Clinical Trials Register

Summary
EudraCT Number:	2017-003836-35
Sponsor's Protocol Code Number:	COP-AF
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:	2020-10-07
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2017-003836-35

A.3

Full title of the trial

COlchicine For The Prevention Of Perioperative Atrial Fibrillation In Patients Undergoing Thoracic Surgery

A.3.1

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

The Prevention Of Perioperative Atrial Fibrillation In Patients Undergoing Thoracic Surgery

Prevenzione della fibrillazione atriale perioperatoria in chirurgia toracica

A.3.2

Name or abbreviated title of the trial where available

COP-AF

A.4.1

Sponsor's protocol code number

COP-AF

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	Population Health Research Institute
B.1.3.4	Country	Canada
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	HAMILTON HEALTH SCIENCES CORPORATION
B.4.2	Country	Canada
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	IRCCS OSPEDALE SAN RAFFAELE
B.5.2	Functional name of contact point	Anestesia e Rianimazione Cardio-Tor
B.5.3	Address:
B.5.3.1	Street Address	Via Olgettina, 60
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20132
B.5.3.4	Country	Italy
B.5.4	Telephone number	0226436155
B.5.5	Fax number	0226436152
B.5.6	E-mail	landoni.giovanni@hsr.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.2.1.1.1	Trade name	COLCHICINE TIOFARMA 0.5mg tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	TIOFARMA BV
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.3.1	Product name	colchicine 0.5mg
D.3.2	Product code	[RVG21347]
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	IU/mg international unit(s)/milligram
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	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.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	COLCHICINE TIOFARMA 0.5mg tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	TEVA NEDERLAND BV
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.3.1	Product name	COLCHICINE 0.5MG
D.3.2	Product code	[RVG34100]
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	IU/mg international unit(s)/milligram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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	IU/mg international unit(s)/milligram
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	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	Capsule, soft
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	Capsule, soft
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

Perioperative atrial fibrillation / atrial flutter after thoracic surgery

profilassi fibrillazione atriale perioperatoria in pazienti sottoposti a chirurgia toracica maggiore

E.1.1.1

Medical condition in easily understood language

Perioperative atrial fibrillation / atrial flutter after thoracic surgery

profilassi fibrillazione atriale perioperatoria in pazienti sottoposti a chirurgia toracica maggiore

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	10003658
E.1.2	Term	Atrial fibrillation
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 objective of this trial is to determine whether the administration of colchicine compared with placebo reduces the occurrence of perioperative atrial fibrillation / atrial flutter (AF) within 14 days of randomization.

determinare se la somministrazione di colchicina comparata al placebo riduca l’incidenza di fibrillazione atriale / flutter atriale perioperatori nei 14 giorni di randomizzazione nei pazienti sottoposti a chirurgia toracica maggiore.

E.2.2

Secondary objectives of the trial

The secondary trial objectives are to determine whether the administration of colchicine compared with placebo reduces the:
1. first occurrence of the composite of all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke within 14 days of randomization;
2. duration of stay in ICU, step-down, and in-hospital;
3. all-cause mortality within 14 days of randomization;
4. occurrence of myocardial infarction within 14 days of randomization.
5. occurrence of myocardial injury after noncardiac surgery;

Obiettivi secondari: determinare come la somministrazione di colchicina comparata al placebo impatta sui seguenti outcome:
1. outcome composito di mortalità per qualsiasi causa, infarto miocardico non fatale, stroke non fatale entro 14 giorni dalla randomizzazione
2. durata di ricovero in terapia intensiva, ricovero in unità subintensiva e ricovero in ospedale
3. mortalità per qualsiasi causa entro 14 giorni dalla randomizzazione
4. infarto miocardico entro 14 giorni dalla randomizzazione
5. danno miocardico post chirurgia non cardiaca (miocardial injury after noncardiac surgery, MINS)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

All patients undergoing thoracic surgery with general anesthesia are eligible for the trial if they are =55 years of age at the time of randomization and expected to require at least an overnight hospital
admission after surgery.

Pazienti sottoposti a chirurgia toracica in anestesia generale di età = 55 anni al momento della randomizzazione, se prevista almeno una notte di ricovero in ospedale dopo la chirurgia.

