Clinical Trials Register

Summary
EudraCT Number:	2014-003641-95
Sponsor's Protocol Code Number:	SELECTI-CARFAP
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2014-11-11
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

Spain - AEMPS

A.2

EudraCT number

2014-003641-95

A.3

Full title of the trial

Randomized clinical trial to study effective pharmacological cardioversion of paroxysmal atrial fibrillation by blocking ionic currents atrioselectivas by treatment with vernakalant vs Flecainide

Ensayo clínico aleatorizado para estudio de cardioversión farmacológica efectiva de fibrilación auricular paroxística mediante bloqueo de las corrientes iónicas atrioselectivas por tratamiento con Vernakalant vs Flecainida

A.3.1

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

study of effective pharmacological cardioversion of paroxysmal atrial fibrillation with flecainide vs vernakalant

estudio de cardioversión farmacológica efectiva de fibrilación auricular paroxística con Vernakalant vs Flecainida

A.3.2

Name or abbreviated title of the trial where available

SELECTI-CARFAP

A.4.1

Sponsor's protocol code number

SELECTI-CARFAP

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	Nicasio Pérez Castellano
B.1.3.4	Country	Spain
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	FUNDACIÓN PARA LA INVESTIGACIÓN BIOMEDICA HOSPITAL CLÍNICO SAN CARLOS
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	HOSPITAL CLINICO SAN CARLOS
B.5.2	Functional name of contact point	SERVICIO DE CARDIOLOGÍA
B.5.3	Address:
B.5.3.1	Street Address	PROFESOR MARTIN LAGOS S/N
B.5.3.2	Town/ city	MADRID
B.5.3.3	Post code	28040
B.5.3.4	Country	Spain
B.5.4	Telephone number	349133030007510
B.5.5	Fax number	349133035273527

D. IMP Identification
D.IMP: 1
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	Flecainida
D.2.1.1.2	Name of the Marketing Authorisation holder	MEDA Pharma SAU
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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.3.4	Pharmaceutical form
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	54143-56-5
D.3.9.1	CAS number	54143-56-5
D.3.9.2	Current sponsor code	54143-56-5
D.3.9.3	Other descriptive name	FLECAINIDE ACETATE
D.3.9.4	EV Substance Code	SUB13894MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
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	vernakalant
D.2.1.1.2	Name of the Marketing Authorisation holder	Cardiome UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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.3.4	Pharmaceutical form
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SUB30707
D.3.9.1	CAS number	SUB30707
D.3.9.2	Current sponsor code	SUB30707
D.3.9.3	Other descriptive name	VERNAKALANT HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB30707
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3
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

Atrial fibrillation paroxysmal

fibrilación auriclar paroxistica

E.1.1.1

Medical condition in easily understood language

atrial fibrillation

fibrilación auriclar

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	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10003661
E.1.2	Term	Atrial fibrillation paroxysmal
E.1.2	System Organ Class	100000004849

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Effect of vernakalant and flecainide on the atrial activation and its relationship to effective cardioversion.

Efecto del Vernakalant y la Flecainida sobre la frecuencia de activación auricular y su relación con la cardioversión eficaz.

E.2.2

Secondary objectives of the trial

Evolution of the spectral parameters and rate of cardioversion in patients with less or more than 24 h after the beginning of the episode of paroxysmal AF.
Identification of new spectral and clinical predictors to estimate the probability of success of the drugs studied
Computational simulation using mathematical models of response in atrial fibrillation
Evaluate the clinical symptoms and patient perception during cardioversion strategy

Evolución de los parámetros espectrales y tasa de cardioversión de los pacientes con menos o más de 24 h de evolución desde el inicio del episodio de FA paroxística.
Identificación de nuevos predictores espectrales y clínicos que permitan estimar las probabilidades de éxito de los fármacos a estudio
Simulación mediante modelos computacionales matemáticos, de la respuesta a la terminación de fuentes reentrantes y FA con los fármacos utilizados a nivel clínico
Evaluar la sintomatología y percepción clínica del paciente durante la estrategia de cardioversión

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1 Patients with paroxysmal atrial fibrillation with less of 48 hours of evolution.
2 Hemodynamically stable patients (systolic blood pressure> 100 mm Hg and <160 mm Hg. Diastolic blood pressure <95 mm Hg).
3 Weight from 45 to 136 kg.
4. Adequate anticoagulant therapy according to clinical practice guidelines of European Society of Cardiology in atrial fibrillation paroxysmal duration less of 48 hours.
5 Aging between 20 and 65 years old.
6 Patients must agree and be able to grant informed consent.

1. Pacientes con fibrilación auricular paroxística de <48 horas de evolución
2. Pacientes estables hemodinámicamente (presión arterial sistólica> 100 mm Hg y <160 mm Hg. Presión arterial diastólica <95 mm Hg).
3. Peso de 45 a 136 kg.
4. Terapia anticoagulante adecuada según las guías de práctica clínica de Sociedad Europea de Cardiología en FA paroxística de duración < 48 horas.
5. Los pacientes deben tener entre 20 y 65 años de edad.
6. Los pacientes deben estar de acuerdo y ser capaces de otorgar el consentimiento informado.

E.4

Principal exclusion criteria

1 QT interval> 440 milliseconds, long QT familiar syndrome or previous history of Torsades de Pointes syndrome.
2 Symptomatic bradycardia or ventricular rate <50 bpm without a pacemaker, or QRS interval> 140 milliseconds.
3 Patients with Class IV heart failure according to the New York Heart Association or congestive heart failure requiring intravenous inotropic therapy.
4. cardiogenic or septic shock, chronic myocardial infarction, acute coronary syndrome, or heart surgery in <30 days before recruitment.
5 valve stenosis, obstructive hypertrophic cardiomyopathy, restrictive cardiomyopathy, or constrictive pericarditis.
6. previous electrical cardioversion ineffective.
7 Having received an investigational drug within 60 days before inclusion or received vernakalant previously.
8 Secondary causes of atrial fibrillation, uncorrected electrolyte imbalance, or digoxin toxicity.
9 intravenous / oral treatment with class I or III antiarrhythmic drugs (except amiodarone) in the previous 48 hours.
10 intravenous / oral amiodarone within 3 months prior.
11 pregnant or nursing women.
12. intolerance or allergy to any of the two study drugs.
13 Patients who do not give their informed consent.

1. Intervalo QT corregido> 440 milisegundos, síndrome de QT largo familiar o historia previa de Torsades de Pointes.
2. Bradicardia sintomática o frecuencia ventricular <50 lpm sin un marcapasos, o intervalo QRS> 140 milisegundos.
3. Pacientes con insuficiencia cardíaca Clase IV según la New York Heart Association o insuficiencia cardíaca congestiva que requiere tratamiento inotrópico intravenoso.
4. Shock cardiogénico o séptico, infarto de miocardio crónico, síndrome coronario agudo, o cirugía cardíaca en los <30 días antes de la inclusión.
5. Estenosis valvular, miocardiopatía hipertrófica obstructiva, miocardiopatía restrictiva, o pericarditis constrictiva.
6. Cardioversión eléctrica previa ineficaz.
7. Haber recibido un fármaco en investigación dentro de los 60 días antes de la inclusión o haber recibido Vernakalant con anterioridad.
8. Causas secundarias de FA, desequilibrio electrolítico no corregido, o toxicidad por digoxina .
9. Tratamiento intravenoso/oral con antiarrítmicos clase I o III (excepto amiodarona) en las 48 horas previas.
10. Amiodarona intravenosa/oral dentro de los 3 meses previos.
11. Mujeres embarazadas o en lactancia.
12. Intolerancia o alergia a cualquiera de los dos fármacos en estudio.
13. Pacientes que no otorguen su consentimiento informado

E.5 End points

E.5.1

Primary end point(s)

yes no question cardioversion to sinus rhythm

cardioversion a ritmo sinusal si/no

E.5.1.1

Timepoint(s) of evaluation of this end point

5,10,15,20,25,30,40,50,60,70,80 and 90 minutes after drug administration

5,10,15,20,25,30,40,50,60,70,80 y 90 minutos despues de la administración

E.5.2

Secondary end point(s)

Demographic data: age, weight, height, BMI, gender and personal history, cardiovascular risk factors, pulmonary diseases, chronic renal failure and others.
Related to drug safety: Respiratory complications, hemodynamic complications and other side effects.
Related to the perception of the patient: quality of life questionnaire (AF-QoL).

Datos demográficos: edad, peso, altura, IMC, sexo y los antecedentes personales, factores de riesgo cardiovascular, alteraciones pulmonares, insuficiencia renal crónica y otros.
Relacionadas con la seguridad: complicaciones respiratorias, complicaciones hemodinámicas and otras efectos secundarios.
Relacionados con la percepción del paciente: cuestionario de calidad de vida (AF-QoL).

E.5.2.1

Timepoint(s) of evaluation of this end point

Demographic data: at the begining.
Related to drug safety: 5,10,15,20,25,30,40,50,60,70,80 and 90 minutes after drug administration.
Related to the perception of the patient: at the of the participation.

Datos demograficos: al inicio del estudio
Relacionadas con la seguridad: 5,10,15,20,25,30,40,50,60,70,80 y 90 minutos despues de la administración
Relacionados con la percepción del paciente: al final del estudio.

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

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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

uvup

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)

Information regarding adverse events will be collected from the time the patient receives the first dose of study medication until the end of the study follow unless additional monitoring is justified by the researcher.
It is necessary for any serious adverse event that occurs after 30 days of administration of study medication if the investigator believes may be related to the same register.

Información concerniente a acontecimientos adversos desde el momento en que el paciente recibe la primera dosis de la medicación del estudio hasta que se finalice el seguimiento del estudio a no ser que esté justificado un seguimiento adicional por parte del investigador.
Es necesario que se registre cualquier acontecimiento adverso grave que ocurra transcurridos 30 días de la administración de la medicación del estudio si el investigador considera que puede estar relacionado con la misma.

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

2015-02-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-02-04

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

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