Clinical Trials Register

Summary
EudraCT Number:	2018-004446-42
Sponsor's Protocol Code Number:	MB11-2018
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:	2021-01-21
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

2018-004446-42

A.3

Full title of the trial

Maintenance Of aNtiplatElet Therapy in patients with coronary stenting undergoing surgery

Mantenimento della terapia antiaggregante nei pazienti portatori di stent coronarico candidati a chirurgia

A.3.1

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

Maintenance Of aNtiplatElet Therapy in patients with coronary stenting undergoing surgery

Mantenimento della terapia antiaggregante nei pazienti portatori di stent coronarico candidati a chirurgia

A.3.2

Name or abbreviated title of the trial where available

MONET BRIDGE

A.4.1

Sponsor's protocol code number

MB11-2018

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	AZIENDA SANITARIA OSPEDALIERA S.CROCE E CARLE CUNEO
B.1.3.4	Country	Italy
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	Chiesi Farmaceutici S.p.A.
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	Fondazione GISE Onlus
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Advice Pharma Group Srl
B.5.2	Functional name of contact point	Clinical Operation
B.5.3	Address:
B.5.3.1	Street Address	via Giovanni Durando 38/A
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20158
B.5.3.4	Country	Italy
B.5.4	Telephone number	0223997114
B.5.5	Fax number	0232066961
B.5.6	E-mail	giuseppe.terpolilli@advicepharma.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	Kengrexal 50 mg polvere per concentrato per soluzione per iniezione/infusione
D.2.1.1.2	Name of the Marketing Authorisation holder	Si segnala che l'AIC del farmaco Kengrexal non è quella di seguito bensì la seguente: 044016018 dell
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Cangrelor
D.3.2	Product code	[CANGRELOR. Si segnala che il codice ATC di seguit
D.3.4	Pharmaceutical form	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	163706-06-7
D.3.9.2	Current sponsor code	Cangrelor
D.3.9.3	Other descriptive name	Si segnala che il campo D.3.8.1 è stato volutamente indicato come SI, nonostante sia vero il contrario. E' stato fatto ciò per ovviare all'assenza nel databse dell'OsSC del INN approvato per il farmaco in oggetto, che risulta errere CANGRELOR.
D.3.9.4	EV Substance Code	SUB26448
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	50
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Solvent for parenteral use
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients a least 18 years of age on DAPT per standard of care who are planned to undergo non deferrable cardiac and non cardiac surgery which will require discontinuation of a P2Y12 inhibitor. Subjects with stent implantation within 12 months of an ACS and within 6 months of elective stent implantation for stable CAD, or subjects subjected to elective PCI within the previous 12 months if still in DAPT because considered high-risk thrombotic will be included.

Pazienti di almeno 18 anni di età in trattamento con DAPT, candidati a chirurgia non differibile (cardiaca o non cardiaca) che richiedano la sospensione perioperatoria dell’inibitore P2Y12. Verranno inclusi soggetti con impianto di stent entro 12 mesi da una sindrome coronarica acuta e entro 6 mesi dall’impianto elettivo di stent per coronaropatia stabile, o soggetti sottoposti a PCI elettiva entro i 12 mesi precedenti se ancora in DAPT perchè considerati ad alto rischio trombotico.

E.1.1.1

Medical condition in easily understood language

Patients a least 18 years of age on DAPT per standard of care who are planned to undergo non deferrable cardiac and non cardiac surgery which will require discontinuation of a P2Y12 inhibitor.

Pazienti di almeno 18 anni di età in trattamento con DAPT, candidati a chirurgia non differibile (cardiaca o non cardiaca) che richiedano la sospensione perioperatoria dell’inibitore P2Y12.

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	HLGT
E.1.2	Classification code	10011082
E.1.2	Term	Coronary artery 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 primary efficacy objective of this study is to demonstrate that a cangrelor infusion will maintain levels of residual platelet reactivity (PRU < 208) as measured by Accriva VerifyNow® P2Y12 assay.
The main safety objective is to demonstrate that patients receiving cangrelor infusion before cardiac and non cardiac surgery have an acceptable safety profile and can undergo surgery without excessive bleeding peri-operatively.

La percentuale di pazienti con PRU < 208, come determinato mediante Accriva VerifyNow® P2Y12, misurato durante l'infusione del farmaco prima dell'intervento chirurgico.
Il principale obiettivo di sicurezza dello studio è quello di dimostrare che i pazienti che ricevono un’infusione di cangrelor prima di un intervento di chirurgia cardiaca o non-cardiaca, hanno un profilo di sicurezza accettabile e possono essere sottoposti a intervento chirurgico senza sanguinamento perioperatorio eccessivo.

E.2.2

Secondary objectives of the trial

The absence of excessive surgery-related bleeding, defined as the occurrence of bleeding events of Bleeding Academic Research Consortium (BARC)25 grade = 3 in patients undergoing non cardiac surgery and BARC = 4 in patients undergoing cardiac surgery or with the need for re-intervention within 24 hours of discontinuation of the study drug.
In addition, ischemic endpoints (death, myocardial infarction, defined and probable stent thrombosis) and hemorrhages (as previously defined) will be evaluated up to a 30-day follow-up and detailed analysis of platelet reactivity data in the different phases of the period surgical.

