Clinical Trials Register

Summary
EudraCT Number:	2018-002103-33
Sponsor's Protocol Code Number:	1080719
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:	2019-04-11
Trial results	View 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

2018-002103-33

A.3

Full title of the trial

Pulmonary vein isolation with versus without continued antiarrhythmic drug treatment in subjects with persistent atrial fibrillation: a prospective multi-centre randomized controlled clinical study (POWDER-AF2 study)

Aislamiento de la vena pulmonar con versus tratamiento antiarrítmico con medicamentos antiarrítmicos en sujetos con fibrilación auricular persistente: un estudio clínico prospectivo aleatorizado, multicéntrico y prospectivo (estudio POWDER-AF2)

A.3.1

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

Continuing versus stopping heart rhythm medication after an operation restoring your normal heart rhythm in patients with a heart rhythm disorder: a study across multiple hospitals.

Continuar versus detener la medicación para el ritmo cardíaco después de una operación que restaura su ritmo cardíaco normal en pacientes con un trastorno del ritmo cardíaco: un estudio en varios hospitales.

A.3.2

Name or abbreviated title of the trial where available

POWDER-AF2

A.4.1

Sponsor's protocol code number

1080719

A.5.4

Other Identifiers

Name:

ClinicalTrials.gov

Number:

NCT03437356

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	AZ Sint-Jan Brugge-Oostende AV
B.1.3.4	Country	Belgium
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	BIOSENSE WEBSTER, INC.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Anthony Demolder
B.5.2	Functional name of contact point	Anthony Demolder
B.5.3	Address:
B.5.3.1	Street Address	Ruddershove 10
B.5.3.2	Town/ city	Bruges
B.5.3.3	Post code	8000
B.5.3.4	Country	Belgium
B.5.6	E-mail	anthony.demolder@ugent.be

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	Apocard
D.2.1.1.2	Name of the Marketing Authorisation holder	MEDA PHARMA S.L. C/ General Aranaz, 86 28027 Madrid España
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.3.1	Product name	Apocard
D.3.2	Product code	Not applicable
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	Flecainidacetat
D.3.9.1	CAS number	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 milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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	Rytmonorm
D.2.1.1.2	Name of the Marketing Authorisation holder	Teva B.V. Swensweg 5 2031GA Haarlem Paises Bajos
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.3.1	Product name	Rytmonorm
D.3.2	Product code	Not applicable
D.3.4	Pharmaceutical form	Film-coated 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	PROPAFENONE HYDROCHLORIDE
D.3.9.1	CAS number	34183-22-7
D.3.9.4	EV Substance Code	SUB04077MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	300
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: 3
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	Sotalol
D.2.1.1.2	Name of the Marketing Authorisation holder	TEVA PHARMA S.L.U. C/ Anabel Segura, 11, Edificio Albatros B, 1ª planta 28108 Alcobendas (Madrid), E
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.3.1	Product name	Sotalol
D.3.2	Product code	Not applicable
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	SOTALOL HYDROCHLORIDE
D.3.9.1	CAS number	959-24-0
D.3.9.4	EV Substance Code	SUB04512MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	160
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

Symptomatic persistent atrial fibrillation: atrial fibrillation, that lasts longer than 7 days, including episodes that are terminated by cardioversion, either with drugs or by direct current cardioversion, after 7 days or more. Episodes of atrial fibrillation have to be accompanied by symptoms.

Fibrilación auricular persistente sintomática: fibrilación auricular, que dura más de 7 días, incluidos los episodios que terminan por cardioversión, ya sea con medicamentos o por cardioversión actual, después de 7 días o más. Los episodios de fibrilación auricular deben ir acompañados de síntomas.

E.1.1.1

Medical condition in easily understood language

Atrial fibrillation is a heart rhythm disorder: an irregular and often rapid heart rate.

La fibrilación auricular es un trastorno del ritmo cardíaco: una frecuencia cardíaca irregular ya menudo rápida.

