Clinical Trials Register

Summary
EudraCT Number:	2009-015712-17
Sponsor's Protocol Code Number:	G080186
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-03-10
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

Czechia - SUKL

A.2

EudraCT number

2009-015712-17

A.3

Full title of the trial

A prospective, multi-center, randomized, double-blind trial to assess the
effectiveness and safety of 12 versus 30 months of dual antiplatelet therapy
(DAPT) in subjects undergoing percutaneous coronary intervention (PCI) with
either drug-eluting stent (DES) or bare metal stent (BMS) placement for the
treatment of coronary artery lesions.

A.3.1

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

The DAPT Study is a double blind randomized controlled trial intended to determine the appropriate duration for dual antiplatelet therapy (the combination of aspirin and a second anti-clotting medication) as well as the safety and effectiveness of dual antiplatelet therapy to protect patients from stent thrombosis and major adverse cardiovascular and cerebrovascular events (MACCE) following the implantation of drug-eluting coronary stents.

A.3.2

Name or abbreviated title of the trial where available

DAPT Study

A.4.1

Sponsor's protocol code number

G080186

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00977938

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	HCRI
B.1.3.4	Country	United States
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Plavix
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Pharma Bristol-Myers Squibb SNC
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	Pharmaceutical form	Film-coated 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.3.9.3	Other descriptive name	Clopidogrel bisulfate
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	Efient
D.2.1.1.2	Name of the Marketing Authorisation holder	Eli Lilly
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	Pharmaceutical form	Film-coated 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	Prasugrel
D.3.9.1	CAS number	389574-19-0
D.3.9.2	Current sponsor code	LY640315 Hydrochloride salt
D.3.9.3	Other descriptive name	LY640315
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	5
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	Efient
D.2.1.1.2	Name of the Marketing Authorisation holder	Eli Lilly
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	Pharmaceutical form	Film-coated 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	Prasugrel
D.3.9.1	CAS number	389574-19-0
D.3.9.2	Current sponsor code	LY640315 Hydrochloride salt
D.3.9.3	Other descriptive name	LY640315
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	10
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 3
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Dual antiplatelet therapy (DAPT) in subjects undergoing percutaneous coronary intervention (PCI) with either drug eluting stent (DES) or bara metal stent (BMS) placement for the treatment of coronary artery lesions.

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	13.1
E.1.2	Level	LLT
E.1.2	Classification code	10055218
E.1.2	Term	Ischemic heart disease
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 objectives of this study are to evaluate the composite of all death, myocardial infarction (MI) and stroke (MACCE) and the survival free from ARC definite or probable stent thrombosis (ST) in subjects treated with drug eluting stents (DES) and extended dual antiplatelet therapy. All of the primary analyses will be performed on the primary analysis population (randomized DES subjects followed through 33
months post-procedure, including the 3 month rebound observational period).

E.2.2

Secondary objectives of the trial

The main secondary study hypotheses are:

DAPT subjects treated with drug-eluting stents who are free from myocardial
infarction, repeat coronary revascularization, stroke, stent thrombosis, or
bleeding in the first 12 months after stenting and DAPT, will have a rate of
death, myocardial infarction or stroke that is non-inferior compared with the rate
of propensity score matched subjects treated with bare-metal stents over the 12-
33 month post-stenting period.

DAPT subjects treated with drug-eluting stents who are free from myocardial
infarction, repeat coronary revascularization, stroke, stent thrombosis, or
bleeding in the first 12 months after stenting and DAPT, will have a rate of ARC
definite/probable stent thrombosis (ST) that is non-inferior compared with the
rate of propensity score matched subjects treated with bare-metal stents over the
12-33 month post-stenting period.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Enrollment inclusion criteria:
Subject must meet all of the following criteria to be eligible for treatment in the study:
1. Subject is > 18 years of age.
2. Subjects undergoing percutaneous intervention with stent deployment (or has w/in 3 calendar days).
3. Subjects without known contraindication to dual antiplatelet therapy for at least
30 months after enrollment and stent implantation.
4. The subject has consented to participate and has authorized the collection and
release of his medical information by signing the “Patient Informed Consent Form”. The informed consent will be valid for the duration of the trial or until the subject withdraws.

