Early reduction of antiplatelet therapy in patients with Acute Coronary Syndrome treated with stent implantation and at high risk of bleeding.

2023-509868-20-00 Protocol DESC-HBR Therapeutic confirmatory (Phase III) Ongoing, recruiting

Start 24 Jun 2023 · Status Ongoing, recruiting · 1 EU/EEA countries · 7 sites · Protocol DESC-HBR

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruiting
Participants planned 200
Countries 1
Sites 7

Acute coronary syndrome

The primary objective is to evaluate the pharmacodynamic effect of 3 different regimens of P2Y12 inhibitor de-escalation (prasugrel 5mg, ticagrelor 60mg/bid or clopidogrel 75mg) versus full-dose potent P2Y12 inhibitor (prasugrel 10mg or ticagrelor 90mg bid) on platelet reactivity, and to evaluate which treatment achiev…

Key facts

Sponsor
Azienda Ospedaliera Universitaria Gaetano Martino Messina, Azienda Ospedaliera Universitaria Gaetano Martino Messina
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Cardiovascular Diseases [C14]
Trial duration
24 Jun 2023 → ongoing
Decision date (initial)
2024-05-14
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
Italian Ministry of Health grant GR-2021-12374500 (Ricerca Finalizzata 2021)

External identifiers

EU CT number
2023-509868-20-00
EudraCT number
2023-000029-10
WHO UTN
U1111-1305-1319

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacodynamic

The primary objective is to evaluate the pharmacodynamic effect of 3 different regimens of P2Y12 inhibitor de-escalation (prasugrel 5mg, ticagrelor 60mg/bid or clopidogrel 75mg) versus full-dose potent P2Y12 inhibitor (prasugrel 10mg or ticagrelor 90mg bid) on platelet reactivity, and to evaluate which treatment achieves the highest proportion of patients in the optimal platelet reactivity (OPR) at treatment steady-state.

Secondary objectives 2

  1. The key secondary objective is to evaluate the clinical impact of P2Y12 inhibitor de-escalation versus full-dose potent P2Y12 inhibition on major, minor and nuisance bleeding according to the bleeding academic research consortium definition (BARC 1-5 bleeding) at 5 months after randomization.
  2. Other secondary objectives will be to evaluate ischemic and net clinical events and quality of life in the four treatment arms

Conditions and MedDRA coding

Acute coronary syndrome

VersionLevelCodeTermSystem organ class
20.0 PT 10051592 Acute coronary syndrome 100000004849

Study design 2 periods

#TitleAllocationBlindingRoles blindedArms
1 screening
Screening will be performed at the time of the index hospitalization for ACS or at early outpatient visit at 1 month (30 ±7 days). Potential patients will be informed about the study and asked for participation. Subjects will be enrolled after having signed and dated the informed consent form, if eligibility criteria are met and no exclusion criterion is present. A copy of the informed consent form with the patient’s information document will be given to the patient. Patients who have signed the informed consent form and meeting all inclusion and exclusion criteria will be included in the study. After inclusion patients will undergo the pre-randomization phase with point-of-care genetic testing and baseline platelet function testing through a buccal swab and blood sample respectively
 Not Applicable None
2 Baseline and randomization
The following evaluations will be performed at baseline: • Demographics; • Relevant medical history (general medical, cardiac, neurologic and renal history; cardiovascular history; risk factors (e.g. dyslipidemia, hypertension, diabetes mellitus, tobacco use, history of peripheral vascular disease, stroke, transient ischemic attack). • Ischemic/anginal status assessment (according to the Canadian Cardiovascular Society classification); • Current cardiovascular and diabetic medications; • Physical examination, including weight, height, arterial blood pressure and heart rate; • Recent routine laboratory tests, including complete blood count, blood chemistry (Na, K, creatinine, urea), glucose (HbA1c if patient with known diabetes), lipids (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides) and hemogram. • Electrocardiogram (ECG) • Transthoracic Echocardiogram After randomization, patients will receive the assigned randomized treatment and two hours after drug administration a blood sample will be drawn for platelet function testing. Patients will be instructed to the use of the ePRO for the recording of the daily intake of the study medication, and completion of the questionnaires.
 Randomised Controlled None control intervention: Full-dose potent P2Y12 inhibitor: the prescription of P2Y12 inhibitor assigned before study randomization including prasugrel 10mg qd or ticagrelor 90mg bid as previously prescribed will be continued.
Clopidogrel arm: In patients assigned to clopidogrel 75mg qd arm that were initially treated with prasugrel 10mg qd before randomization no loading dose of clopidogrel is needed and maintenance dose of clopidogrel 75mg qd will be started after randomization.
In patients assigned to clopidogrel 75mg qd arm that were initially treated with ticagrelor 90mg bid before randomization a loading dose of clopidogrel 600mg will be administered 24 hours after ticagrelor last dose and a maintenance dose of clopidogrel 75mg qd will be implemented from the day after.
Prasugrel arm: In patients assigned to prasugrel 5mg qd arm that were initially treated with prasugrel 10mg qd before randomization no loading dose of prasugrel is needed and maintenance dose of prasugrel 5mg qd will be started after randomization. In patients assigned to prasugrel 5mg qd arm that were initially treated with ticagrelor 90mg bid before randomization a loading dose of prasugrel 60mg will be administered 24 hours after ticagrelor last dose and a maintenance dose of prasugrel 5mg qd will be implemented from the day after.
Ticagrelor arm: In patients assigned to ticagrelor 60mg bid arm, irrespective of the prior assigned treatment with prasugrel 10mg or ticagrelor 90mg, no loading dose of ticagrelor is needed and maintenance dose of ticagrelor 60mg bid will be started after randomization.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

