Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen

Coronary Artery Disease Clinical Trial

— MASTER DAPT  

Official title:

Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03023020
• Other study ID #: ECRI-009
• Status: Completed
• Phase: N/A
• Start date: April 4, 2017
• Est. completion date: April 30, 2021

Study information

• Verified date: August 2021
• Source: ECRI bv
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study compares two lengths of medication therapy (a shortened versus a prolonged dual antiplatelet therapy) in order to prevent thrombus (blood cloth) formation after the successfully treatment for coronary heart disease with a drug covered stent (metallic tube).

This comparison will be done in patients who, compared to the average patient, are more likely to suffer from complications on antiplatelet therapy (bleeding). Both durations are within the current medical recommendations. The aim of this study is to help improve further standard antiplatelet duration guidelines.

Description:

The study objective is to determine in a high bleeding risk patient population undergoing PCI under standardized treatment (within current guidelines and instructions for use and including the bioresorbable polymer coated Ultimaster sirolimus-eluting stent), whether abbreviated DAPT is non-inferior to prolonged DAPT regimen in terms of NACE within 12 months, whether abbreviated DAPT is non-inferior to prolonged DAPT regimen in terms of MACCE within 12 months and whether abbreviated DAPT is superior to prolonged DAPT regimen in terms of MCB within 12 months.

There are two treatment strategies:

• abbreviated dual anti-platelet therapy: dual antiplatelet therapy is discontinued and a single antiplatelet agent is continued until at least 11 months post randomization (i.e. 12 months post stent implantation). In patients on oral anticoagulants, dual antiplatelet therapy is discontinued and either Aspirin or Clopidogrel is continued until 5 months post randomization (i.e. 6 months post stent implantation). Oral anticoagulation is continued until at least 11 months post randomization (i.e. 12 months post stent implantation) OR

• prolonged dual anti-platelet therapy: aspirin is continued for at least 11 months post randomization (i.e. 12 months post stent implantation), the P2Y12 inhibitor being taken at the time of randomization is continued for at least 5 months and up to 11 months post randomization (i.e. 12 months post stent implantation). In patients on oral anticoagulants, aspirin and Clopidogrel are continued for at least 2 months post randomization (i.e. 3 months post stent implantation) and up to 11 months post randomization (i.e. 12 months after stent implantation). Therefore either aspirin or Clopidogrel is continued up to 11 months post randomization (i.e. 12 months post stent implantation)

The study design is an investigator-initiated, randomized, multi-center, clinical trial to be conducted in approximately 100 interventional cardiology centers in across the globe excluding USA. The study includes 2 x 2150 patients (i.e. 4300 patients) Randomization will occur at one month after the PCI procedure. The expected duration of participation for each patient is 14 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4579
• Est. completion date: April 30, 2021
• Est. primary completion date: April 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

After index PCI, patients aged 18 years or more are eligible for inclusion into the study if the following criteria are met.

1. At least one among the HBR criteria (as defined below) is met.

2. All lesions are successfully treated with Ultimaster stent in the context of routine clinical care, i.e. post-procedural angiographic diameter stenosis <20% by visual estimation

3. Free from any flow-limiting angiographic complications (i.e. significant untreated dissection or major side-branch occlusion), which require prolonged DAPT duration based on operator's opinion.

4. All stages of PCI are complete (if any) and no further PCI is planned.

At randomization visit (one month after index PCI), the following criteria must be met:

1. Fulfilment of at least one HBR criterion (as defined below), or on the basis of post-PCI actionable (i.e. requiring medical attention) non-access site related bleeding episode

2. Uneventful 30-day clinical course, i.e. free from spontaneous MI, symptomatic restenosis, stent thrombosis, stroke and any revascularization (coronary and non-coronary) requiring prolonged DAPT

3. If not on OAC,

1. Patient is on a DAPT regimen of aspirin and a P2Y12 inhibitor

2. Patient with one type of P2Y12 inhibitor for at least 7 days (i.e. no switching between oral P2Y12 inhibitors has occurred in the previous 7 days)

4. If on OAC

1. Patient is on the same type of OAC (e.g. Vitamin K antagonist or NOAC) for at least 7 days

2. Patient is on clopidogrel for at least 7 days

Definition of HBR

Post-PCI patients are at HBR if at least one of the following criteria applies:

• Clinical indication for treatment with oral anticoagulants (OAC) for at least 12 months

• Recent (<12 months) non-access site bleeding episode(s), which required medical attention (i.e. actionable bleeding).