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	LLT
E.1.2	Classification code	10071667
E.1.2	Term	Persistent atrial fibrillation
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

We aimed to study whether continued ADT (antiarrhythmic drug treatment) (ADT ON) beyond the 3 month blanking period reduces recurrrence of atrial tachyarrhyhtmia (ATA) in the first year after contact-force guided pulmonary vein isolation (PVI) for persistent AF.

El objetivo fue estudiar si el tratamiento con ADT (tratamiento antiarrítmico con medicamentos antirrítmicos) (ADT ON) más allá del período de cegamiento de 3 meses reduce la recurrencia de taquiarritmia auricular (ATA) en el primer año después del aislamiento de la vena pulmonar guiada por contacto con fuerza (FA) para la FA persistente.

E.2.2

Secondary objectives of the trial

Secondary Endpoints:
Time to persistent AF
Atrial tachyarrhythmia recurrence in patients with early peristent AF (defined as AF ≤3 months)
Incidence of repeat ablation
Unscheduled visits and hospitalisation
Antiarrhtyhmic drug or ablation related adverse events
Quality of life and symptoms
Outcome after repeat ablation

Puntos finales secundarios:
Tiempo para la FA persistente
Recurrencia de taquiarritmia auricular en pacientes con FA peristente temprana (definida como FA ≤3 meses)
Incidencia de ablación repetida
Visitas no programadas y hospitalización.
Medicamentos antiarrítmicos o eventos adversos relacionados con la ablación.
Calidad de vida y síntomas.
Resultado después de la repetición de la ablación

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patient with symptomatic persistent AF, resistant to ongoing or prior ADT (failed ADT)
Patients is considered to have persistent AF if the patient has suffered any prior AF episode ≥7 days (ESC 2016 guidelines).
2. Before PVI, there was at least one episode of persistent AF in the last year.
3. Signed Patient Informed Consent Form.
4. Age 18 years or older.
5. Able and willing to comply with all follow-up testing and requirements.

1. Paciente con FA sintomática persistente, resistente a ADT en curso o anterior (ADT fallido)
Se considera que los pacientes tienen FA persistente si el paciente ha sufrido algún episodio de FA anterior ≥7 días (pautas de ESC 2016).
2. Antes de PVI, hubo al menos un episodio de FA persistente en el último año.
3. Formulario de consentimiento informado firmado por el paciente.
4. Edad 18 años o más.
5. Capaz y dispuesto a cumplir con todas las pruebas y requisitos de seguimiento.

E.4

Principal exclusion criteria

1. Patients not willing or not suited to take any class IC or III ADT.
2. Any prior AF episode ≥12 months, or any recurrence of AF <3 days after cardioversion.
3. Presence of structural heart disease on echo criteria:
severe valvular heart disease
LA volume >37mL/m2 and/or LA size >50mm
LV ejection fraction <35% (except if suspected tachycardiomyopathy)
septal diameter >15mm
4. BMI >35
5. Recent (<3 months) CABG, myocardial infarction, CVA, uncontrolled heart failure or angina
6. Active illness or systemic infection or sepsis
7. AF secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause
8. Awaiting cardiac transplantation or other cardiac surgery
9. Documented left atrial thrombus or atrial myxoma on imaging
10. History of blood clotting or bleeding abnormalities
11. Enrollment in any other study evaluating another device or drug
12. Women with childbearing potential
13. Life expectancy less than 12 months
14. Contraindication for catheter ablation (intramural thrombus, tumor or other abnormality that precludes catheter introduction, contraindication to anticoagulation therapy)