  1. - Informed Consent signed and dated.
  2. - 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)
  3. - 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.
  4. - Treated with DAPT with full-dose potent P2Y12 inhibitors (e.g. prasugrel 10mg or ticagrelor 90mg bid) according to international guidelines recommendations

Exclusion criteria 10

  1. Age < 18 years
  2. Known intolerance, hypersensitivity or contraindication (including active bleeding) to aspirin, clopidogrel, prasugrel, ticagrelor or to any of the excipients
  3. Indication to oral anticoagulation
  4. 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 etc.)
  5. Any planned major surgery or interventional procedure requiring treatment modification
  6. Prior transient ischemic attack, ischemic or haemorrhagic stroke
  7. Severe hepatic insufficiency (Child-Pugh class C)
  8. Ongoing therapy with strong CYP3A inducers or strong CYP3A inhibitors (e.g. ketoconazole, clarithromycin, nefazodone, ritonavir, atazanavir etc.)
  9. • 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
  10. • 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 non­compliance.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. The primary endpoint of the study is the incidence of optimal platelet reactivity (OPR) measured by means of the VerifyNow system (Accumetrics, San Diego, CA, USA), 2 hours after drug MD at 14±2 days from study inclusion. OPR will be defined as a PRU between 85 and 208 reactivity units according to international expert consensus

Secondary endpoints 7

  1. Key secondary endpoint of the study is the incidence of nuisance, minor or major bleeding according to the BARC definition (BARC 1-5).
  2. Platelet reactive units (PRU) at VerifyNow system before first randomized treatment administration (baseline), 2 hours after the first randomized treatment administration and before MD at 14±2 days from study inclusion.
  3. 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 pa
  4. 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
  5. 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.
  6. Cost-effectives analysis will be also carried out by inputting direct and indirect costs in relation to outcomes assessed.
  7. Other: Health mobility and mental scales (i.e. EQ-5D-5L, SF-12); Perceived stress (i.e. PPS); Modified Borg Dyspnoea Scale, non-adherence according to the non-adherence academic research consortium (NARC) scale

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Ticagrelor

SUB30898 · Substance

Active substance
Ticagrelor
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
120 mg milligram(s)
Max total dose
120 mg milligram(s)
Max treatment duration
6 Month(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Ticagrelor

SUB30898 · Substance

Active substance
Ticagrelor
Pharmaceutical form
FILM COATED TABLET
Route of administration
ORAL
Max daily dose
180 mg milligram(s)
Max total dose
180 mg milligram(s)
Max treatment duration
6 Month(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