L'assenza di sanguinamenti correlati a chirurgia, definiti come Bleeding Academic Research Consortium (BARC) di grado = 3 in pazienti sottoposti a chirurgia non cardiaca e BARC= 4 in pazienti sottoposti a chirurgia cardiaca o con necessità di re-intervento entro 24 ore dalla sospensione del farmaco in studio.
Verranno inoltre valutati endpoint ischemici (morte, infarto miocardico, trombosi di stent definita e probabile) e emorragici (come già precedentemente definiti) sino a un follow up di 30 giorni e eseguite analisi dettagliate dei dati di reattività piastrinica nelle diversi fasi del period peri-chirurgico.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Provide written informed consent before initiation of any study related procedures;
2. be = 18 years of age;
3. have received any dose of a P2Y12 inhibitor (clopidogrel, ticlopidine, prasugrel, or ticagrelor) at any dose within at least 48 hours prior to randomization;
4. patients undergoing non deferrable cardiac or non cardiac surgery which requires discontinuation of P2Y12 inhibitor due to a significant bleeding risk.
5. Female subject of potential child-bearing should have a negative pregnancy test (preferably serum hCG pregnancy test) at screening.

1. I pazienti devono fornire il consenso informato scritto prima di iniziare qualsiasi procedure relativa allo studio;
2. età =18 anni;
3. pazienti che abbiano ricevuto un inibitore P2Y12 (clopidogrel, ticlopidina, prasugrel, o ticagrelor) entro le 48 ore precedenti la randomizzazione;
4. pazienti candidati a chirurgia non differibile (cardiaca e non cardiaca) che richiedano la sospensione perioperatoria dell’inibitore P2Y12 per l’elevato rischio emoragico peri-procedurale.
5. I soggetti di sesso femminile potenzialmente fertili dovrebbero avere un test di gravidanza negativo (preferibilmente un test di gravidanza con siero hCG) durante lo screening.

E.4

Principal exclusion criteria

1. Active bleeding with evident contraindications to DAPT
2. Patients requiring oral anticoagulant therapy
3. PCI within 1 month
4. Intracranial neoplasm or history of intracranial surgery
5. History of bleeding diathesis
6. Thrombocytopenia (platelet count of less than 100,000/µL)
7. Known International Normalized Ratio (INR) greater than 1.5 at screening.
8. Requirement for dialysis treatment (hemodialysis or peritoneal)
9. Estimated Glomeular filtration rate eGFR <30 ml/min
10. Administration of abciximab within 24 hours of randomization or administration of eptifibitide or tirofiban within 12 hours of randomization
11. Plans to continue oral anticoagulant or P2Y12 inhibitors or cangrelor in the pre-operative period
12. Refusal to receive blood transfusion
13. Receipt of fibrinolytic therapy in the 12 hours preceding randomization
14. Allergy, hypersensitivity, or contraindication to cangrelor, mannitol, sorbitol, or microcrystalline cellulose
15. High likelihood of being unavailable for follow-up
16. Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of randomization
17. Confirmed of suspected pregnancy (if woman of child-bearing potential) or lactating females confirmed. Pregnancy status must be confirmed by serum or urine test (preferably by a serum hCG pregnancy test)
18. Any disease or condition which, in the judgment of the investigator, would place the patient at undue risk by being enrolled in the trial

1. sanguinamento attivo con evidente controindicazione a DAPT;
2. indicazione a concomitante terapia anticoagulante orale;
3. PCI entro il primo mese;
4. neoplasia intracranica o storia di chirurgia intracranica;
5. storia di diatesi emorragica;
6. trombocitopenia (conta piastrinica inferiore a 100,000/µL);
7. International Normalized Ratio (INR) maggiore di 1.5 al momento dello screening;
8. concomitante trattamento dialitico (emodialisi o dialisi peritoneale);
9. filtrato glomerulare stimato <30 ml/min;
10. precedente somministrazione di abciximab entro le precedenti 24 ore prima della randomizzazione o di eptifibitide o tirofiban nelle 12 ore antecedenti la randomizzazione;
11. pianificata terapia con anticoagulante orale, cangrelor o inibitore P2Y12 nel periodo perioperatorio;
12. rifiuto di ricevere trasfusioni ematiche;
13. terapia fibrinolitica nelle 12 ore antecedenti la randomizzazione;
14. allergia, ipersensibilità o controindicazioni a cangrelor, mannitolo, sorbitolo, o cellulosa microcristallina;
15. elevata probabilità di essere perso al follow up;
16. partecipazione ad altro studio clinico che coinvolga la valutazione di altro farmaco in sperimentazione o device entro i precedenti 30 giorni prima della randomizzazione;
17. conferma di una gravidanza sospetta (se donna con potenziale fertile) o donne attualmente in allattamento. Lo stato di gravidanza deve essere confermato da un test sierico o urinario (preferibilmente da un test sierico di gravidanza hCG).
18. qualunque condizione clinica che, a giudizio dello sperimentatore, ponga il paziente a rischio proibitivo nel momento in cui venga arruolato nel trial.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the percentage of patients with PRU < 208 for all samples assessed during study drug infusion prior to surgery as determined by VerifyNow® P2Y12 point of care assay measured during study drug infusion prior to surgery.

La percentuale di pazienti con PRU < 208, come determinato mediante Accriva VerifyNow® P2Y12, misurato durante l’infusione del farmaco prima dell’intervento chirurgico.

E.5.1.1

Timepoint(s) of evaluation of this end point

The study drug will be measured during study drug infusion prior to surgery.

Misurato durante l’infusione del farmaco prima dell’intervento chirurgico.

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

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

Yes

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

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

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

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

140

F.4.2

For a multinational trial

F.4.2.1

In the EEA

140

F.4.2.2

In the whole clinical trial

140

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)

N.A.

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

2019-05-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-06-20

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

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