E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
F373280 is a new therapy based on DHA delivery (pro-drug) developed for the maintenance of sinus rhythm after electrical cardioversion in persistent atrial fibrillation (AF) patients with chronic heart failure.
The results of a pharmacological study performed in animals evidenced that DHA reduces the duration of Atrial Fibrillation (AF) induced by burst pacing. |
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E.1.1.1 | Medical condition in easily understood language |
F373280 is a new therapy based on DHA delivery developed for the maintenance of sinus rhythm after electrical cardioversion in persistent atrial fibrillation patients with chronic heart failure.
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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 | PT |
E.1.2 | Classification code | 10003658 |
E.1.2 | Term | Atrial fibrillation |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary:
Efficacy of F373280 on the maintenance of sinus rhythm after direct electrical cardioversion in patients with persistent atrial fibrillation and chronic heart failure
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E.2.2 | Secondary objectives of the trial |
Secondary:
- Efficacy of F373280 on the efficiency of direct electrical cardioversion
- Effect of F373280 on echocardiographic parameters
- Safety and tolerability of F373280 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Demographic Characteristics and Other Baseline Characteristics:
1.Men or women aged more than 18 years (inclusive)
2.Patients with current episode of persistent AF between 7 days and 6
months duration for whom electrical cardioversion is warranted
3.Previous history of first documented episode of persistent AF.
4.Previous history of ischemic or non ischemic heart failure
5.NYHA class I or II chronic heart failure at selection and at inclusion
6.Left ventricular systolic dysfunction defined at selection and at
inclusion by a reduced left ventricular ejection fraction (LVEF) ≥ 30%
and ≤ 45% or for patients with a LVEF > 45%:
•an increased left ventricular end-diastolic size (diameter ≥ 60 mm
and/or > 32 mm/m² and/or volume > 97 ml/m²)
•and/or an increased left ventricular end-systolic size
(diameter > 45 mm and/or > 25 mm/m² and/or volume > 43 ml/m²)
•and/or a reduced left ventricular outflow tract velocity time integral <
15 cm
7.On appropriate, stable medical treatments for heart failure, including a
diuretic and/or angiotensin-converting enzyme, and/or angiotensin-
receptor blocker and/or mineralocorticoid receptor (MR) antagonists,
and/or betablockers
8.Left atrial area ≤ 40 cm² at selection and at inclusion
9.Patients treated or having to be treated by vitamin K antagonist
10.For female patient of child-bearing potential:
•In all the countries except Italy:
-Use of an effective method of contraception (hormonal contraception or
intra-uterine device) assessed by the investigator, for at least 2 months
before the selection in the study, and agreement to go on using it during
the whole duration of the study and up to 1 month after the last dose of
the study treatment
-Documented as surgically sterilized
•In Italy only:
-Absolute abstention from sexual intercourse during the whole duration
of the study and for a month after the end of the study or
-Use of double barrier contraception method (use of effective medical
contraception method) from at least 2 months before the start of the
study to the entire duration of the study and for a month after the end of
the study or
-Documented as surgically sterilized
11.For female patient of child-bearing potential: negative urine
pregnancy test at inclusion
12.For male with a child-bearing potential partner (In Italy only):
-Absolute abstention from sexual intercourse during the whole duration
of the study and for 3 months after the end of the study or
-Use of double barrier contraception method (use of condom for male
and effective contraception method for the partner) from the entire
duration of the study to 3 months after the end of the study.
Ethical / legal considerations:
13.Having signed his/her written informed consent,
14.Affiliated to a social security system, or is beneficiary (if applicable in
the national regulation)
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E.4 | Principal exclusion criteria |
Non-Inclusion Criteria:
Criteria related to pathologies:
1.No previous history of first documented episode of persistent AF
2.More than two successful cardioversions (electrical or
pharmacological) in the last 6 months
3.Secondary Atrial Fibrillation due to alcohol or severe valvular heart
disease (grade III to IV)
4.NYHA class III or IV heart failure at selection or at inclusion
5.Thyroid disease uncontrolled by treatment: TSH ± T4L ± T3L to be
checked in case of treatment for thyroid disease
6.Myocardial infarction or unstable angina or presence of unstable
ischemic coronaropathy assessed by coronarography or cardiac stress
test (Echo stress, exercise stress test, nuclear or MR perfusion
evaluation methods) within 6 months before selection
7.Severe chronic kidney disease (creatinine ≥ 25 mg/L or estimated
glomerular filtration rate < 30 ml/min) at selection
8.Bradycardia (HR ≤ 50 bpm)
9.Hyperkalemia or hypokalemia (according to the standards of local
laboratories) at selection
10.Cardiac surgery within 3 months before selection or planned during
the study duration
Criteria related to treatments:
11.Previously ineffective pharmacological or electrical cardioversion
12.Concomitant treatment with ranolazine or any antiarrhythmic drug
(within 7 days prior to selection), except amiodarone, dronedarone and
stable dose of digoxin, betablockers, calcium-blockers
13.Concomitant treatment with oral amiodarone or dronedarone from
selection
14.Concomitant treatment with intravenous amiodarone from selection
15.Patient requiring a cardiac resynchronization therapy (CRT) or having
undergone CRT implantation within the last 6 months
16.Treatment with any Polyunsaturated Fatty Acid (PUFA) within the last
3 months
17.Dietary supplement with ω 3 or ω 6 according to investigator's
judgement
18.Having undergone any form of ablation therapy for AF
19.Patient treated with oral anticoagulant treatment other than vitamin
K antagonist: new oral anticoagulants (dabigatran, rivaroxaban,
apixaban), or treated with irreversible antiplatelet agents P2Y12
inhibitors such as ticlopidine, clopidogrel or prasugrel
Other criteria:
20.Patient liable not to comply with protocol instructions and/or with
treatment, in the investigator's opinion
21.Patient having taken part in a clinical trial in the preceding 2 months
or taking part in a trial at the time of selection
22.Patient linguistically or mentally unable to understand the nature,
objectives and possible consequences of the trial, or refusing to patient
himself/herself to its constraints
23.Patient family member or work associate (secretary, nurse,
technician,..) of the Investigator
24.Patient having forfeited his / her freedom by administrative or legal
award or being under guardianship
25. Breastfeeding female patient |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time to first Atrial Fibrillation recurrence or atrial flutter emergence
defined by the time to first episode of AF or atrial flutter lasting for at
least 10 minutes. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Adverse events
Vital signs
Physical examination
Standard 12-lead ECG
Haematology
Biochemistry
Coagulation parameters |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |