Clinical Trials Register

Summary
EudraCT Number:	2021-005499-20
Sponsor's Protocol Code Number:	RM21
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2022-05-18
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

Netherlands - Competent Authority

A.2

EudraCT number

2021-005499-20

A.3

Full title of the trial

COMPARE STEMI ONE- Comparison Of reduced DAPT followed by P2Y12 inhibitor Monotherapy with Prasugrel vs stAndard Regimen in STEMI patients treated with OCT-guided vs aNgio-guided completE revascularization.

Compare Stemi One: Vergelijking van een verkorte DAPT gevolgd door een enkelvoudige behandeling met de P2Y12 remmer Prasugrel met een standaard regiem in STEMI patiënten behandeld met OCT gestuurde volledige revascularisatie ten opzichte van Angio gestuurde volledige revascularisatie

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

Compare Stemi One

A.4.1

Sponsor's protocol code number

RM21

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	Research Maatschap Cardiologen Rotterdam Zuid
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	Abbott Vascular International BVBA
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	Research Maatschap Cardiologen Rotterdam Zuid
B.5.2	Functional name of contact point	Ria van Vliet, project manager
B.5.3	Address:
B.5.3.1	Street Address	Maasstadweg 21
B.5.3.2	Town/ city	Rotterdam
B.5.3.3	Post code	3079 DZ
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	31644162844
B.5.5	Fax number	31102913065
B.5.6	E-mail	vlietM@maasstadziekenhuis.nl

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.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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: 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.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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

ST elevated myocard infarction followed by PCI

ST elevatie myocardial infarction gevolgd door PCI

E.1.1.1

Medical condition in easily understood language

Acute heart infarct followed by dotterprocedure

Acuut hart infarct gevolgd door een dotterprocedure

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

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 primary objective of this study is to prove noninferiority regarding safety and effectiveness of 30-45 day of DAPT followed by Prasugrel-monotherapy versus standard 12 months of DAPT in patients admitted for STEMI treated by primary PCI.

The ancillary objective of the study is to prove that OCT-guided revascularization completion by staged PCI is superior to an angio-guided approach in patients with multivessel disease who have received guideline-based treatment of the culprit lesion.

Het primaire doel van deze studie is om non-inferioriteit met betrekking tot veiligheid en effectiviteit van 30-45 dagen DAPT te bewijzen, gevolgd door Prasugrel-monotherapie versus standaard 12 maanden DAPT bij patiënten die zijn opgenomen voor STEMI behandeld met primaire PCI.

Het nevendoel van de studie is om te bewijzen dat OCT-geleide complete revascularisatie in staged PCI superieur is aan een angiogeleide benadering bij patiënten met meervatslijden die een op richtlijnen gebaseerde behandeling van de doelvat laesie hebben gekregen.

E.2.2

Secondary objectives of the trial

not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion Criteria at index procedure
All STEMI patients who are planned to be treated with PCI:

ST segment elevation myocardial infarction:
Chest discomfort suggestive of cardiac ischemia ≥20 min at rest with 1 of the following ECG features:
• ST segment elevation ≥2 contiguous ECG leads
• new or presumably new left bundle branch block

Inclusion Criteria at 30-45 days
• All patients who have provided informed consent
• Compliance to DAPT with no regimen modifications (Non-adherence Academic Research Consortium 0)
• No occurrence of significant event (such as MI, unplanned revascularisation, stent thrombosis, stroke, major vascular complication/bleeding BARC Types 3 or greater).
• Successful revascularization: - Successful delivery and deployment of the Study device(s), with final residual stenosis of <30% (visually) for all target lesions.
• Complete revascularization performed when more than 1 significant lesion during staged procedure(s) occurring within 15 days from the index procedure. Physiologic assessment highly recommended for lesions with stenosis between 50% and 90%.

IInclusie criteria bij de index procedure
Alle STEMI-patiënten die gepland zijn om te worden behandeld met PCI

ST segment elevatie myocardinfarct:
Pijn op de borst dat wijst op cardiale ischemie ≥20 minuten in rust met 1 van de volgende ECG-kenmerken:
• ST-segment elevatie in ≥2 aaneengesloten ECG-afleidingen
• nieuw of vermoedelijk nieuw linkerbundeltakblok

Inclusie Criteria bij 30-45 dagen
• Alle patiënten, die informed consent hebben gegeven
• Naleving van DAPT zonder regimewijzigingen (Non-adherence Academic Research Consortium 0)
• Geen significante gebeurtenis (zoals MI, ongeplande revascularisatie, stenttrombose, beroerte, ernstige vasculaire complicatie/bloeding BARC Types 3 of hoger).
• Succesvolle revascularisatie: - Succesvolle ontplooiing en plaatsing van de studie stent, met uiteindelijke resterende stenose van <30% (visueel) voor alle doellaesies.
• Volledige revascularisatie wanneer meer dan 1 significante laesie aanwezig, tijdens de gefaseerde procedure (s) uitgevoerd binnen 15 dagen na de indexprocedure. Fysiologische beoordeling sterk aanbevolen voor laesies met stenose tussen 50% en 90%.

