaluated with health mobility and performance scales (i.e.
EQ-5D-5L, SF-12), perceived stress scale (i.e.
PPS).Cost-effectives analysis will be also carried out by inputting direct and indirect costs in relation to outcomes.
Study visits are scheduled at baseline,14±2 days, 3 and 5 months after randomization.
Study Type
Interventional
Enrollment (Estimated)
200
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Francesco Costa, MD, PhD
- Phone Number: 2341 +39090221
- Email: francesco.costa@unime.it
Study Locations
-
-
-
Messina, Italy, 98125
- Recruiting
- Azienda Ospedaliera Universitaria Gaetano Martino
-
Contact:
- Francesco Costa, MD, PhD
-
Principal Investigator:
- Francesco Costa, MD, PhD
-
Rivoli, Italy, 10098
- Not yet recruiting
- Ospedale Degli Infermi
-
Contact:
- Greca Zanda, MD
-
Principal Investigator:
- Giorgio Quadri, MD
-
Principal Investigator:
- Greca Zanda, MD
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Description
Participants fulfilling all the following inclusion criteria are eligible for the study:
- Informed Consent signed and dated.
- Patients deemed at HBR according to standard definitions (i.e. PRECISE-DAPT ≥25 or HBR-ARC with at least 1 major or 2 minor criteria).
- Treated with PCI due to a recent ACS (i.e. unstable angina, non-ST segment elevated myocardial infarction or ST segment elevated myocardial infarction) 30 ±7 days earlier.
- Treated with DAPT with full-dose potent P2Y12 inhibitors (e.g. prasugrel 10mg or ticagrelor 90mg bid) according to international guidelines recommendations.
The presence of anyone of the following exclusion criteria will lead to exclusion of the participant:
- Age < 18 years
- Known intolerance, hypersensitivity or contraindication (including active bleeding) to aspirin, clopidogrel, prasugrel, ticagrelor or to any of the excipients
- Indication to oral anticoagulation
- Indication to prolonged treatment with full-dose potent P2Y12 inhibitors (e.g. previous stent thrombosis, stenting of last remaining vessel, stent with indication for longer-term DAPT, perceived very high coronary ischemic risk)
- Any planned major surgery or interventional procedure requiring treatment modification
- Prior transient ischemic attack, ischemic or haemorrhagic stroke
- Severe hepatic insufficiency (Child-Pugh class C)
- Ongoing therapy with strong CYP3A inducers or strong CYP3A inhibitors (e.g. ketoconazole, clarithromycin, nefazodone, ritonavir, atazanavir etc.)
- Women who are pregnant, breast feeding or of childbearing potential (i.e. fertile, following menarche and who are not surgically sterile, including hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or post-menopausal defined as no menses for 12 months without an alternative medical cause); Participation in another study with investigational drug within the 30 days, or 5 half-lives of the study drug whichever is longer, preceding and during the present study
- Enrolment of the investigator, his/her family members, employees
- Inability to follow the procedures of the study (language problems, mental disorders, dementia) or comorbidities associated with less than 12 months-life expectation (active malignancies drug or alcohol abuse, etc.) or other conditions that might result in protocol non-compliance.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: CLOPIDOGREL 75 mg qd
50 patients treated with clopidogrel 75mg
|
Comparing, in patients at High Bleeding Risk (HBR) after a recent Acute Coronary Syndrome (ACS), continuation of full-dose potent P2Y12 inhibitor with a P2Y12i de-escalation strategy transitioning to clopidogrel 75mg, prasugrel 5mg or ticagrelor 60mg/bid.
|
Experimental: PRASUGREL 5mg qd
50 patients treated with prasugrel 5mg
|
Comparing, in patients at High Bleeding Risk (HBR) after a recent Acute Coronary Syndrome (ACS), continuation of full-dose potent P2Y12 inhibitor with a P2Y12i de-escalation strategy transitioning to clopidogrel 75mg, prasugrel 5mg or ticagrelor 60mg/bid.
