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

Sponsor

ECRI bv (Industry)

Overall Status

Completed

CT.gov ID

NCT03023020

Collaborator

Cardialysis B.V. (Industry), European Cardiovascular Research Center (Other), University of Bern (Other), Terumo Medical Corporation (Industry)

4,579

Enrollment

138

Locations

Arms

48.9

Actual Duration (Months)

33.2

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
High Bleeding Risk Coronary Artery Disease PCI	Drug: Aspirin Drug: P2Y12 inhibitor	N/A

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

4579 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 4, 2017

Actual Primary Completion Date :

Apr 30, 2021

Actual Study Completion Date :

Apr 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Other: Abbreviated antiplatelet regimen Dual antiplatelet therapy is discontinued immediately after randomization (i.e. 1 month post stent implantation), 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 immediately after randomization (i.e. 1 month post stent implantation), 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)	Drug: Aspirin Dosing per current guidelines and local practice Other Names: antiplatelet agent Drug: P2Y12 inhibitor Dosing per current guidelines and local practice Other Names: antiplatelet agent
Other: Prolonged antiplatelet regimen 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). Either aspirin or Clopidogrel is continued up to 11 months post randomization (i.e. 12 months post stent implantation)	Drug: Aspirin Dosing per current guidelines and local practice Other Names: antiplatelet agent Drug: P2Y12 inhibitor Dosing per current guidelines and local practice Other Names: antiplatelet agent

Arm

Intervention/Treatment

Other: Abbreviated antiplatelet regimen

Dual antiplatelet therapy is discontinued immediately after randomization (i.e. 1 month post stent implantation), 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 immediately after randomization (i.e. 1 month post stent implantation), 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)

Drug: Aspirin

Dosing per current guidelines and local practice

Other Names:

antiplatelet agent

Drug: P2Y12 inhibitor

Dosing per current guidelines and local practice

Other Names:

antiplatelet agent

Other: Prolonged antiplatelet regimen

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). Either aspirin or Clopidogrel is continued up to 11 months post randomization (i.e. 12 months post stent implantation)

Drug: Aspirin

Dosing per current guidelines and local practice

Other Names:

antiplatelet agent

Drug: P2Y12 inhibitor

Dosing per current guidelines and local practice

Other Names:

antiplatelet agent

Outcome Measures

Primary Outcome Measures

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]
Major adverse cardiac and cerebral events (MACCE) defined as a composite of all-cause death, myocardial infarction and stroke [11 months]
Major or clinically relevant non-major bleeding (MCB) defined as a composite of type 2, 3 and 5 BARC bleeding events [11 months]

Secondary Outcome Measures

All cause death [14 months]
Death from cardiovascular causes [14 months]
Myocardial infarction [14 months]
Stroke [14 months]
Bleeding events [14 months]
Definite or probable stent thrombosis [14 months]
Any target vessel revascularization [14 months]
Urgent target vessel revascularization [14 months]
Urgent non-target vessel revascularization [14 months]
Clinically indicated non-target vessel revascularization [14 months]
Transfusion rates both in patients with and/or without clinically detected over bleeding [14 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

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

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
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
If not on OAC,
Patient is on a DAPT regimen of aspirin and a P2Y12 inhibitor
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)
If on OAC
Patient is on the same type of OAC (e.g. Vitamin K antagonist or NOAC) for at least 7 days
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:

Treated with stents other than Ultimaster stent within 6 months prior to index procedure
Treated for in-stent restenosis or stent thrombosis at index PCI or within 6 months before
Treated with a bioresorbable scaffold at any time prior to index procedure
Cannot provide written informed consent
Under judicial protection, tutorship or curatorship
Unable to understand and follow study-related instructions or unable to comply with study protocol
Active bleeding requiring medical attention (BARC≥2) on randomization visit
Life expectancy less than one year
Known hypersensitivity or allergy for aspirin, clopidogrel, ticagrelor, prasugrel, cobalt chromium or sirolimus
Any planned and anticipated PCI
Participation in another trial
Pregnant or breast feeding women