E.4

Principal exclusion criteria

Patients on oral anticoagulation
- Contraindication to P2Y12 inhibitors and/or to Cardioaspirin or to any of the excipients (hypersensitivity, history of any stroke or transient ischemic attack within the last 12 months, active bleeding or haemorrhagic diathesis, fibrin-specific fibrinolytic therapy less than 24 h before randomization, severe hepatic dysfunction (Child-Pugh C), history of asthma induced by the administration of salicylates or substances with a similar action, notably non-steroidal anti-inflammatory medicines, history of gastrointestinal perforation or acute gastrointestinal ulcers, severe cardiac failure (NYHA grade III or IV), combination with methotrexate at doses of 15 mg/week or more).
- Patients who have received P2Y12 inhibitors other than Prasugrel in the ambulance (Ticagrelor or Clopidogrel loading dose) or are already on P2Y12 inhibitors, may be enrolled in the protocol, provided that the Prasugrel loading dose is administered at admission, according to current guidelines recommendations (see section 5.2.2).
- Concomitant oral or i.v. therapy with strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, grapefruit juice >1L/day), CYP3A substrates with narrow therapeutic indices (e.g., cyclosporine, quinidine), or strong CYP3A inducers (e.g., rifampin)
- rifampicin, phenytoin, carbamazepine, dexamethason, phenobarbital
- Platelet count <100.000/μL at the time of screening
- Anemia (hemoglobin <10 g/dL) at the time of screening
- Comorbidities associated with life expectancy <1 year
- Pregnancy, giving birth within the last 90 days, or lactation (see appendix III for women of childbearing potential)
- PCI indication for stent thrombosis or previous history of definite stent thrombosis
- Non-deferrable major surgery on DAPT after PCI
- Cardiogenic shock
- Out of hospital cardiac arrest (OHCA) unless survivors of ventricular arrythmia with prompt return of spontaneous circulation (ROSC)
- Patients with severe renal impairment: creatinine clearance ≤30 ml/min/1.73 m2 (as calculated by MDRD formula for estimated GFR).
- Patients participating in another interventional (device of drug trial) within the previous 12 months or patients to whom an investigational drug was administered in the 30 days prior to screening, or 5 half-lives of the study drug, whichever is longer.
- No informed consent

• Patiënten op orale antistolling
• Contra-indicatie voor P2Y12-remmers en/of Asperin (overgevoeligheid, voorgeschiedenis van een beroerte of voorbijgaande ischemische aanval in de afgelopen 12 maanden, actieve bloedingen, fibrinespecifieke fibrinolytische therapie minder dan 24 uur vóór randomisatie, chronische nierinsufficiëntie die dialyse vereist, matige of ernstige leverdisfunctie)
• Gelijktijdige orale of i.v. therapie met sterke CYP3A-remmers (bijv. ketoconazol, itraconazol, voriconazol, telithromycine, claritromycine, nefazodon, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, grapefruitsap >1L/dag), CYP3A-substraten met smalle therapeutische indices (bijv. ciclosporine, kinidine) of sterke CYP3A-inductoren (bijv. rifampicine)
• rifampicine, fenytoïne, carbamazepine, dexamethason, fenobarbital
• Aantal bloedplaatjes <100.000/μL op het moment van screening
• Bloedarmoede (hemoglobine <10 g / dL) op het moment van screening
• Co-morbiditeiten geassocieerd met levensverwachting <1 jaar
• Zwangerschap, bevallen in de laatste 90 dagen, of borstvoeding
• PCI-indicatie voor stenttrombose of voorgeschiedenis van definitieve stenttrombose
• Niet-uitstelbare grote operatie onder DAPT medicatie na PCI
• Cardiogene shock
• Hartstilstand buiten het ziekenhuis (OHCA), tenzij overlevenden van Ventriculaire Aritmie met prompte terugkomst van spontane circulatie.
* Patiënten met ernstige nierinsufficiëntie: creatinineklaring ≤30 ml/min/1,73 m2 (zoals berekend met MDRD-formule voor geschatte GFR).
* Patiënten die in de voorgaande 12 maanden deelnamen aan een ander interventioneel (hulpmiddel of geneesmiddelenonderzoek) of patiënten aan wie een onderzoeksgeneesmiddel werd toegediend in de 30 dagen voorafgaand aan de screening, of 5 halfwaardetijden van het onderzoeksgeneesmiddel, afhankelijk van wat langer is
• Geen geïnformeerde toestemming

E.5 End points

E.5.1

Primary end point(s)

The first primary objective of this Open-label, Randomized, Controlled Clinical Trial is to demonstrate the non inferority of a Prasugrel-based short DAPT (30-45 days) followed by 11-month Prasugrel monotherapy versus standard DAPT regimen by assessing:
- Incidence of Net Adverse Clinical Events (NACE) at 11 months post DAPT randomization as composite of death, MI, stroke or BARC bleeding 3 or 5

The co-primary objective is to demonstrate in patients with multivessel disease the superiority of an Optical Coherence Tomography (OCT)-guided revascularization completion as compared to a standard angiography-guided revascularization completion by assessing:
- Post-procedural Minimal Stent Area (MSA)

Het eerste primaire doel van deze Open-label, Gerandomiseerde, Gecontroleerde Klinische Studie is om de non-inferoriteit van een op Prasugrel gebaseerde korte DAPT (30-45 dagen) aan te tonen, gevolgd door 11 maanden Prasugrel monotherapie versus standaard DAPT-regime door te beoordelen:
- Incidentie van Netto Adverse Clinical Events(NACE) 11 maanden na DAPT randomisatie als samengesteld eindpunt van dood, MI, beroerte of BARC bloeding 3 of 5

Het co-primaire doel is om bij patiënten met meervatslijden de superioriteit aan te tonen van een optical coherence tomography (OCT)-geleide volledige revascularisatie in vergelijking met een standaard angiografie-geleide revascularisatie door te beoordelen:
- Post-procedureel minimaal stentgebied (MSA)

E.5.1.1

Timepoint(s) of evaluation of this end point

11 months after DAPT randomisation

11 maanden na DAPT randomisatie

E.5.2

Secondary end point(s)

With respect to the antithrombotic therapy analysis, the secondary exploratory objectives primarily include the assessment of the primary endpoint for superiority if non-inferiority is demonstrated and the assessment of differences between the two antithrombotic regimens compared in the trial for the following endpoints (key secondary endpoints):
• Composite of major adverse cardiac and cerebrovascular events (MACCE) defined as cardiovascular death, myocardial infarction, or ischaemic stroke
• BARC type 3 or 5 events

With respect to the imaging-based analysis, the secondary exploratory objectives include the assessment of differences between OCT- and angiography-guided revascularization completion in terms of 12-month target vessel failure (TVF), defined as the composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target vessel revascularization.
In the subgroup of patients with multivessel disease, the interaction between antithrombotic therapy regimens (i.e. short DAPT followed by Prasugrel monotherapy versus standard DAPT) and the type of guidance to achieve revascularization completeness (i.e., OCT- versus angiography-guided) for the primary and key secondary endpoints will be formally explored by Cox proportional hazards regression models including the two factors as covariates alongside their interaction term.

Met betrekking tot de analyse van antitrombotische therapie omvatten de secundaire verkennende doelstellingen voornamelijk de beoordeling van het primaire eindpunt voor superioriteit als non-inferioriteit is aangetoond en de beoordeling van verschillen tussen de twee antitrombotische regimes die in het onderzoek werden vergeleken voor de volgende eindpunten (belangrijkste secundaire eindpunten):
• Samengesteld eindpunt van MACCE gedefinieerd als cardiovasculaire sterfte, MI of beroerte
• Incidentie van bloeding BARC 3 of 5 voorvallen

Met betrekking tot de op beeldvorming gebaseerde analyse, omvatten de secundaire verkennende doelstellingen de beoordeling van verschillen tussen OCT- en angiografie-geleide revascularisatie in termen van 12-maanden doelvatfalen (TVF), gedefinieerd als de samenstelling van cardiovasculaire dood, doelvat myocardinfarct, of ischemie-gedreven revascularisatie van het doelvat.
In de subgroep van patiënten met meervatslijden zal de interactie tussen antitrombotische therapieregimes (d.w.z. korte DAPT gevolgd door Prasugrel monotherapie versus standaard DAPT) en het type geleiding tot volledige revascularisatie (d.w.z. OCT- versus angiografie-geleide) voor de primaire en belangrijke secundaire eindpunten formeel worden onderzocht door Cox-propotional hazard regressie modellen, inclusief de twee factoren als co-variaties en hun interactie-term.

E.5.2.1

Timepoint(s) of evaluation of this end point

1 of 3 jaar na enrolment

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

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

12 maanden DAPT (volgens de huidige richtlijnen voor ACS patiënten)

12 months DAPT ( as per the current guidelines for ACS patients)

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

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:

828

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

828

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

Yes

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

450

F.4.2

For a multinational trial

F.4.2.1

In the EEA

1656

F.4.2.2

In the whole clinical trial

1656

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

geen

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

2022-05-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-07-05

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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