|
Experimental: TICAGRELOR 60mg bid
50 patients treated with ticagrelor 60mg bid
|
Comparing, in patients at High Bleeding Risk (HBR) after a recent Acute Coronary Syndrome (ACS), continuation of full-dose potent P2Y12 inhibitor with a P2Y12i de-escalation strategy transitioning to clopidogrel 75mg, prasugrel 5mg or ticagrelor 60mg/bid.
|
Active Comparator: Continue Potent P2Y12i Full-Dose
50 patients in the full-dose potent P2Y12 inhibitor (prasugrel 10 mg or ticagrelor 90 mg bid according to prior prescription)
|
Comparing, in patients at High Bleeding Risk (HBR) after a recent Acute Coronary Syndrome (ACS), continuation of full-dose potent P2Y12 inhibitor with a P2Y12i de-escalation strategy transitioning to clopidogrel 75mg, prasugrel 5mg or ticagrelor 60mg/bid.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of Patients Achieving Optimal Platelet Reactivity (OPR) at peak level following Drug Maintenance Dose (MD) Using the VerifyNow System
Time Frame: 2 hours after drug MD at 14±2 days from study inclusion
|
The incidence of optimal platelet reactivity (OPR) measured by means of the VerifyNow system.
OPR will be defined as a PRU between 85 and 208 reactivity units according to international expert consensus.
|
2 hours after drug MD at 14±2 days from study inclusion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Bleeding Events According to Multiple Bleeding Definitions
Time Frame: 5 Months after enrollment
|
The incidence of nuisance, minor or major bleeding according to the BARC definition (BARC 1-5).
|
5 Months after enrollment
|
Platelet reactive units (PRU) at VerifyNow system
Time Frame: baseline, 2 hours after the first treatment administration and before MD at 14±2 days from study inclusion
|
Platelet reactive units (PRU) measurement at VerifyNow system
|
baseline, 2 hours after the first treatment administration and before MD at 14±2 days from study inclusion
|
Proportion of high platelet reactivity (HPR) and the proportion of low platelet reactivity (LPR) measured through the VerifyNow system
Time Frame: baseline, 2 hours after the first treatment administration, before MD at 14±2 days from study inclusion and at 2 hours after drug MD administration at 14±2 days
|
The proportion of high platelet reactivity (HPR) defined as PRU > 208, and the proportion of low platelet reactivity (LPR), defined as PRU < 85, measured through the VerifyNow system before first randomized treatment administration (baseline), 2 hours after the first randomized treatment administration, before MD at 14±2 days from study inclusion and at 2 hours after drug MD administration at 14±2 days from study inclusion.
PRU at 1 and 2 weeks after P2Y12 inhibitor discontinuation study in patients permanently ceasing treatment.
|
baseline, 2 hours after the first treatment administration, before MD at 14±2 days from study inclusion and at 2 hours after drug MD administration at 14±2 days
|
Platelet-derived thrombogenicity at Total Thrombus Formation (T-TAS)
Time Frame: baseline, 2 hours after the first treatment administration, before and after MD at 14±2 days from study inclusion.
|
Platelet-derived thrombogenicity at Total Thrombus Formation (T-TAS) before first randomized treatment administration (baseline), 2 hours after the first randomized treatment administration, before and after MD at 14±2 days from study inclusion.
|
baseline, 2 hours after the first treatment administration, before and after MD at 14±2 days from study inclusion.
|
Adverse clinical event
Time Frame: 14±2 days, 3 and 5 months from study inclusion
|
Adverse clinical events, assessed at each visit and up to 5 months after randomization.
