Clinical Trials Register

Summary
EudraCT Number:	2013-005571-40
Sponsor's Protocol Code Number:	9207
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2014-11-11
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2013-005571-40

A.3

Full title of the trial

Randomized Evaluation of short-term DUal anti platelet therapy in patients with acute coronary syndrome treated with the COMBO dual-therapy stEnt

Valutazione randomizzata della doppia terapia antiaggregante a breve termine in pazienti affetti da sindrome coronarica acuta sottoposti a impianto di stent COMBO doppia terapia

A.3.1

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

Randomized Evaluation of short-term DUal anti platelet therapy in patients with acute coronary syndrome treated with the COMBO dual-therapy stEnt

Valutazione randomizzata della doppia terapia antiaggregante a breve termine in pazienti affetti da sindrome coronarica acuta sottoposti a impianto di stent COMBO doppia terapia

A.3.2

Name or abbreviated title of the trial where available

REDUCE

A.4.1

Sponsor's protocol code number

9207

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	Diagram B.V.
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	OrbusNeich
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Diagram B.V.
B.5.2	Functional name of contact point	Reduce Study Information, J. Klijn
B.5.3	Address:
B.5.3.1	Street Address	Van Nahuysplein 6
B.5.3.2	Town/ city	Zwolle
B.5.3.3	Post code	8011NB
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	00310384242999
B.5.5	Fax number	00310384242990
B.5.6	E-mail	reduce.study@diagram-zwolle.nl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	Aspirin
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	Aspirin
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.3.11 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	Comparator
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	Clopidrogel
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	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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	Comparator
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	Prasugrel
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	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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: 4
D.1.2 and D.1.3	IMP Role	Comparator
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	Ticagrelor
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	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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

Acute coronary syndrome

Sindrome coronarica acuta

E.1.1.1

Medical condition in easily understood language

Occlusion/obstruction blood vessel of the heart

Occlusione/Ostruzione delle coronarie

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	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10064348
E.1.2	Term	Non STEMI
E.1.2	System Organ Class	100000004849

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10064346
E.1.2	Term	STEMI
E.1.2	System Organ Class	100000004849

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10002385
E.1.2	Term	Angina pectoris unstable
E.1.2	System Organ Class	100000004849

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate safety of 3-months versus standard 12-months of DAPT

valutare la sicurezza della terapia aggregante (DAPT) doppia a 3 mesi verso la DAPT a 12 mesi

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. The patient must be ≥18 years of age
2. The patient has been diagnosed with STEMI, NSTEMI or UA
3. The Patient is willing to comply with specified follow-up evaluations
4. The Patient has been informed of the nature of the study, agrees to its provisions and has been provided written informed consent, approved by the appropriate Medical Ethics Committee (MEC), Institutional Review Board (IRB), or Human Research Ethics Committee (HREC)
5. Successful COMBO stent implantation (TIMI 3 flow with residual stenosis < 20% based visual estimation), with no clinical adverse event during hospitalization (Death, stent thrombosis (ST), stroke, target vessel revascularisation (TVR), bleeding (BARC II, III, V))

1.Il paziente deve aver compiuto i 18 anni di età
2.Il paziente deve essere stato colpito da STEMI, NSTEMI o angina instabile
3.Il paziente deve essere disposto ad essere sottoposto a visite di controllo specifiche
4.Il paziente deve essere stato informato circa la natura dello studio, accettarne le condizioni e aver ricevuto una copia scritta del consenso informato, approvato dal comitato etico o comitato istituzionale di revisione (IRB) competenti, oppure da un comitato etico per la sperimentazione sull'uomo (HREC)
5.Introduzione riuscita di uno stent COMBO (flusso TIMI 3 con stenosi residua < 20% stimata visivamente), senza alcun evento avverso durante la degenza in ospedale (morte, ST, ictus, TVR o emorragia (BARC II, III, V))

E.4

Principal exclusion criteria

1. Patients presenting with cardiogenic shock
2. Patients with recent major bleeding complications or contraindication to DAPT, such as:
a) Hypersensitivity to Aspirin, Clopidogrel, Prasugrel or Ticagrelor
b) Need for oral anticoagulation
c) History of bleeding diathesis or known coagulopathy (including heparin-induced thrombocytopenia) or refusal of blood transfusions
d) History of intracerebral mass, aneurysm, arteriovenous malformation, or hemorrhagic stroke
e) Stroke or transient ischemic attack within the past 6 months or any permanent residual neurologic defect
f) Gastrointestinal or genitourinary bleeding within the last 2 months or major surgery within 6 weeks
g) Recent history or known current platelet count <100 000 cells/mm3 or hemoglobin <10 g/dL
h) An elective surgical procedure is planned that would necessitate interruption of thienopyridines during the first 12 months post enrollment
3. Planned need for concomitant cardiac surgery (e.g., valve surgery or resection of aortic or left ventricular aneurysm etc.)
4. Planned intervention of another lesion (target vessel or non-target vessel) after index hospital discharge
5. Any revascularization performed within index hospitalization with other stents than COMBO
6. Potential for non-compliance towards the requirements in the trial protocol (especially the medical treatment) or follow-up visits
7. Patients requiring permanent DAPT due to comorbidities
8. Patient has received any organ transplant or is on a waiting list for any organ transplant
9. Life expectancy of less than 2 years
10. Pregnancy or intention to become pregnant during the course of the trial
11. Any significant medical or mental condition, which in the Investigator’s opinion may interfere with the patient’s optimal participation in the study
12. Currently participating in another investigational drug or device study
13. Patients who have been treated with another DES within 9 months prior to the index procedure