E.4

Principal exclusion criteria

1. patients with a prior history of documented AF;
2. patients currently taking anti-arrhythmic medication other than ß-blockers, calcium channels blockers or digoxin;
3. patients undergoing minor thoracic interventions/procedures (i.e., minor chest-wall surgeries, chest tube insertions, or needle pleural/lung biopsies);
4. patients with contraindications to colchicine (i.e., allergy to colchicine, myelodysplastic disorders, or an estimated glomerular filtration rate [eGFR] <30 mL/min/1.73m);
5. patients not expected to take oral medications for >24 hours after surgery (e.g., esophagectomy);
6. patients scheduled for lung transplantation;
7. patients currently taking non-study colchicine before surgery;
8. patients with severe hepatic dysfunction;
9. patients with aplastic anemia;
10. women of childbearing potential who are not taking effective contraception, pregnant or breast-feeding;
11. patients who took within the last 14 days or scheduled to take during the first 10 days after surgery clarithromycin, erythromycin, telithromycin, cyclosporine, ketoconazole, or itraconazole during the
first 10 days after surgery; OR
12. HIV patients treated with antiretroviral therapy;

1. Pazienti con anamnesi pregressa di FA documentabile;
2. Pazienti in terapia con farmaci anti aritmici esclusi beta bloccanti, calcio antagonisti o digossina;
3. Pazienti sottoposti a procedure/interventi chirurgici toracici minori (es.chirurgia minore della parete toracica, inserzione di drenaggio toracico, agobiopsie della pleura/polmone);
4. Pazienti con controindicazioni all’assunzione di colchicina (ovvero: allergia alla colchicina, disordini mielodisplastici, velocità di filtrazione glomerulare stimata (eGFR < 30 mL/min/1.73m2))
5. Pazienti non in grado di assumere terapia orale per > 24h post chirurgia (es. esofagectomie)
6. Pazienti in lista per trapianto di polmone
7. Pazienti già in terapia con colchicina (non legata a questo studio) prima della chirurgia
8. Pazienti con severa disfuzione epatica
9. Pazienti con anemia aplastica
10. Donne in età potenzialmente fertile che non utilizzano adeguati metodi contraccettivi, donne gravide o che allattano.
11. Pazienti che assumeranno nei 10 giorni post chirurgia o che hanno assunto nei 14 giorni precedenti i seguenti farmaci: telitromicina, ciclosporina, ketoconazolo o itroconazolo; o
12. Pazienti HIV positivi in terapia antiretrovirale

E.5 End points

E.5.1

Primary end point(s)

Clinically important perioperative atrial fibrillation, defined as atrial fibrillation developing after randomization until the end of follow-up, and that results in angina, heart failure, symptomatic hypotension, or that
requires treatment with a rate controlling drug, antiarrhythmic drug or electrical cardioversion.

E.5.1.1

Timepoint(s) of evaluation of this end point

Evaluation at 14 days after randomization.

14 giorni dopo la randomizzazione

E.5.2

Secondary end point(s)

1. first occurrence of the composite of all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke within 14 days of randomization;
2. occurrence of myocardial injury after noncardiac surgery;
3. number of days alive and at home;
4. time to chest tube removal within 14 days of randomization.
5. duration of stay in ICU, step-down, and in-hospital;
6. all-cause mortality within 14 days of randomization; and
7. occurrence of myocardial infarction within 14 days of randomization

Determinare come la somministrazione di colchicina comparata al placebo impatta sui seguenti outcome:
1. outcome composito di mortalità per qualsiasi causa, infarto miocardico non fatale, stroke non fatale entro 14 giorni dalla randomizzazione
2. verificarsi danno miocardico post chirurgia non cardiaca (miocardial injury after noncardiac surgery, MINS)
3. numero di giorni in vita e a domicilio;
4. tempo necessario per la rimozione di drenaggio toracico entro 14 giorni dalla randomizzazione;
5. durata del ricovero in terapia intensiva, ricovero in unità subintensiva e ricovero in ospedale;
6. mortalità per qualsiasi causa entro 14 giorni dalla randomizzazione;
7. verificarsi di infarto miocardico entro 14 giorni dalla randomizzazione.

E.5.2.1

Timepoint(s) of evaluation of this end point

Evaluation at 14 days after randomization

14 giorni dopo la randomizzazione

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)

Yes

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

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

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

Information not present in EudraCT

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

Australia

Austria

Belgium

Canada

Germany

Hong Kong

Hungary

Italy

Malaysia

Netherlands

Pakistan

Poland

Russian Federation

South Africa

Spain

Switzerland

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

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:

980

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

1820

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

430

F.4.2

For a multinational trial

F.4.2.1

In the EEA

800

F.4.2.2

In the whole clinical trial

2800

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)

Good Clinical Practice

Normale Pratica Clinica

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

2020-07-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-03-04

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials