Clinical Trials Register

Summary
EudraCT Number:	2019-004374-25
Sponsor's Protocol Code Number:	61528
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:	2021-05-24
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

2019-004374-25

A.3

Full title of the trial

Thoracic duct identification with Indocyanine green fluorescence during minimally invasive esophagectomy with patient in prone position

Identificazione del dotto toracico mediante l'utilizzo del verde d'indocianina nei pazienti sottoposti ad esofagectomia mininvasiva in posizione prona

A.3.1

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

Identification of the thoracic duct using a vital dye in patients undergoing minimally invasive esophagectomy

Identificazione del dotto toracico mediante l'utilizzo di un colorante vitale nei pazienti sottoposti ad intervento mininvasivo di esofagectomia

A.3.2

Name or abbreviated title of the trial where available

VERDEDT

A.4.1

Sponsor's protocol code number

61528

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 OSPEDALIERO-UNIVERSITARIA UDINE
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	Segreteria tecnico-scientifica Comitato Etico Unico Regionale (C.E.U.R.) del Friuli-Venezia Giulia
B.5.2	Functional name of contact point	Direzione Scientifica IRCCS Centro
B.5.3	Address:
B.5.3.1	Street Address	Via F. Gallini, 2
B.5.3.2	Town/ city	AVIANO (PN)
B.5.3.3	Post code	33081
B.5.3.4	Country	Italy
B.5.4	Telephone number	0434659915
B.5.6	E-mail	chiara.presacco@cro.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	VERDE INDOCIANINA PULSION - 5MG/ML POLVERE PER SOLUZIONE INIETTABILE 5 FLACONCINI DI VETRO CONTENENTI 25 MG DI POLVERE
D.2.1.1.2	Name of the Marketing Authorisation holder	PULSION MEDICAL SYSTEMS AG
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	Verdye
D.3.2	Product code	[01]
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intralymphatic use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	VERDE INDOCIANINA
D.3.9.1	CAS number	3599-32-4
D.3.9.2	Current sponsor code	61528
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
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	Yes
D.3.11.13.1	Other medicinal product type	colorante vitale

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

Chylothorax is a serioso post-operative complication, which occurs in 2-12% of patients undergoing esophagectomy. Thoracic duct lesion leads to a reduction of body fluids and albumin resulting in hypovolemia, also delays oral food intake, increase hospital stay and negatively affects overall survival. It is also associated with pneuomonia resulting in difficulty breathing, which also determines an increased risk of sepsis.

Il chilotorace è una grave complicanza post-operatoria, che si verifica nel 2-12% dei pazienti sottoposti a esofagectomia. La lesione del dotto toracico porta ad una riduzione dei fluidi corporei e dell'albumina con conseguente ipovolemia, inoltre ritarda l'assunzione orale di cibo, aumenta la degenza ospedaliera e influisce negativamente sulla sopravvivenza globale. E' anche associato a polmonite con conseguente difficoltà respiratoria, che determina anche un aumento del rischio di sepsi.

E.1.1.1

Medical condition in easily understood language

The chylothorax, often caused by a lesion of the thoracic duct, is the presence of an abnormal collection of lymphatic fluid in the pleural cavity, or the space that surrounds the lung.

Il chilotorace, spesso determinato da una lesione del dotto toracico, è la presenza di una raccolta anormale di liquido linfatico nel cavo pleurico, ovvero lo spazio che circonda il polmone.

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04]

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	10051228
E.1.2	Term	Chylothorax
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal 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 aim of the study is to demonstrate the feasibility to use near infrared (NIR) fluorescence guided thoracoscopy to identify the thoracic duct anatomy and check for intraoperative lesions during minimally invasive esophagectomy.

Obiettivo primario dello studio è quello di valutare se l’uso del verde d'indocianina (ICG) in toracoscopia durante l’esofagectomia permette l’identificazione intraoperatoria del dotto toracico e di sue eventuali lesioni.

E.2.2

Secondary objectives of the trial

The incidence of adverse reactions, pain, iatrogenic injury and / or complications at the site of ICG injection.

Valutare l’incidenza di reazioni avverse, dolore, lesioni iatrogene e/o complicanze nel sito di iniezione di ICG.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients aged 18 or over
2. American Society of Anesthesiologists’ (ASA) class I, II or III;
3. Elective surgery patients;
4. Patients’ written acceptance to be included in the study.

