Clinical Trials Register

Summary
EudraCT Number:	2013-000048-24
Sponsor's Protocol Code Number:	SE-CVC02/2013
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2013-04-03
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2013-000048-24

A.3

Full title of the trial

Randomised clinical trial evaluating the safety and effectiveness of esmolol and metoprolol for heart rate control of patients referred to coronary CT angiography

Randomizált klinikai vizsgálat, mely az esmolol és metoprolol hatásosságát és biztonságosságát hasonlítja össze coronaria CT angiographia vizsgálatra kerülő betegek szívfrekvencia kontrolljára

A.3.1

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

Evaluation of the safety and effectiveness of esmolol and metoprolol for heart rate reduction during heart CT examination

Esmolol és metoprolol hatékonyságának és biztonságosságának vizsgálata pulzus csökkentésre szív CT vizsgálat során

A.4.1

Sponsor's protocol code number

SE-CVC02/2013

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	Hear Center of Semmelweis University
B.1.3.4	Country	Hungary
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	Heart Center of Semmelweis University
B.4.2	Country	Hungary
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Heart Center of Semmelweis University
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	Varosmajor 68.
B.5.3.2	Town/ city	Budapest
B.5.3.3	Post code	1122
B.5.3.4	Country	Hungary
B.5.4	Telephone number	36206663263
B.5.6	E-mail	karolyimisi@gmail.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	Esmocard 2500 mg / 10ml concentrate for solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Orpha-Devel Handels und Vertriebs GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Hungary
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	Esmocard
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous bolus use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Esmocard
D.3.9.1	CAS number	84057-94-3
D.3.9.3	Other descriptive name	ESMOLOL
D.3.9.4	EV Substance Code	SUB13718MIG
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	250
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	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	Betaloc 1 mg / ml solution for infusion
D.2.1.2	Country which granted the Marketing Authorisation	Hungary
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	Betaloc
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous bolus use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Betaloc solution for infusion
D.3.9.3	Other descriptive name	METOPROLOL TARTRATE
D.3.9.4	EV Substance Code	SUB03275MIG
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	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	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.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

Heart rate control of patients referred to coronary computed tomography angiography (CCTA) due to suspected coronary artery disease are to investigated with esmolol and metoprolol. Acquiring diagnostic image quality with CCTA requires relative low and stable heart rate of the patients during examination. Thus, heart rate control with beta-blocker medication (esmolol, metoprolol) is recommended. However no current guideline is available regarding esmolol administration during CCTA.

Koszorúérbetegség miatt coronaria computer tomographias angiographia (CCTA) vizsgálatra kerülő betegek vizsgálat alatti szívfrekvencia kontrolljának lehetőségét vizsgáljuk esmolol és metoprolol alkalmazásával. CCTA során diagnosztikus képminőség biztosításához a betegek relatív alacsony és stabil szívritmusa szükséges. Ennek megfelelően szívfrekvencia kontroll ajánlott béta-blokkoló gyógyszer alkalmazásával. Ugyanakkor nincsen kidolgozott irányelv esmolol alkalmazására CCTA vizsgálat során.

E.1.1.1

Medical condition in easily understood language

Heart rate control during heart CT examination by patients with suspected coronary artery disease, as acquiring diagnostic images needs low and stable heart rate.

Pulzuskontroll szív CT vizsgálat során betegeknél koszorúérbetegség gyanúja miatt. Diagnosztikus felvételek készítése stabil és alacsony szívritmust igényel.

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10011078
E.1.2	Term	Coronary artery disease
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

Our aim is to test the capability, satefy and effectiveness of ultra-short acting beta-blocker esmolol for heart rate control of patients undergo coronary CT angiography as compared to commonly used metoprolol.
This is a randomised single center phase III clinical trial. Patients undergo examination will be stratified according to gender and than randomised to the esmolol and metoprolol group.