• Previous bleeding episode(s) which required hospitalization if the underlying cause has not been definitively treated (i.e. surgical removal of the bleeding source)

• Age equal or greater than 75 years

• Systemic conditions associated with an increased bleeding risk (e.g. haematological disorders, including a history of or current thrombocytopaenia defined as a platelet count <100,000/mm3 (<100 x 109/L), or any known coagulation disorder associated with increased bleeding risk.

• Documented anaemia defined as repeated haemoglobin levels <11 g/dl or transfusion within 4 weeks before randomization.

• Need for chronic treatment with steroids or non-steroidal anti-inflammatory drugs

• Diagnosed malignancy (other than skin) considered at high bleeding risk including gastro-intestinal, genito-urethral/renal and pulmonary.

• Stroke at any time or TIA in the previous 6 months

• PRECISE DAPT score of 25 or greater

Exclusion Criteria:

1. Treated with stents other than Ultimaster stent within 6 months prior to index procedure

2. Treated for in-stent restenosis or stent thrombosis at index PCI or within 6 months before

3. Treated with a bioresorbable scaffold at any time prior to index procedure

4. Cannot provide written informed consent

5. Under judicial protection, tutorship or curatorship

6. Unable to understand and follow study-related instructions or unable to comply with study protocol

7. Active bleeding requiring medical attention (BARC=2) on randomization visit

8. Life expectancy less than one year

9. Known hypersensitivity or allergy for aspirin, clopidogrel, ticagrelor, prasugrel, cobalt chromium or sirolimus

10. Any planned and anticipated PCI

11. Participation in another trial

12. Pregnant or breast feeding women

Related Conditions & MeSH terms

• Coronary Artery Disease
• Hemorrhage
• High Bleeding Risk
• PCI

Intervention

Drug:
• Aspirin
Dosing per current guidelines and local practice
• P2Y12 inhibitor
Dosing per current guidelines and local practice

