Clinical Trials Register

Summary
EudraCT Number:	2017-001834-25
Sponsor's Protocol Code Number:	MasterDapt_Sweden
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2017-11-01
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Sweden - MPA

A.2

EudraCT number

2017-001834-25

A.3

Full title of the trial

MAnagement of high bleeding risk patients post bioresorbable polymer coated STEnt implantation with an abbReviated versus prolonged DAPT regimen (MASTER-DAPT)

Hantering av patienter med hög blödningsrisk, efter implantation av stent med biologiskt resorberbar polymer, med antingen en förkortad eller en förlängd DAPT-behandling (MASTER-DAPT)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

To compare two medication therapies to prevent thrombus (blood cloth) formation following the successful treatment of a coronary heart disease with expansion of coronary stent (metallic tube) covered with medication (Drug Eluting Stent-DES): a shortened versus a prolonged dual antiplatelet therapy (DAPT, drugs that inhibit bloodplatelets, blood cells involved in the thrombus formation process).

Hantering av patienter med hög blödningsrisk, efter implantation av stent (tubformat stålnät) innehållande biologiskt nedbrytbar polymer, med antingen en förkortad eller en förlängd dubbel blodförtunnande behandling (MASTER - DAPT)

A.3.2

Name or abbreviated title of the trial where available

MASTER-DAPT

A.4.1

Sponsor's protocol code number

MasterDapt_Sweden

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ECRI-9
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Terumo Europe NV
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ECRI-9
B.5.2	Functional name of contact point	Managing Director
B.5.3	Address:
B.5.3.1	Street Address	Westblaak 98
B.5.3.2	Town/ city	Rotterdam
B.5.3.3	Post code	3012 KM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	0031102062828
B.5.5	Fax number	0031102062844
B.5.6	E-mail	info@ecri-trials.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Trombyl 75 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Trombyl
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ACETYLSALICYLIC ACID
D.3.9.1	CAS number	50-78-2
D.3.9.2	Current sponsor code	ACETYLSALICYLIC ACID
D.3.9.3	Other descriptive name	ACETYLSALICYLIC ACID
D.3.9.4	EV Substance Code	SUB12730MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	75
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Brilique 90 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca AB
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Brilique
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ticagrelor
D.3.9.1	CAS number	274693-27-5
D.3.9.2	Current sponsor code	Ticagrelor
D.3.9.3	Other descriptive name	TICAGRELOR
D.3.9.4	EV Substance Code	SUB30898
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2x90
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Plavix 75 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Plavix
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Clopidogrel
D.3.9.1	CAS number	113665-84-2
D.3.9.2	Current sponsor code	Clopidogrel
D.3.9.3	Other descriptive name	CLOPIDOGREL
D.3.9.4	EV Substance Code	SUB13395MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	75
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

High bleeding risk population represents a significant proportion of coronary artery disease (CAD) patients undergoing coronary stent implantation. Decisions regarding the duration of dual antiplatelet therapy (DAPT) after stent implantation are difficult, especially after implantation of newer generation drug eluting stents (DES) due to conflicting results from recent trials. High bleeding risk patients either male or female eligible for percutaneous coronary intervention will be included.

E.1.1.1

Medical condition in easily understood language

Patients with different levels of chest pain, due to poor blood flow to the heart, and an increased risk for bleeding. A stent is placed to reopen the artery followed by treatment with medicines.

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10007541
E.1.2	Term	Cardiac disorders
E.1.2	System Organ Class	10007541 - Cardiac disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The objective is to compare, within current guidelines and instructions for use, an abbreviated versus a prolonged DAPT duration after bioresorbable polymer coated Ultimaster sirolimus-eluting stent implantation in patients presenting High Bleeding Risk features.

Studiens syfte är att jämföra, inom nuvarande guidelines och användarinstruktioner, en förkortad mot en förlängd DAPT-behandling efter implantation av Ultimaster stent överdragen med bioresorberbar polymer i patienter med hög risk för blödning.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal 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 High Bleeding Risk (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.
Inclusion criteria at one-month randomization visit
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,
a.Patient is on a DAPT regimen of aspirin and a P2Y12 inhibitor
b.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
a.Patient is on the same type of OAC (e.g. Vitamin K antagonist or NOAC) for at least 7 days
b.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 inclusion.
•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

E.4

Principal exclusion criteria

Patients are not eligible if any of the following applies
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

E.5 End points

E.5.1

Primary end point(s)

This study has 3 primary endpoints:
1)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
2)Major adverse cardiac and cerebral events (MACCE) defined as a composite of all-cause death, myocardial infarction and stroke
3)Major or clinically relevant non-major bleeding (MCB) defined as a composite of type 2, 3 and 5 BARC bleeding events
The main analyses evaluate the occurrence of the primary endpoints between randomization and 11 months thereafter. In secondary analyses, the occurrence of primary endpoints between randomization and 15 months after index PCI is evaluated.

E.5.1.1

Timepoint(s) of evaluation of this end point

11 and 15 months after randomization

E.5.2

Secondary end point(s)

The secondary endpoints of the study are the following:
1)The individual components of each primary endpoint
2)The composite of cardiovascular death, MI, and stroke
3)The composite of cardiovascular death, MI, and urgent revascularization
4)The composite of cardiovascular death, MI, and any unplanned revascularization
5)Death from cardiovascular causes
6)The composite of definite or probable stent thrombosis
7)Myocardial infarction
8)Any target lesion revascularisation
9)Urgent target lesion revascularization
10)Any target vessel revascularization
11)Urgent target vessel revascularization
12)Any non-target vessel revascularization
13)Any urgent non-target vessel revascularization
14)Bleeding events according to the BARC, TIMI and GUSTO classification
15)Transfusion rates both in patients with and/or without clinically detected over bleeding

E.5.2.1

Timepoint(s) of evaluation of this end point

11 and 15 months after randomization

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Long term Dual Antiplatelet Therapy

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Austria

Bahrain

Belgium

Czech Republic

Estonia

France

Germany

Hungary

India

Italy

Korea, Republic of

Macedonia, the former Yugoslav Republic of

Netherlands

Poland

Saudi Arabia

Serbia

Spain

Sweden

Switzerland

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

430

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

3870

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2017-11-01.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

150

F.4.2

For a multinational trial

F.4.2.1

In the EEA

2800

F.4.2.2

In the whole clinical trial

4300

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-01-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-05-03

P. End of Trial
P.	End of Trial Status	Ongoing

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