A vizsgálat célja az ultra-rövid hatású béta-blokkoló esmolol alternatív, intravénás bólusban való adagolás alkalmazhatósgának, hatékonyságának és biztonságosságának vizsgálata coronary CT angiographias vizsgálatra kerülő betegek frekvenciakontrolljára a gyakorlatban használatos metoprolollal összehasonlításban.
A vizsgálat randomizált egycentrumú fázis III klinikai vizsgálat. A vizsgálatra kerülő betegeket nem szerint stratifikáljuk, majd randomizáljuk az esmolol és metoprolol vizsgálati csoportba. Az elsődleges vizsgálati végpont 65/perc alatti szívfrekcencia elérése a coronaria CT vizsgálat során.

E.2.2

Secondary objectives of the trial

Not applicable

Nem vonatkozik

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Age between 18-90 years
- Clinical indication of coronary computed tomography angiography
- Understood of patient information form and given written consent

- 18-90 év közötti életkor
- Coronaria computer tomographia angiographia vizsgálat klinikai indikációja
- Betegtájékoztató megértése, valamint a beleegyező nyilatkozat elfogadása, aláírása

E.4

Principal exclusion criteria

- Any clinical contraindication of coronary computed tomography angiography
- Any clinical contraindication of beta-blocker drug administration
- Atrial fibrillation, atrial flutter within three months prior to examination or frequent irregular, high heart rate
- implanted pacemaker or implanted cardioverter defibrillator
- acute heart faiure, or known non-ischemic cardiomyopathy
- pregnancy

- A coronaria CT angiographia bármely klinikai kontraindikációja
- Béta-blokkoló gyógyszer alkalmazásának bármely klinikai kontraindikációja
- A vizsgálatot megelőző három hónapban jelentkező pitvarfibrilláció, pitvari fluttern, gyakori irreguláris vagy gyors szívritmus
- Pacemakerrel vagy implantálható cardioverter defibrillátorral élő beteg
- Akut szívelégtelenség, vagy ismert nem ischaemias cardiomyopathia
- Terhesség

E.5 End points

E.5.1

Primary end point(s)

The firs endpont is the proportion of patients who reach 65 bpm or slower heart rates in each group during the examination (esmolol vs. metoprolol group).

Az első végpont a betegek hányada akik elérik a 65 per perc vagy alacsonyabb szívfrekvenciát a vizsgálat alatt mindkét csoportban (esmolol vs. metoprolol csoport).

E.5.1.1

Timepoint(s) of evaluation of this end point

At the time of acquisition of contrast enhanced scan (TS) during the coronaray computed tomography angiography examination.

A kontrasztanyagos felvételek elkészítésének időpontja (TS) a coronaria computer tompgraphia angiographia vizsgálat során.

E.5.2

Secondary end point(s)

1) The proportion of patients experienced bradycardia (HR<50 bpm), and/or hypotension (systolic blood pressure <100 mmHg) after study drug administration.
2) The proportion of female patients who achieve the target heart rate of HR≤65 bpm.
3) The effective radiation dose in the esmolol versus the metoprolol group.

1) Azon betegek hányada, akiknél bradycardia (HR<50 bpm), vagy hypotensio (szisztolés vérnyomás<100 mmHg) lép fel a vizsgálati szer adását követően.
2) Azon nőbetegek hányada, melyek elérik a cél ≤65 per perc szívfrekvenciát.
3) Az effektív vizsgálati sugárdózis különbsége az esmolol és metroprolol vizsgálati csoportok között.

E.5.2.1

Timepoint(s) of evaluation of this end point

1) Immediately after the coronary computed tomography angiography examination (T2) and 30 minutes after the examination (T3)
2) At the time of contrast enhanced scan (TS) during the computer tomography angiography examination
3) After the performance of the coronary computed tomography angiography examination

1) Közvetlenül a coronaria computer tomographias vizsgálat után (T2) és 30 perc elteltével a vizsgálatot követően (T3)
2) A kontrasztos felvételek készítésekor (TS) a computer tomographia angiographia vizsgálat során
3) A coronaria computer tomographia vizsgálat befejeztével

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

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

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

Yes

E.8.1.4

Double blind

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

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.8.5

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

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:

400

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

500

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

2013-03-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-03-19

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

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