1. Pazienti=18 anni con diagnosi di neoplasia dell'esofago o della giunzione gastro esofagea sottoposti a esofagectomia toracoscopica.
2. Classe I, II o III dell'American Society of Anesthesiologists (ASA)
3. Chirurgia elettiva
4. Capacità di esprimere il consenso informato alla partecipazione allo studio

E.4

Principal exclusion criteria

1. Class IV-V of the American Society of Anesthesiologists (ASA)
2. Patients with hyperthyroidism and / or autoimmune adenomas of the thyroid
3. Allergy to contrast medium, hypersensitivity to iodine, indocyanine green or sodium iodide.
4. Patients who cannot undergo transthoracic esophagectomy
5. Pregnancy or breastfeeding or positive pregnancy test (to be performed in potentially fertile women)
6. Severe kidney failure (estimated GFR <30 mL / min / 1.73 m2 at the time of screening)
7. Participation in a clinical study in which an experimental drug was administered within 30 days or 5 half-lives of the study drug
8. Any clinical condition that in the investigator's judgment would make the patient unsuitable for the study
9. Patients who refuse to give their written consent to participate in the study

1. Classe IV-V dell'American Society of Anesthesiologists (ASA)
2. Pazienti con ipertiroidismo e/o adenomi autoimmuni della tiroide
3. Allergia al mezzo di contrasto, ipersensibilità allo iodio, al verde d’indocianina o allo ioduro di sodio.
4. Pazienti che non possono essere sottoposti a esofagectomia transtoracica
5. Gravidanza o allattamento o test di gravidanza positivo (da eseguire nelle donne potenzialmente fertili)
6. Grave insufficienza renale (GFR stimata < 30 mL/min/1,73 m2 al momento dello screening)
7. Partecipazione ad uno studio clinico in cui è stato somministrato un farmaco sperimentale entro 30 giorni o 5 emivite del farmaco in studio
8. Qualsiasi condizione clinica che a giudizio dello sperimentatore renderebbe il paziente non idoneo per lo studio
9. Pazienti che rifiutano di dare il proprio consenso scritto alla partecipazione allo studio

E.5 End points

E.5.1

Primary end point(s)

This study intends to demonstrate the feasibility of using indocyanine green in thoracoscopy guided by near-infrared fluorescence (NIR) to identify the TD anatomy and verify the presence of intraoperative lesions during minimally invasive esophagectomy.

Questo studio intende di dimostrare la fattibilità dell’utilizzo del verde d’indocianina in toracoscopia guidata dalla fluorescenza nel vicino infrarosso (NIR) per identificare l’anatomia del dotto toracico e verificare la presenza di lesioni intraoperatorie durante l’esofagectomia mininvasiva.

E.5.1.1

Timepoint(s) of evaluation of this end point

The timepoints of evaluation of this end point is represented by the surgical time for thoracoscopic esophagectomy

Il tempo di rilevazione è rappresentato dal tempo chirurgico per l'intervento di esofagectomia toracoscopica

E.5.2

Secondary end point(s)

Evaluate the incidence of adverse reactions, pain, iatrogenic injury and / or complications at the site of ICG injection.

Valutare l’incidenza di reazioni avverse, dolore, lesioni iatrogene e/o complicanze nel sito di iniezione di ICG.

E.5.2.1

Timepoint(s) of evaluation of this end point

From the end of the VERDEDT procedure to the discharge of the patient undergoing oesophagectomy.

Dalla fine della procedura VERDEDT alla dimissione del paziente sottoposto ad esfoagectomia

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

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)

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

E.8.1.1

Randomised

E.8.1.2

Open

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

Yes

E.8.1.7.1

Other trial design description

studio interventistico con disegno a singolo braccio

interventional study with single-arm design

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

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

After nutritional assessment and adequate resumption of oral feeding, the patient will be discharged and only in this case will the path of that patient end within the study.
The end of the study will coincide with the last discharge of the last patient enrolled.

Dopo valutazione nutrizionale e adeguata ripresa dell’alimentazione per os il paziente verrà dimesso e solo in questo caso terminerà il percorso di quel paziente all’interno dello studio.
La fine dello studio coinciderà con l’ultima dimissione dell’ultimo paziente arruolato.

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

The method used to visualize the thoracic duct does not modify the diagnostic therapeutic pathway of patients with esophageal neoplasia. The program for the treatment or assistance of the subjects at the end of their participation in the study foresees a radiological control of the gastro-oesophageal anastomosis by means of rx digestive tract with subsequent and gradual recovery of the oral feeding after visit of the dietitian.

La metodica utilizzata per la visualizzazione del dotto toracico non modificare il percorso diagnostico terapeutico dei pazienti con neoplasia dell'esofago. Il programma per il trattamento o l'assistenza dei soggetti al termine della loro partecipazione allo studio prevede un controllo radiologico dell'anastomosi gastro-esofagea mediante rx tubo digerente con successiva e graduale ripresa dell'alimentazione per via orale dopo visita della dietista.

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

2020-03-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-12-17

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

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