1. Pacientes que no están dispuestos o no son adecuados para tomar cualquier clase IC o III ADT.
2. Cualquier episodio de FA anterior ≥12 meses, o cualquier recurrencia de FA <3 días después de la cardioversión.
3. Presencia de cardiopatía estructural en criterios de eco:
cardiopatía valvular grave
Volumen LA> 37 ml / m2 y / o tamaño LA> 50 mm
Fracción de eyección del VI <35% (excepto si se sospecha taquicardiomiopatía)
diámetro septal> 15 mm
4. IMC> 35
5. Reciente (<3 meses) CABG, infarto de miocardio, ACV, insuficiencia cardíaca no controlada o angina
6. Enfermedad activa o infección sistémica o sepsis.
7. FA secundaria a desequilibrio electrolítico, enfermedad tiroidea o causa reversible o no cardíaca
8. En espera de trasplante cardíaco u otra cirugía cardíaca
9. Trombo auricular izquierdo o mixoma auricular documentado en imágenes
10. Antecedentes de coagulación sanguínea o anormalidades en el sangrado.
11. Inscripción en cualquier otro estudio que evalúe otro dispositivo o medicamento
12. Mujeres con potencial de maternidad.
13. Esperanza de vida inferior a 12 meses.
14. Contraindicación para la ablación con catéter (trombo intramural, tumor u otra anomalía que impide la introducción del catéter, contraindicación para el tratamiento con anticoagulantes)

E.5 End points

E.5.1

Primary end point(s)

Primary Endpoint:
Any documented ATA (atrial fibrillation, AF, atrial tachycardia, AT, atrial flutter, AFL) lasting >30s from 3 months through 12 month follow-up after the first procedure

Variable principal:
Cualquier ATA documentada (fibrilación auricular, FA, taquicardia auricular, AT, aleteo auricular, AFL) que dura> 30 s desde 3 meses hasta 12 meses de seguimiento después del primer procedimiento

E.5.1.1

Timepoint(s) of evaluation of this end point

- Enrollment
- (T0) PVI
- (T1) 1 month
- (T3) 3 months +/- 30 days
- (T6) 6 months +/- 30 days
- (T12) 12 months +/- 30 days

- inscripción
- (T0) PVI
- (T1) 1 mes
- (T3) 3 meses +/- 30 días
- (T6) 6 meses +/- 30 días
- (T12) 12 meses +/- 30 días

E.5.2

Secondary end point(s)

Secondary Endpoints:
Time to persistent AF
ATA recurrence in patients with early peristent AF (defined as AF ≤3 months)
Incidence of repeat ablation
Unscheduled visits and hospitalisation
ADT or ablation related adverse events
QOL and symptoms
Outcome after repeat ablation

Puntos finales secundarios:
Tiempo para la FA persistente
Recurrencia de ATA en pacientes con FA peristente temprana (definida como FA ≤3 meses)
Incidencia de ablación repetida
Visitas no programadas y hospitalización.
ADT o eventos adversos relacionados con la ablación.
CV y síntomas
Resultado después de la repetición de la ablación

E.5.2.1

Timepoint(s) of evaluation of this end point

- Enrollment
- (T0) PVI
- (T1) 1 month
- (T3) 3 months +/- 30 days
- (T6) 6 months +/- 30 days
- (T12) 12 months +/- 30 days

- inscripción
- (T0) PVI
- (T1) 1 mes
- (T3) 3 meses +/- 30 días
- (T6) 6 meses +/- 30 días
- (T12) 12 meses +/- 30 días

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

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

Yes

E.8.1.7.1

Other trial design description

Estudio prospectivo internacional multicéntrico, aleatorizado (1: 1), de etiqueta abierta, punto fin

Prospective international multi-center, randomized (1:1), open label, blinded endpoint study

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

Sin medicación después de 3 meses post ablación.

No medication after 3 months post-ablation

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

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

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 (Last visit of the last patient)

LVLS (última visita del último paciente)

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

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.1.3.1

Number of subjects for this age range:

160

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

220

F.4.2.2

In the whole clinical trial

220

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)

Not different from expected normal treatment.

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

2019-04-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-03-08

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

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IMP with orphan designation in the indication
Orphan Designation Number:
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