Locations

Country	Name	City	State
Argentina	Buenos Aires Research center	Buenos Aires
Argentina	Interventional Cardiology Sanatorio	Buenos Aires
Australia	The Prince Charles Hospital	Chermside
Australia	St Vincents Hospital Melbourne	Melbourne
Australia	Research Center Perth	Perth
Australia	Research Center Sydney	Sydney
Australia	Wollongong Research Center	Wollongong
Austria	Research Center , 043-02	Wien
Austria	Research Center, 043-01	Wien
Bahrain	Research Centre Manama	Manama
Bangladesh	Dhaka Research Center	Dhaka
Belgium	Research Center Aalst	Aalst
Belgium	Research Center Bonheiden	Bonheiden
Belgium	CHU st.Pierre	Bruxelles
Belgium	Research Centre Charleroi	Charleroi
Belgium	Research Center Hasselt	Hasselt
Belgium	Research Centre Liège	Liège
Bulgaria	MHAT Sveta Karidad Plovdiv	Plovdiv
Bulgaria	Sofia Resaerch Center, 359-02	Sofia
Bulgaria	Sofia Research Center, 359-01	Sofia
Bulgaria	Sofia Research Center, 359-03	Sofia
Czechia	Research Center Brno	Brno
Czechia	Research Center Phraha	Praha
Denmark	Research Center Roskilde	Roskilde
Estonia	Research Center Tallinn	Tallinn
France	Research Center Annecy	Annecy
France	Hospital Prive Saint Martin	Caen
France	Research Centre Caen	Caen
France	Research Centre Créteil	Créteil
France	Research Center Dijon	Dijon
France	Hopital de la Timone	Marseille
France	Research Center Massy	Massy
France	Hospital de Mercy	Metz
France	Research Center Montauban	Montauban
France	Research Centre Montpellier	Montpellier
France	Research Center Nantes	Nantes
France	CHU Nimes	Nîmes
France	Research Center Paris, 033-05	Paris
France	Research Center Paris, 033-06	Paris
France	Research Centre Rouen	Rouen
France	Research Center Saint-Denis	Saint-Denis
Germany	Saarland University	Homburg
Germany	Cardiology Clinic	Landshut
Hungary	Research Centre Budapest	Budapest
Hungary	Research Center Szeged	Szeged
India	Research Center Chennai, 091-01	Chennai
India	Research Center Chennai, 091-05	Chennai
India	Research Center Coimbatore	Coimbatore
India	Research Center Surat	Surat
Israel	Research Center Haifa	Haifa
Israel	Research Center Jerusalem	Jerusalem
Israel	Rabin MC	Petah tikva
Israel	Research Center Safed	Safed
Italy	Ospedale Lorenzo Bonomo	Andria
Italy	Azienda Ospedaliera Brotzu	Cagliari
Italy	Second university of Naples Monaldi Hospital	Caserta
Italy	Research Center Catania	Catania
Italy	AOU Policlinico Gaetano Martino	Messina
Italy	Niguarda	Milan
Italy	Research Center Milan, 039-01	Milan
Italy	Research Center Milan, 039-04	Milan
Italy	Research Center Milan, 039-11	Milan
Italy	San Donato Hospital	Milan
Italy	Ospedale Sandro Pertini	Roma
Italy	Policlinico Casilino	Rome
Italy	Policlinico Umberto I	Rome
Italy	Research Center Rozzano	Rozzano
Italy	Clinic Cardiology	Treviglio
Italy	Research Center Vimercate	Vimercate
Japan	Kokura Memorial Hospital	Fukuoka
Japan	Research Center Gifu	Gifu
Japan	Ichinomiya Municipal Hospital	Ichinomiya
Japan	St.Marianna University School of Medicine	Kawasaki
Japan	Aichi Medical University Hospital	Nagakute
Japan	Japan Red Cross Nagoya Daiichi Hospital (1st)	Nagoya
Japan	Japan Red Cross Nagoya Daini Hospital (2nd)	Nagoya
Japan	Nagoya University Hospital	Nagoya
Japan	Osaka police Hospital	Osaka
Japan	St.Luke's International Hospital	Tokyo
Japan	Research Center Toyoake	Toyoake
Korea, Republic of	Research Center Seoul	Seoul
Netherlands	Research Center Den Bosch	's Hertogenbosch
Netherlands	Research Centre Arnhem	Arnhem
Netherlands	Research Center Breda	Breda
Netherlands	Research Centre Dordrecht	Dordrecht
Netherlands	Research Centre Eindhoven	Eindhoven
Netherlands	Research Center Emmen	Emmen
Netherlands	Research Centre Enschede	Enschede
Netherlands	Antonius ziekenhuis	Nieuwegein
Netherlands	Research Center Rotterdam	Rotterdam
Netherlands	Research Centre Terneuzen	Terneuzen
Netherlands	Haga Hospital	The Hague
North Macedonia	Research Center Skopje	Skopje
Poland	University Hospital Krakow	Krakow
Poland	Research Center Krakow	Kraków
Poland	Miedziowe Centrum Zdrowia SA	Lubin
Poland	Research Center Poznan	Poznan
Poland	Research Centre Wroclaw	Wroclaw
Saudi Arabia	Research Center Jeddah	Jeddah
Saudi Arabia	Research Center Riyadh	Riyadh
Serbia	Researcg Center Belgrade, 381-02	Belgrade
Serbia	Research Center of Serbia, 381-01	Belgrade
Serbia	Research Center Sremska Kamenica	Sremska Kamenica
Singapore	Singapore Research Center	Singapore
Singapore	Tan Tock Seng Hospital	Singapore
Slovenia	Ljubljana Research Center	Ljubljana
Spain	Research Center Alicante	Alicante
Spain	Research Center Barcelona, 034-07	Barcelona
Spain	Research Center Barcelona, 034-09	Barcelona
Spain	Universitario Virgen de la Arrixaca	El Palmar
Spain	Research Center Huelva	Huelva
Spain	Hospital Universitario Puerta de hierro	Madrid
Spain	Research Center Madrid, 034-06	Madrid
Spain	Research Center Madrid, 034-10	Madrid
Spain	Hospital Universitario Valdecilla	Santander
Spain	Research Center Vigo	Vigo
Sweden	Research Center Gavle	Gävle
Sweden	Research Center Orebro	Örebro
Switzerland	Lindenhofspital	Bern
Switzerland	Research Centre Bern	Bern
Switzerland	Research Centre Fribourg	Fribourg
Switzerland	University Hospital Geneva	Geneva
Switzerland	Research Centre Liestal	Liestal
Switzerland	Research Centre Lugano	Lugano
Switzerland	Research Centre Zürich	Zürich
United Kingdom	Research Center Blackburn	Blackburn
United Kingdom	Research Center Bournemouth	Bournemouth
United Kingdom	Research Centre Brighton	Brighton
United Kingdom	Bristol Heart Institute	Bristol
United Kingdom	Altnagelvin Hospital	Derry
United Kingdom	St George's Hospital	London
United Kingdom	Manchester Research Center	Manchester
United Kingdom	Research Center Newcastle	Newcastle Upon Tyne
United Kingdom	Research Center Stevenage	Stevenage
United Kingdom	Research Centre Stoke-on-Trent	Stoke-on-Trent
United Kingdom	Research Centre Wolverhampton	Wolverhampton
United Kingdom	Research Centre Worcester	Worcester
Vietnam	Vietnam National Heart Institute	Hanoi

