Clinical Trials Register

Summary
EudraCT Number:	2021-001122-22
Sponsor's Protocol Code Number:	BLUEPAT_FNUSA_2021
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-03-18
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

Czechia - SUKL

A.2

EudraCT number

2021-001122-22

A.3

Full title of the trial

Subpleural lung nodules marking with blue dye substance and contrast agent under CT-guided control with subsequent videothoracoscopic wedge resection: prospective randomized study.

Značení subpleurálně uložených plicních ložisek substancí modrého barviva a kontrastní látky pod CT navigovanou kontrolou a jejich následná videotorakoskopická klínovitá resekce: prospektivní randomizovaná studie.

A.3.1

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

Resection of blue-marked lung nodules under CT control

Resekce modře značených plicních ložisek pod CT kontrolou

A.3.2

Name or abbreviated title of the trial where available

BLUEPAT

A.4.1

Sponsor's protocol code number

BLUEPAT_FNUSA_2021

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	Fakultní nemocnice u sv. Anny v Brně
B.1.3.4	Country	Czechia
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	Fakultní nemocnice u sv. Anny v Brně
B.4.2	Country	Czechia
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fakultní nemocnice u sv. Anny v Brně
B.5.2	Functional name of contact point	Oddělení klinických studií
B.5.3	Address:
B.5.3.1	Street Address	Pekařská
B.5.3.2	Town/ city	Brno
B.5.3.3	Post code	656 91
B.5.3.4	Country	Czechia
B.5.4	Telephone number	+420543185172
B.5.6	E-mail	trials.icrc@fnusa.cz

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	Patent Blue V Sodium Injection 2,5 % (25 mg/ml)
D.2.1.1.2	Name of the Marketing Authorisation holder	Guerbet France
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Patent Blue V Sodium Injection 2,5 %
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intrapleural use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SODIUM PATENT BLUE V
D.3.9.1	CAS number	20262-76-4
D.3.9.3	Other descriptive name	SODIUM PATENT BLUE V
D.3.9.4	EV Substance Code	SUB74466
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	25
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.2.1.1.1	Trade name	Omnipaque 350 mg I/ml injekční roztok
D.2.1.1.2	Name of the Marketing Authorisation holder	GE Healthcare AS
D.2.1.2	Country which granted the Marketing Authorisation	Czechia
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	Omnipaque mg l/ml
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intrapleural use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	IOHEXOL
D.3.9.1	CAS number	66108-95-0
D.3.9.4	EV Substance Code	SUB08228MIG
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	350
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	Yes
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

Focal pulmonary lesions

Ložiskové plicní léze

E.1.1.1

Medical condition in easily understood language

Focal pulmonary lesions

Ložiskové plicní léze

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	10077488
E.1.2	Term	Pulmonary resection
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Proof of the advantage of subpleural lung nodules marking.

Průkaz výhodnosti značení subpleurálně uložených plicních ložisek

E.2.2

Secondary objectives of the trial

1. Detailed characteristic of nodules
2. Marking method feasibility
3. Additional safety information

1. Bližší charakteristika ložisek
2. Proveditelnost metody značení
3. Doplňující bezpečnostní informace

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age ≥ 18 years
2. Subpleurally deposited pulmonary lesion(s) with the need for further histological diagnosis, which is/are:
2.1. located at a depth of 0 30 mm below the pleura
2.2. less than 40 mm
2.3. with growth progression according to Lung -RADS criteria (version 1.1)
2.4. clearly not infiltrating the parietal pleura according to CT examination
3. Cognitive fitness and medical condition of the patient enabling a full understanding of information about clinical trial and signing of informed consent
4. Participants in a clinical trial of childbearing potential must agree to the use of prescribed contraceptive methods for the duration of the following clinical trial:
4.1. Women - Proper use of a highly reliable method of contraception, ie combined hormonal contraceptives (in oral, vaginal, or transdermal dosage form), gestagen hormonal contraceptives associated with ovulation inhibition (in oral or injectable dosage form), non-hormonal intrauterine device, or hormone-releasing intrauterine device, ev. the presence of bilateral tubal occlusion, a partner's vasectomy, or adherence to sexual abstinence.
4.2. Men - Adherence to sexual abstinence or the use of an adequate contraceptive method (ie condom) in case of sexual intercourse.