Contacts and Locations

Locations

	Site	City	Country
1	Buenos Aires Research center	Buenos Aires	Argentina
2	Interventional Cardiology Sanatorio	Buenos Aires	Argentina
3	The Prince Charles Hospital	Chermside	Australia
4	St Vincents Hospital Melbourne	Melbourne	Australia
5	Research Center Perth	Perth	Australia
6	Research Center Sydney	Sydney	Australia
7	Wollongong Research Center	Wollongong	Australia
8	Research Center , 043-02	Wien	Austria
9	Research Center, 043-01	Wien	Austria
10	Research Centre Manama	Manama	Bahrain
11	Dhaka Research Center	Dhaka	Bangladesh
12	Research Center Aalst	Aalst	Belgium
13	Research Center Bonheiden	Bonheiden	Belgium
14	CHU st.Pierre	Bruxelles	Belgium
15	Research Centre Charleroi	Charleroi	Belgium
16	Research Center Hasselt	Hasselt	Belgium
17	Research Centre Liège	Liège	Belgium
18	MHAT Sveta Karidad Plovdiv	Plovdiv	Bulgaria
19	Sofia Resaerch Center, 359-02	Sofia	Bulgaria
20	Sofia Research Center, 359-01	Sofia	Bulgaria
21	Sofia Research Center, 359-03	Sofia	Bulgaria
22	Research Center Brno	Brno	Czechia
23	Research Center Phraha	Praha	Czechia
24	Research Center Roskilde	Roskilde	Denmark
25	Research Center Tallinn	Tallinn	Estonia
26	Research Center Annecy	Annecy	France
27	Hospital Prive Saint Martin	Caen	France
28	Research Centre Caen	Caen	France
29	Research Centre Créteil	Créteil	France
30	Research Center Dijon	Dijon	France
31	Hopital de la Timone	Marseille	France
32	Research Center Massy	Massy	France
33	Hospital de Mercy	Metz	France
34	Research Center Montauban	Montauban	France
35	Research Centre Montpellier	Montpellier	France
36	Research Center Nantes	Nantes	France
37	CHU Nimes	Nîmes	France
38	Research Center Paris, 033-05	Paris	France
39	Research Center Paris, 033-06	Paris	France
40	Research Centre Rouen	Rouen	France
41	Research Center Saint-Denis	Saint-Denis	France
42	Saarland University	Homburg	Germany
43	Cardiology Clinic	Landshut	Germany
44	Research Centre Budapest	Budapest	Hungary
45	Research Center Szeged	Szeged	Hungary
46	Research Center Chennai, 091-01	Chennai	India
47	Research Center Chennai, 091-05	Chennai	India
48	Research Center Coimbatore	Coimbatore	India
49	Research Center Surat	Sūrat	India
50	Research Center Haifa	Haifa	Israel
51	Research Center Jerusalem	Jerusalem	Israel
52	Rabin MC	Petah tikva	Israel
53	Research Center Safed	Safed	Israel
54	Ospedale Lorenzo Bonomo	Andria	Italy
55	Azienda Ospedaliera Brotzu	Cagliari	Italy
56	Second university of Naples Monaldi Hospital	Caserta	Italy
57	Research Center Catania	Catania	Italy
58	AOU Policlinico Gaetano Martino	Messina	Italy
59	Niguarda	Milan	Italy
60	Research Center Milan, 039-01	Milan	Italy
61	Research Center Milan, 039-04	Milan	Italy
62	Research Center Milan, 039-11	Milan	Italy
63	San Donato Hospital	Milan	Italy
64	Ospedale Sandro Pertini	Roma	Italy
65	Policlinico Casilino	Rome	Italy
66	Policlinico Umberto I	Rome	Italy
67	Research Center Rozzano	Rozzano	Italy
68	Clinic Cardiology	Treviglio	Italy
69	Research Center Vimercate	Vimercate	Italy
70	Kokura Memorial Hospital	Fukuoka	Japan
71	Research Center Gifu	Gifu	Japan
72	Ichinomiya Municipal Hospital	Ichinomiya	Japan
73	St.Marianna University School of Medicine	Kawasaki	Japan
74	Aichi Medical University Hospital	Nagakute	Japan
75	Japan Red Cross Nagoya Daiichi Hospital (1st)	Nagoya	Japan
76	Japan Red Cross Nagoya Daini Hospital (2nd)	Nagoya	Japan
