Clinical Trials Register

Summary
EudraCT Number:	2021-000637-13
Sponsor's Protocol Code Number:	CRAP-ACStrial
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:	2021-10-19
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

2021-000637-13

A.3

Full title of the trial

Cardiac and renal protective effect of colchicine early on-admission administered in patient with acute coronaric syndrome in treatment with atorvastatin

Effetto cardio- e nefro-protettivo della colchicina somministrata early on-admission nei pazienti con sindrome coronarica acuta che ricevono atorvastatina

A.3.1

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

Colchicine protective effect on heart and kidney in patients wiyh coronaric syndrome in treatment with atorvastatin

Effetto protettivo su cuore e reni della colchicina amministrata in pazienti con sindrome coronarica acuta che ricevono atorvastatina

A.3.2

Name or abbreviated title of the trial where available

CRAP-ACS trial

A.4.1

Sponsor's protocol code number

CRAP-ACStrial

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 USL TOSCANA CENTRO
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Istituto di Ricerche Farmacologiche Mario Negri IRCCS di Milano
B.5.2	Functional name of contact point	Unità Project Management
B.5.3	Address:
B.5.3.1	Street Address	Via Mario Negri, 2
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20156
B.5.3.4	Country	Italy
B.5.4	Telephone number	0239014661
B.5.6	E-mail	irene.desimone@marionegri.it

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	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	Colchicina
D.3.2	Product code	[M04AC01]
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	COLCHICINA
D.3.9.2	Current sponsor code	NA
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	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	atorvastatina
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	Atorvastatina
D.3.2	Product code	[atorvastatina]
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	ATORVASTATINA
D.3.9.2	Current sponsor code	atorvastatina
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	80
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

sindrome coronarica acuta (ACS) statin-naive con indicazione ad una strategia invasiva di rivascolarizzazione che vengono ricoverati in reparto cardiologico.

E.1.1.1

Medical condition in easily understood language

sindrome coronarica acuta

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	PT
E.1.2	Classification code	10051592
E.1.2	Term	Acute coronary syndrome
E.1.2	System Organ Class	10007541 - Cardiac disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10051592
E.1.2	Term	Acute coronary syndrome
E.1.2	System Organ Class	10007541 - Cardiac disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10051592
E.1.2	Term	Acute coronary syndrome
E.1.2	System Organ Class	10007541 - Cardiac disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10051592
E.1.2	Term	Acute coronary syndrome
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

L’obiettivo primario è confrontare l’effetto antiinfiammatorio acuto del trattamento con colchicina in associazione alla terapia farmacologica standard impiegata nelle sindromi coronariche acute (che prevede anche statine ad alta intensità) rispetto alla sola terapia farmacologica standard sul rialzo degli indici di infiammazione (hsCRP) correlato con l’evento coronarico e con la procedura di rivascolarizzazione percutanea.

E.2.2

Secondary objectives of the trial

Un obiettivo secondario è valutare se l’effetto antiinfiammatorio acuto si traduce in un beneficio clinico evidenziabile con una riduzione degli eventi avversi durante ricovero e durante il periodo di follow-up. Un altro obiettivo pre-specificato è rappresentato dalla valutazione della tollerabilità della colchicina nella popolazione dei pazienti con ACS che afferiscono ai nostri ospedali.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Sono elegibili per lo studio tutti i pazienti di età = 18 anni con sindrome coronarica acuta (ACS) statin-naive con indicazione ad una strategia invasiva di rivascolarizzazione che vengono ricoverati in reparto cardiologico.

E.4

Principal exclusion criteria

- Terapia precedente con statine o con colchicina in cronico per altre condizioni mediche
- precedente o prevista somministrazione di altre terapie immunosoppressive
- grave insufficienza epatica
- grave insufficienza renale
- malignità nota attiva
- grave insufficienza cardiaca - definita come insufficienza ventricolare sinistra con classe NYHA = 3 o classe Killip = 2 o quadro di shock cardiogeno alla presentazione;
- grave insufficienza gastrointestinale acuta o cronica – definita da nausea, vomito, diarrea, malattie da malassorbimento, quadro di malnutrizione;
- stato di gravidanza o di allattamento. Per i soggetti di sesso femminile in età pre-menopausale lo stato di gravidanza viene escluso con test sierico;
- Qualsiasi condizione medica o valore di laboratorio clinicamente significativo che possa presentare un rischio per la sicurezza o interferire con la conformità allo studio e con il follow-up o confondere l’interpretazione dei dati per tutto il periodo dello studio
- diagnosi confermata di COVID-19
- Partecipazione ad uno studio clinico in cui sia stato somministrato un farmaco sperimentale nei 30 giorni precedenti

E.5 End points

E.5.1

Primary end point(s)

confrontare l’effetto del trattamento con colchicina in associazione alla terapia standard (che include la statina ad alta intensità, per questo studio atorvastatina 80 mg) rispetto al solo trattamento con terapia standard in termini di rialzo relativo della hsCRP tra il valore basale (all’ingresso) e quello alla dimissione.

E.5.1.1

Timepoint(s) of evaluation of this end point

Tempo intercorso tra ammissione in reparto e dimissione (in media 4 giorni)

E.5.2

Secondary end point(s)

valori di picco del CK-MB nelle prime 72 ore dopo l’ingresso;
la percentuale di pazienti con valori di hsCRP=2 mg/L dopo 30 giorni dall’evento indice (rischio infiammatorio residuo);; variazione del filtrato glomerulare a 30 giorni; l’incidenza combinata di eventi clinici avversi definiti come re-infarto, danno renale persistente (riduzione del filtrato glomerulare =25% rispetto al basale) o morte per tutte le cause nei 30 giorni successivi all’evento indice;; tollerabilità della terapia con colchicina valutata come percentuale di pazienti arruolati che completa il trattamento; incidenza di danno renale acuto (incremento della creatinina = 0.5 mg/dl o 25% rispetto al valore basale, nelle prime 72 ore);; variazione (valore assoluto e relativo) del filtrato glomerulare / creatinina tra l’ingresso e il picco durante il ricovero;

E.5.2.1

Timepoint(s) of evaluation of this end point

prime 72 ore dopo la randomizzazione; 30 giorni dalla randomizzazione; minimo 30 giorni dalla randomizzazione; data di dimissione dal reparto di cardiologia; 72 ore dalla randomizzazione; tempo intercorso tra inizio e fine ricovero ospedaliero

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

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

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)

Yes

E.8.2.2

Placebo

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:

100

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

175

F.4.2

For a multinational trial

F.4.2.1

In the EEA

175

F.4.2.2

In the whole clinical trial

175

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)

La durata dello studio è breve (periodo di ricovero ospedaliero) e la terapia viene somministrata dal personale infermieristico durante la degenza. Alla dimissione la colchicina viene interrotta mentre l’atorvastatina viene continuata secondo le raccomandazioni delle linee guida.

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

2021-10-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-02-08

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

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