CLOPIDOGREL DOC Generici 75 mg compresse rivestite con film

PRD303880 · Product

Active substance
Clopidogrel
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
75 mg milligram(s)
Max total dose
600 mg milligram(s)
Max treatment duration
6 Month(s)
Authorisation status
Authorised
ATC code
B01AC04 — CLOPIDOGREL
Marketing authorisation
039643010
MA holder
DOC GENERICI S.R.L.
MA country
Italy
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prasugrel Mylan 10 mg film-coated tablets

PRD9438918 · Product

Active substance
Prasugrel
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
10 mg milligram(s)
Max total dose
60 mg milligram(s)
Max treatment duration
6 Month(s)
Authorisation status
Authorised
ATC code
B01AC22 — -
Marketing authorisation
EU/1/18/1273/012
MA holder
MYLAN PHARMACEUTICALS LIMITED
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prasugrel

SUB30236 · Substance

Active substance
Prasugrel
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL USE
Max daily dose
60 mg milligram(s)
Max total dose
60 mg milligram(s)
Max treatment duration
6 Month(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Auxiliary 1

Acetylsalicylic Acid

SUB12730MIG · Substance

Active substance
Acetylsalicylic Acid
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL USE
Max daily dose
100 mg milligram(s)
Max total dose
100 mg milligram(s)
Max treatment duration
6 Month(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliera Universitaria Gaetano Martino Messina

Sponsor organisation
Azienda Ospedaliera Universitaria Gaetano Martino Messina
Address
Via Consolare Valeria N 1
City
Messina
Postcode
98124
Country
Italy

Scientific contact point

Organisation
Azienda Ospedaliera Universitaria Gaetano Martino Messina
Contact name
Francesco Costa

Public contact point

Organisation
Azienda Ospedaliera Universitaria Gaetano Martino Messina
Contact name
Paolo Liotta

Third parties 1

OrganisationCity, countryDuties
Mediolanum Cardio Research S.r.l.
ORG-100010094
 Milan, Italy Code 12, Data management, E-data capture, Code 8

Azienda Ospedaliera Universitaria Gaetano Martino Messina

Sponsor organisation
Azienda Ospedaliera Universitaria Gaetano Martino Messina
Address
Via Consolare Valeria N 1
City
Messina
Postcode
98124
Country
Italy

Scientific contact point

Organisation
Azienda Ospedaliera Universitaria Gaetano Martino Messina
Contact name
Francesco Costa

Public contact point

Organisation
Azienda Ospedaliera Universitaria Gaetano Martino Messina
Contact name
Paolo Liotta

Third parties 1

OrganisationCity, countryDuties
Mediolanum Cardio Research S.r.l.
ORG-100010094
 Milan, Italy Code 12, Data management, E-data capture, Code 8

Locations

1 EU/EEA country · 7 investigational sites

By country

CountryMS statusPlanned subjectsSites
Italy Ongoing, recruiting 200 7
Rest of world — 0 —

Investigational sites

Italy

7 sites · Ongoing, recruiting
Azienda Ospedaliera Universitaria Gaetano Martino Messina
UOC Cardiologia con Utic, Via Consolare Valeria N 1, 98124, Messina
ASST Grande Ospedale Metropolitano Niguarda
Cardiologia I Emodinamica, Piazza Dell'ospedale Maggiore 3, 20162, Milan
Azienda Sanitaria Locale To3
S,C. Cardiologia, Via Rivalta 29, 10098, Rivoli
Azienda Ospedaliero Universitaria Policlinico G Rodolico San Marco Di Catania
Unità di Cardiologia, Via Santa Sofia 78, 95123, Catania
IRCCS Ospedale Policlinico San Martino
UOSD Cardiologia Interventistica, Largo Rosanna Benzi 10, 16132, Genoa
Gvm Hospitals Of Care And Research
Cardiologia, Via Corriera 1, 48033, Cotignola
Azienda Ospedaliera Ordine Mauriziano Di Torino
S.C. Cardiololgia, Via Ferdinando Magellano 1, 10128, Turin

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Italy 2023-06-24 2023-06-24

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-03-16 Italy Acceptable
2024-05-09
 2024-05-14

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