77	Nagoya University Hospital	Nagoya	Japan
78	Osaka police Hospital	Osaka	Japan
79	St.Luke's International Hospital	Tokyo	Japan
80	Research Center Toyoake	Toyoake	Japan
81	Research Center Seoul	Seoul	Korea, Republic of
82	Research Center Den Bosch	's Hertogenbosch	Netherlands
83	Research Centre Arnhem	Arnhem	Netherlands
84	Research Center Breda	Breda	Netherlands
85	Research Centre Dordrecht	Dordrecht	Netherlands
86	Research Centre Eindhoven	Eindhoven	Netherlands
87	Research Center Emmen	Emmen	Netherlands
88	Research Centre Enschede	Enschede	Netherlands
89	Antonius ziekenhuis	Nieuwegein	Netherlands
90	Research Center Rotterdam	Rotterdam	Netherlands
91	Research Centre Terneuzen	Terneuzen	Netherlands
92	Haga Hospital	The Hague	Netherlands
93	Research Center Skopje	Skopje	North Macedonia
94	University Hospital Krakow	Krakow	Poland
95	Research Center Krakow	Kraków	Poland
96	Miedziowe Centrum Zdrowia SA	Lubin	Poland
97	Research Center Poznan	Poznań	Poland
98	Research Centre Wroclaw	Wrocław	Poland
99	Research Center Jeddah	Jeddah	Saudi Arabia
100	Research Center Riyadh	Riyadh	Saudi Arabia
101	Researcg Center Belgrade, 381-02	Belgrade	Serbia
102	Research Center of Serbia, 381-01	Belgrade	Serbia
103	Research Center Sremska Kamenica	Sremska Kamenica	Serbia
104	Singapore Research Center	Singapore	Singapore
105	Tan Tock Seng Hospital	Singapore	Singapore
106	Ljubljana Research Center	Ljubljana	Slovenia
107	Research Center Alicante	Alicante	Spain
108	Research Center Barcelona, 034-07	Barcelona	Spain
109	Research Center Barcelona, 034-09	Barcelona	Spain
110	Universitario Virgen de la Arrixaca	El Palmar	Spain
111	Research Center Huelva	Huelva	Spain
112	Hospital Universitario Puerta de hierro	Madrid	Spain
113	Research Center Madrid, 034-06	Madrid	Spain
114	Research Center Madrid, 034-10	Madrid	Spain
115	Hospital Universitario Valdecilla	Santander	Spain
116	Research Center Vigo	Vigo	Spain
117	Research Center Gavle	Gävle	Sweden
118	Research Center Orebro	Örebro	Sweden
119	Lindenhofspital	Bern	Switzerland
120	Research Centre Bern	Bern	Switzerland
121	Research Centre Fribourg	Fribourg	Switzerland
122	University Hospital Geneva	Geneva	Switzerland
123	Research Centre Liestal	Liestal	Switzerland
124	Research Centre Lugano	Lugano	Switzerland
125	Research Centre Zürich	Zürich	Switzerland
126	Research Center Blackburn	Blackburn	United Kingdom
127	Research Center Bournemouth	Bournemouth	United Kingdom
128	Research Centre Brighton	Brighton	United Kingdom
129	Bristol Heart Institute	Bristol	United Kingdom
130	Altnagelvin Hospital	Derry	United Kingdom
131	St George's Hospital	London	United Kingdom
132	Manchester Research Center	Manchester	United Kingdom
133	Research Center Newcastle	Newcastle Upon Tyne	United Kingdom
134	Research Center Stevenage	Stevenage	United Kingdom
135	Research Centre Stoke-on-Trent	Stoke-on-Trent	United Kingdom
136	Research Centre Wolverhampton	Wolverhampton	United Kingdom
137	Research Centre Worcester	Worcester	United Kingdom
138	Vietnam National Heart Institute	Hanoi	Vietnam

Sponsors and Collaborators

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

Investigators

Principal Investigator: M. Valgimigli, Prof., Cardiocentro Ticino Foundation, Lugano, Switzerland
Principal Investigator: P. Smits, Dr., Maasstad Ziekenhuis Rotterdam, The Netherlands
Study Director: E. Spitzer, Dr., ECRI bv