Sponsors (5)

Lead Sponsor	Collaborator
ECRI bv	Cardialysis B.V., European Cardiovascular Research Center, Terumo Medical Corporation, University of Bern

Countries where clinical trial is conducted

Argentina,  Australia,  Austria,  Bahrain,  Bangladesh,  Belgium,  Bulgaria,  Czechia,  Denmark,  Estonia,  France,  Germany,  Hungary,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  North Macedonia,  Poland,  Saudi Arabia,  Serbia,  Singapore,  Slovenia,  Spain,  Sweden,  Switzerland,  United Kingdom,  Vietnam, 

References & Publications (3)

Authors/Task Force members, Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Jüni P, Kappetein AP, Kastrati A, Knuuti J, Landmesser U, Laufer G, Neumann FJ, Richter DJ, Schauerte P, Sousa Uva M, Stefanini GG, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014 Oct 1;35(37):2541-619. doi: 10.1093/eurheartj/ehu278. Epub 2014 Aug 29. — View Citation

Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, Granger CB, Lange RA, Mack MJ, Mauri L, Mehran R, Mukherjee D, Newby LK, O'Gara PT, Sabatine MS, Smith PK, Smith SC, Jr. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. Circulation 2016

Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, Bax JJ, Borger MA, Brotons C, Chew DP, Gencer B, Hasenfuss G, Kjeldsen K, Lancellotti P, Landmesser U, Mehilli J, Mukherjee D, Storey RF, Windecker S; ESC Scientific Document Group . 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016 Jan 14;37(3):267-315. doi: 10.1093/eurheartj/ehv320. Epub 2015 Aug 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Net adverse clinical endpoints (NACE) defined as a composite of all-cause death, myocardial infarction, stroke and bleeding events defined as BARC 3 or 5		11 months
Primary	Major adverse cardiac and cerebral events (MACCE) defined as a composite of all-cause death, myocardial infarction and stroke		11 months
Primary	Major or clinically relevant non-major bleeding (MCB) defined as a composite of type 2, 3 and 5 BARC bleeding events		11 months
Secondary	All cause death		14 months
Secondary	Death from cardiovascular causes		14 months
Secondary	Myocardial infarction		14 months
Secondary	Stroke		14 months
Secondary	Bleeding events		14 months
Secondary	Definite or probable stent thrombosis		14 months
Secondary	Any target vessel revascularization		14 months
Secondary	Urgent target vessel revascularization		14 months
Secondary	Urgent non-target vessel revascularization		14 months
Secondary	Clinically indicated non-target vessel revascularization		14 months
Secondary	Transfusion rates both in patients with and/or without clinically detected over bleeding		14 months