1. Věk ≥ 18 let
2. Subpleurálně uložené/á plicní ložisko/ložiska s nutností další histologické diagnostiky, které/á je/jsou:
2.1. lokalizováno/a v hloubce od 0 30 mm pod pleurou
2.2. menší než 40 mm
2.3. s progresí růstu dle Lung -RADS kritérií (verze 1.1)
2.4 jednoznačně neinfiltrující parietální pleuru dle CT došetření
3. Kognitivní zdatnost a zdravotní stav pacienta umožňující plné porozumění informací o klinickém hodnocení a podpis informovaného souhlasu
4. Účastníci klinického hodnocení v plodném věku musí souhlasit s používáním předepsaných metod antikoncepce po dobu trvání tohoto klinického hodnocení:
4.1. Ženy – Správné použití vysoce spolehlivé antikoncepční metody, tj. kombinované hormonální antikoncepce (v perorální, vaginální nebo transdermální lékové formě), gestagenní hormonální antikoncepce spojené s inhibicí ovulace (v perorální nebo injekční lékové formě), nehormonálního nitroděložního tělíska nebo nitroděložního tělíska uvolňující hormony, ev. přítomnost oboustranné tubární okluze, vazektomie u partnera, nebo dodržování sexuální abstinence.
4.2. Muži – Dodržování sexuální abstinence nebo použití adekvátní antikoncepční metody (tj. kondomu) v případě pohlavního styku.

E.4

Principal exclusion criteria

1. Pregnancy or breast-feeding
2. History of hypersensitivity/allergy to patent blue or triphenylmethane dyes in medicinal products, food or cosmetics
3. Hypersensitivity/allergy or history of severe adverse reactions to iodine or iodine contrast agents (eg severe renal impairment following prior administration of an iodine contrast agent)
4. Hypersensitivity/allergy to excipients in investigated medical product
5. Hypersensitivity/allergy to trimecaine, or other local anesthetics
6. Manifest hyperthyroidism or thyrotoxicosis
7. Scheduled thyroid scan, thyroid function test, or radioiodine treatment

1. Těhotenství či kojení
2. Hypersenzitivita/alergie na patentní modř nebo trifenylmetanová barviva obsažená v léčivých přípravcích, potravinách či kosmetice v anamnéze
3. Hypersenzitivita/alergie nebo anamnéza těžkých nežádoucích reakcí na jod či jodové kontrastní látky (např. těžká porucha funkce ledvin po předchozím podání jodové kontrastní látky)
4. Hypersenzitivita/alergie na pomocné látky v hodnoceném léčebném přípravku
5. Hypersenzitivita/alergie na trimekain, příp. jiná lokální anestetika
6. Manifestní hypertyreóza nebo tyreotoxikóza
7. Plánovaný scan štítné žlázy, test funkčnosti štítné žlázy nebo léčba radiojódem

E.5 End points

E.5.1

Primary end point(s)

1. Success of the performed marking under CT control and simultaneous visualization of the marked area by the surgeon
2. Intensity, severity, and frequency (incidence) of adverse events and reactions according to established AESIs
3. Evaluation of postoperative pain using VAS (Visual Analogue Scale for Pain Assessment)
4. Occurrence of intraoperative complications (yes/no, if yes: description of complication, duration, treatment)
5. Occurrence of postoperative pulmonary and cardiovascular complications (yes/no, if yes: description of complication, duration, treatment)
6. Consumption of analgesics

1. Úspěšnost provedeného značení pod CT kontrolou a současná vizualizace značené oblasti operatérem
2. Intenzita, závažnost a frekvence (incidence) nežádoucích příhod a reakcí dle stanovených AESIs
3. Hodnocení pooperační bolestivosti pomocí VAS (Vizuální analogová škála pro hodnocení bolesti)
4. Výskyt intraoperačních komplikací (ano/ne, pokud ano: popis komplikace, trvání, léčba)
5. Výskyt pooperačních plicních a kardiovaskulárních komplikací (ano/ne, pokud ano: popis komplikace, trvání, léčba)
6. Spotřeba analgetik

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Day 1
2. Day 1, Day 2, Day 3, Day 10, Day 30
3. Day 1, Day 2, Day 3, Day 10, (Day 30)
4. Day 1
5. Day 30
6. Day 30

1. Den 1
2. Den 1, Den 2, Den 3, Den 10, Den 30
3. Den 1, Den 2, Den 3, Den 10, (Den 30)
4. Den 1
5. Den 30
6. Den 30

E.5.2

Secondary end point(s)