1. Pazienti affetti da shock cardiogeno
2. Pazienti con una storia recente di emorragie gravi o controindicazioni alla DAPT, quali:
a) intolleranza ad Aspirina, Clopidogrel, Prasugrel o Ticagrelor
b) necessità di assumere una terapia anticoagulante per via orale
c) storia di diatesi emorragiche o coagulopatie note (incluse le trombocitopenie indotte da eparina) o pazienti che rifiutino trasfusioni
d) storia di masse intracraniche, aneurismi, malformazioni artero-venose o ictus emorragici
e) ictus o attacchi ischemici transitori negli ultimi 6 mesi, o qualsiasi altro deficit neurologico residuo e permanente
f) emorragie gastrointestinali o genitourinarie negli ultimi 2 mesi o interventi chirurgici importanti nelle ultime 6 settimane
g) storia recente (<3 mesi precedenti alla randomizzazione) o condizione attuale di conta piastrinica <100.000 cell/mm3 o emoglobina <10 g/dl
h) qualora sia stato programmato un intervento chirurgico di elezione che renderebbe necessaria l'interruzione delle tienopiridine nei 12 mesi successivi all'inclusione
3. Necessità programmata di un intervento cardiochirurgico (p. es. intervento sulle valvole, resezione di un aneurisma aortico o ventricolare sinistro, ecc.)
4. Intervento programmato su una lesione di altro tipo (vaso target o non target) successivo alla dimissione
5. Ogni rivascolarizzazione effettuata durante l'ospedalizzazione indice con stent non COMBO
6. Possibilità che le condizioni previste dal protocollo non vengano rispettate (in particolar modo per quanto riguarda il trattamento medico) o che le visite di controllo non vengano effettuate
7. Pazienti che hanno bisogno di una DAPT ininterrotta a causa di altre condizioni cliniche contemporanee
8. Pazienti che sono stati sottoposti ad un trapianto d'organo o che sono in lista d'attesa per un trapianto
9. Aspettativa di vita inferiore a 2 anni
10. Gravidanza o intenzione di avviare una gravidanza nel corso dello studio
11. Qualsiasi condizione medica o mentale degna di nota, che a giudizio dell'investigatore possa essere d'ostacolo ad una partecipazione ottimale allo studio da parte del paziente
12. Partecipazione contemporanea ad un altro studio clinico che abbia come oggetto un farmaco o un dispositivo
13. Pazienti trattati con DES nei 9 mesi precedenti alla procedura indice

E.5 End points

E.5.1

Primary end point(s)

Composite of all cause mortality, myocardial infarction (MI), stent thrombosis (ST), stroke, bleeding (BARC II, III, V) at 12 months

Endpoint primario è un composito di morte per tutte le cause, infarto miocardico (IM), trombosi dello stent (ST), ictus, rivascolarizzazione del vaso target (TVR) o emorragia (BARC II, III, V) a 12 mesi.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months

12 mesi

E.5.2

Secondary end point(s)

- Bleeding (BARC II, III, V) at 12 months
- All cause mortality, MI, ST, stroke, bleeding (BARC II, III, V) at 24 months
- All cause mortality, MI, ST, stroke at 12 and 24 months
- Cardiac Mortality at 12 and 24 months
- Any MI at 12 and 24 months
- ST at 12 and 24 months
- Repeat revascularization at 12 and 24 months
- Time to event analysis primary endpoint

-Emorragie (BARC II, III, V) a 12 mesi
-Morte per tutte le cause, IM, ST, ictus, TVR, emorragia (BARC II, III, V) a 12 e 24 mesi
-Morte per tutte le cause, IM, ST, ictus e TVR a 12 e 24 mesi
-Morte per tutte le cause a 12 e 24 mesi
-Morte cardiaca a 12 e 24 mesi
-Tutti i casi di IM a 12 e 24 mesi
-ST a 12 e 24 mesi
-Rivascolarizzazione ripetuta a 12 e 24 mesi
-Tempo all'evento, definito dall'insorgere di uno dei seguenti eventi: morte per tutte le cause, IM, ST, ictus, TVR o emorragia (BARC II, III, V) entro 12 e 24 mesi
-Analisi di landmark prestabilita dell'endpoint primario (senza TVR) da 3 a 12 mesi

E.5.2.1

Timepoint(s) of evaluation of this end point

- time to event primary endpoint
- 12 months
- 24 months

-tempo all'evento dell'endpoint primario
-12 mesi
-24 mesi

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

E.6.4

Safety

Yes

E.6.5

Efficacy

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

La durata della somministrazione dei farmaci è più lunga

Duration of administration of drugs is longer

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

Belgium

Germany

Hong Kong

Hungary

Indonesia

Italy

Malaysia

Netherlands

Poland

Singapore

Thailand

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

The last visit of the last patient

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:

750

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

750

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

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

250

F.4.2

For a multinational trial

F.4.2.1

In the EEA

750

F.4.2.2

In the whole clinical trial

1500

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

Nessuno

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

2015-02-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-02-13

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

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Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
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