They include: death, cardiac death, non-fatal myocardial infarction, non-fatal stroke, urgent target vessel revascularization, definite/probable stent thrombosis and net adverse clinical events.
|
14±2 days, 3 and 5 months from study inclusion
|
Cost-effectiveness
Time Frame: 5 Months after enrollment
|
Cost-effectives analysis will be carried out by inputting direct and indirect costs in relation to outcomes assessed.
|
5 Months after enrollment
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 12, 2023
Primary Completion (Estimated)
June 30, 2025
Study Completion (Estimated)
October 30, 2025
Study Registration Dates
First Submitted
May 26, 2023
First Submitted That Met QC Criteria
June 12, 2023
First Posted (Actual)
June 15, 2023
Study Record Updates
Last Update Posted (Actual)
August 23, 2023
Last Update Submitted That Met QC Criteria
August 22, 2023
Last Verified
August 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- DESC-HBR
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Coronary Artery Disease
-
Elixir Medical CorporationIstituto Clinico HumanitasActive, not recruitingCoronary Artery Disease | Chronic Total Occlusion of Coronary Artery | Multi Vessel Coronary Artery Disease | Bifurcation of Coronary Artery | Long Lesions Coronary Artery DiseaseItaly
-
Fundación EPICActive, not recruitingCoronary Artery Disease | Left Main Coronary Artery Disease | Left Main Coronary Artery Stenosis | Restenosis, CoronarySpain
-
Peking Union Medical College HospitalNot yet recruitingCoronary Artery Disease | Inflammation | Coronary Artery Disease Progression | Coronary Artery Stenosis | Coronary Artery Restenosis | Inflammatory Disease | Inflammation VascularChina
-
Peking Union Medical College HospitalRecruitingCoronary Artery Disease | Inflammation | Coronary Artery Disease Progression | Coronary Artery Stenosis | Coronary Artery Restenosis | Inflammatory Disease | Inflammation VascularChina
-
IGLESIAS Juan FernandoUniversity of BernNot yet recruiting
-
National Institutes of Health Clinical Center (CC)National Heart, Lung, and Blood Institute (NHLBI)CompletedCoronary Arteriosclerosis | Coronary Artery Disease (CAD) | Obstructive Coronary Artery DiseaseUnited States
-
Barts & The London NHS TrustImperial College London; Brunel UniversityNot yet recruitingCORONARY ARTERY DISEASE
-
Fundación EPICRecruitingCoronary Artery Disease | Coronary Disease | Coronary Occlusion | Left Main Coronary Artery Disease | Coronary Artery StenosisSpain
-
Abbott Medical DevicesCompletedCoronary Artery Disease | Coronary Disease | Coronary Occlusion | Chronic Total Occlusion of Coronary Artery | Coronary Restenosis | Coronary Artery Stenosis | Coronary Artery RestenosisBelgium
-
China National Center for Cardiovascular DiseasesRecruitingLeft Main Coronary Artery DiseaseChina
Clinical Trials on P2Y12 inhibitor de-escalation
-
Universitaire Ziekenhuizen KU LeuvenKU Leuven; Stichting tegen KankerRecruitingSquamous Cell Carcinoma of Head and NeckBelgium
-
Region SkaneExact Sciences CorporationRecruiting
-
British Columbia Cancer AgencyCompletedEndometrial CancerCanada
-
University Medical Centre MariborCompletedAggression | Education | Physical RestraintSlovenia
-
Bergen University CollegeHelse-Bergen HFCompleted
-
Royal North Shore HospitalNot yet recruitingHPV Positive Oropharyngeal Squamous Cell CarcinomaAustralia
-
Technische Universität DresdenGerman Cancer Research Center; National Center for Tumor Diseases, Heidelberg; Radiation Oncology Working Group of the German Cancer Society and other collaboratorsRecruitingHead-and-neck Squamous Cell CarcinomaGermany
-
National Cancer Institute, EgyptRecruitingHead and Neck CarcinomaEgypt
-
Universitaire Ziekenhuizen KU LeuvenUniversity Hospital, GhentCompleted
-
Seoul National University HospitalLudwig-Maximilians - University of Munich; ST. Antonius hospital NieuwegeinRecruitingCoronary Artery Disease | Acute Coronary SyndromeKorea, Republic of