1. Detailed characteristic of nodules
1.1. Typification of the nodule according to Lung-RADS and subsequent correlation with the pathological finding after resection
1.2. Percentage evaluation of benign and malignant etiology of deposits
1.3. Location of the nodule in the lung parenchyma (designation of the lung segment), its size (volume in cm3), and subpleural depth of the nodule (in mm from the parietal pleura)
2. Marking method feasibility
2.1. Total radiologist's time since arrival at CT (minutes)
2.2. Total time from the end of radiologist marking to the visualization of the lesion by the surgeon (minutes)
2.3. Presence of coloring substance outside the marked area (parietal pleura, mediastinum, free thoracic cavity) - evaluated by the surgeon perioperatively (YES / NO)
2.3. Comparison of the volume of the marked area after resection with the size of the solid deposit on CT (the pathologist supplies 3 dimensions of the resection to calculate its volume (a x b x c) in cm3, the radiologist calculates the volume of the solid deposit according to the dimensions from CT)
3. Additional safety information
3.1. Evaluation of postoperative X-ray findings 2 hours after surgery, at the time of reduction of chest suction to 8 cm of the water column, 2 hours after chest drain extraction, and at the time of suture extraction during outpatient control (7th - 14th postoperative day)
3.2. Total chest drain time (days)
3.3. Length of hospitalization
3.4. Length of stay in the ICU
3.5. Postoperative quality of life according to the SF-36 questionnaire
3.6. 30-day mortality

1. Bližší charakteristika ložisek
1.1. Typizace ložiska dle Lung-RADS a následná korelace s patologickým nálezem po resekci
1.2. Procentuální zhodnocení benigní a maligní etiologie ložisek
1.3. Lokalizace ložiska v plicním parenchymu (označení plicního segmentu), jeho velikosti (objem v cm3) a subpleurální hloubky ložiska (v mm od parietální pleury)
2. Proveditelnost metody značení
2.1. Celková doba značení radiologem od příjezdu na CT (minuty)
2.2. Celková doba od ukončení značení radiologem do vizualizace ložiska operatérem (minuty)
2.3. Přítomnost barvící substance mimo označenou oblast (parietální pleura, mediastinum, volná dutina hrudní) – hodnocena operatérem peroperačně (ANO/NE)
2.4. Srovnání objemu značené oblasti po resekci s velikostí solidního ložiska na CT (patolog dodá 3 rozměry resekátu k výpočtu jeho objemu (a x b x c) v cm3, radiolog dopočítá objem solidního ložiska dle rozměrů z CT)
3. Doplňující bezpečnostní informace
3.1. Zhodnocení pooperačních RTG nálezů 2 hodiny po operaci, v době snížení hrudního sání na 8 cm vodního sloupce, 2 hodiny po extrakci hrudního drénu a v době extrakce stehů při ambulantní kontrole (7. – 14. Pooperační den)
3.2. Celková doba zavedení hrudního drénu (dny)
3.3. Délka hospitalizace
3.4. Délka pobytu na JIP
3.5. Pooperační kvalita života dle SF-36 dotazníku
3.6. 30denní mortalita

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Detailed characteristic of nodules
1.1. Day 1
1.2. Day 10
1.3. Day 1
2. Marking method feasibility
2.1. Day 1
2.2. Day 1
2.3. Day 1
3. Additional safety information
3.1. Day 1, (Day 2, Day 3, Day 10)
3.2. Day 30
3.3. Day 30
3.4. Day 30
3.5. Day 0, Day 30
3.6. Day 30

1. Bližší charakteristika ložisek
1.1. Den 1
1.2. Den 10
1.3. Den 1
2. Proveditelnost metody značení
2.1. Den 1
2.2. Den 1
2.3. Den 1
3. Doplňující bezpečnostní informace
3.1. Den 1, (Den 2, Den 3, Den 10)
3.2. Den 30
3.3. Den 30
3.4. Den 30
3.5. Den 0, Den 30
3.6. Den 30

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

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

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

resekce ložiska pomocí VTS metody bez předchozího barevného označení plicních ložisek

resection of the lesion using the VTS method without prior color marking lung lesions

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.8.5

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

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

Poslední návštěva posledního pacienta

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

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)

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

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.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

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

2021-04-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-02-20

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

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