Randomisation inclusion criteria:
Subject is “12 Month Clear”, defined as subjects who are treated with 12 months of DAPT post index procedure and who are event free (from all death, myocardial infarction, stroke, repeat coronary revascularization, stent thrombosis, and major bleeding – “severe” or “moderate” by GUSTO classification) during that time. During the open label portion of this study (time 0-12m post-index procedure), a subject is considered compliant with the thienopyridine therapy for the purposes of eligibility if they take between 80% and 120% of the prescribed drug in the 0-6 month and 6-12 month periods without an interruption of therapy longer than 14 days

E.4

Principal exclusion criteria

Enrollment exclusion criteria:
1. Index procedure stent placement with stent diameter <2.25 mm or >4.0 mm.
2. Pregnant women.
3. Planned surgery necessitating discontinuation of antiplatelet therapy (>14 days) within the 30 months following enrollment.
4. Current medical condition with a life expectancy of less than 3 years.
5. Concurrent enrollment in another device or drug study where the primary endpoint has not yet been reached or the device/drug might affect major endpoint outcomes in either open label or randomized phases of the DAPT study. The subject may only be enrolled in the DAPT Study once.
6. Subjects on long-term warfarin (or similar anticoagulant) therapy who are anticipated to still be on warfarin at the time of randomization.
7. Subjects with hypersensitivity or allergies to one of the drugs or components
indicated in the Instructions for Use for the device implanted.
8. Subjects unable to give informed consent.
9. Subject treated with both DES and BMS during the index procedure.

Randomisation exclusion criteria:
1. Pregnant women.
2. Subject switched thienopyridine type or dose within 6 months prior to randomization.
NOTE: thienopyridine switching during the open label portion of this study is
discouraged.
3. Percutaneous coronary intervention or cardiac surgery between 6 weeks post
index procedure and randomization.
4. Planned surgery necessitating discontinuation of antiplatelet therapy (>14 days) within the 21 months following randomization.
5. Current medical condition with a life expectancy of less than 3 years.
6. Subjects on warfarin or similar anticoagulant therapy.

E.5 End points

E.5.1

Primary end point(s)

Co-Primary Endpoints:

Incidence of composite of all death, myocardial infarction (MI) and stroke
(defined as MACCE) 12-33 months post-stent.
Incidence of ARC definite or probable stent thrombosis (ST) 12-33 months poststent.

Primary Safety Endpoint:

Major bleeding (GUSTO classification, severe and moderate bleeding combined)
12-33 months post-stent

E.5.1.1

Timepoint(s) of evaluation of this end point

Through-out treatment period

E.5.2

Secondary end point(s)

" DAPT subjects treated with drug-eluting stents will have a rate of death, myocardial infarction
or stroke that is non-inferior compared with the rate of propensity score matched subjects
treated with bare-metal stents over the 0-33 month post-stenting period.
 DAPT subjects treated with drug-eluting stents will have a rate of ARC definite/probable stent
thrombosis (ST) that is non-inferior compared with the rate of propensity score matched
subjects treated with bare-metal stents over the 0-33 month post-stenting period."

E.5.2.1

Timepoint(s) of evaluation of this end point

Through-out treatment period

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

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

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

Yes

E.8.1.7.1

Other trial design description

The first 12 months are open, then it is a double blind

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

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

Czech Republic

France

Germany

Hungary

Poland

Romania

United Kingdom

United States

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

Last visit of last subject

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.2.1	Number of subjects for this age range:	20645
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
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 2010-03-10.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	415
F.4.2	For a multinational trial
F.4.2.1	In the EEA	3672
F.4.2.2	In the whole clinical trial	20645

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

2010-05-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-05-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-05-08

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