Comparison of the effectiveness of IntraVenous FLECainide plus oral ranolazine versus intravenous flecainide alone in the cardioversion of recent onset atrial fibrillation - a randomized, prospective, multicentre, open-label study, the IV-FLEC study.

2024-514677-22-00 Therapeutic confirmatory (Phase III) Ended

Start 23 Mar 2023 · End 30 May 2025 · Status Ended · 1 EU/EEA countries · 13 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ended
Participants planned 210
Countries 1
Sites 13

Restoration of sinus rhythm in patients with recent AF onset

The aim of this study is to compare the effectiveness of combined antiarrhythmic therapy with IV flecainide and PO ranolazine versus IV flecainide monotherapy in restoring sinus rhythm in patients with recent onset (<48 hours) AF.

Key facts

Sponsor
Win Medica Pharmaceutical A.E.
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Cardiovascular Diseases [C14]
Trial duration
23 Mar 2023 → 30 May 2025
Decision date (initial)
2024-09-09
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
Win Medica Pharmaceuticals S.A.

External identifiers

EU CT number
2024-514677-22-00
EudraCT number
2021-004865-11

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Efficacy, Therapy, Safety

The aim of this study is to compare the effectiveness of combined antiarrhythmic therapy with IV flecainide and PO ranolazine versus IV flecainide monotherapy in restoring sinus rhythm in patients with recent onset (<48 hours) AF.

Conditions and MedDRA coding

Restoration of sinus rhythm in patients with recent AF onset

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

  1. 1. Patients aged ≥18 years
  2. 2. Patients with electrocardiographically confirmed AF with recent onset (self-reported onset of arrhythmia within 48 hours of starting pharmacological cardioversion).

Exclusion criteria 15

  1. 1. Coronary artery disease and/or significant structural heart disease
  2. 2. Cardiogenic shock
  3. 3. Heart failure, or decreased systolic function of the left ventricle (ejection fraction <55%)
  4. 4. Hypotension (systolic blood pressure <100mmHg)
  5. 5. Previous treatment with ranolazine within the previous 48 hours.
  6. 6. Atrioventricular conduction disorder [(2nd degree atrioventricular block, bundle branch block (RBBB + LAH or RBBB + LPH), or left bundle branch block (LBBB)}, or sick sinus syndrome in the absence of a pacemaker,
  7. 7. Hemodynamically intolerable AF
  8. 8. Creatinine clearance less than or equal to 30ml/min
  9. 9. Moderate or severe liver dysfunction
  10. 10. Prolonged QTc interval (corrected QT> 460ms)
  11. 11. Recent treatment with class Ic antiarrhythmic drugs within the previous 24 hours or with amiodarone within the previous 6 months
  12. 12. Co-administration of strong CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, voriconazole, posaconazole, HIV protease inhibitors, clarithromycin, telithromycin, nefazodone)
  13. 13. Known Brugada syndrome
  14. 14. Pregnant or breastfeeding women
  15. 15. Hypersensitivity to flecainide (flecainide acetate) or ranolazine or any of the excipients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Percentage of patients with recent onset (<48 hours) AF who were restored to sinus rhythm within 3 hours of starting treatment with IV flecainide and PO ranolazine compared with IV flecainide monotherapy.

Secondary endpoints 2

  1. Time interval from initiation of treatment with IV flecainide and PO ranolazine versus IV flecainide monotherapy to restoration of sinus rhythm in patients with recent onset (<48 hours) AF
  2. Percentage of patients with recent onset (<48 hours) AF who were restored to sinus rhythm within 6 hours of starting treatment with IV flecainide and PO ranolazine compared with IV flecainide monotherapy.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Flecardia Διάλυμα Για Ένεση/Έχχυση

PRD7419791 · Product

Active substance
Flecainide Acetate
Substance synonyms
ACETIC ACID, N-(2-PIPERIDYLMETHYL)-2,5-BIS(2,2,2-TRIFLUOROETHOXY)BENZAMIDE
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS USE
Max daily dose
2 mg/Kg milligram(s)/kilogram
Max total dose
2 mg/kg milligram(s)/kilogram
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
C01BC04 — FLECAINIDE
Marketing authorisation
62268/16/31-10-2018
MA holder
WIN MEDICA SA
MA country
Greece
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Auxiliary 1

Ranolazine

SUB10259MIG · Substance

Active substance
Ranolazine
Pharmaceutical form
PROLONGED-RELEASE TABLET
Route of administration
ORAL USE
Max daily dose
1500 mg milligram(s)
Max total dose
1500 mg milligram(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Win Medica Pharmaceutical A.E.

Sponsor organisation
Win Medica Pharmaceutical A.E.
Address
35 Attiki Odos Turnoff 33, Idipodos 1-3 Idipodos 1-3
City
Chalandri
Postcode
152 38
Country
Greece

Scientific contact point

Organisation
Win Medica Pharmaceutical A.E.
Contact name
Koufaki Giota

Public contact point

Organisation
Win Medica Pharmaceutical A.E.
Contact name
Koufaki Giota

Third parties 1

OrganisationCity, countryDuties
Next CRO SYMVOULOI FARMAKEUTIKON EPICHEIRISEON M.E.P.E.
ORG-100048347
 Maroussi, Greece On site monitoring, Code 12, Code 2, Code 5, Code 8

Locations

1 EU/EEA country · 13 investigational sites

By country

CountryMS statusPlanned subjectsSites
Greece Ended 210 13
Rest of world — 0 —

Investigational sites

Greece

13 sites · Ended
Evangelismos S.A.
Cardiology Department, Ipsiladou 45-47, 106 76, Athens
University General Hospital Of Thessaloniki Ahepa
1st Cardiology Clinic, 1st St Kiriakidis Str, 546 36, Thessaloniki
General Hospital Of Thessaloniki Papageorgiou
2nd Cardiology Clinic, Ring Road Of Thessaloniki, Ministry Of Pavlos Melas, Efkarpia
General Hospital Of Nea Ionia Konstantopouleio Patision
Cardiology Department, Konstadopoulou Th. 3-5, 142 33, Nea Ionia
Asklepieion Voulas General Hospital
Cardiology Department, Vassileos Pavlou Avenue 1, 166 73, Voula
General Hospital of Karditsa
Cardiology Clinic, Tavropou 53, 431 32, Karditsa
University General Hospital Of Alexandroupoli
University Cardiology Clinic, 6th Km Alex Polis Makris, Dragana, Alexandroupoli
General Hospital Venizeleio
Cardiology Clinic, Knossos Avenue 44, 714 09, Heraklion
Mitera S.A.
Adult Cardiology Clinic, Erythrou Stavrou Str 6, 151 23, Marousi
General University Hospital Of Larissa
University Cardiology Clinic, P. O. Box 1425, 411 10, Larissa
University General Hospital Attikon
University Clinic of Emergency Department, Rimini Street 1, 124 62, Athens
General Hospital Of Imathia Monada Veria
Cardiology Clinic, Asomata Street, 591 32, Veria
General University Hospital Of Patras
Cardiology Clinic, Rio, 265 04, Patras

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Greece 2023-03-23 2025-05-30 2023-03-23 2025-05-30

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

TitleSubmission dateStatusType
Summary of Results_EU CT 2024-514677-22-00
SUM-137019
 2026-06-02T14:52:35 Submitted Summary of Results

Layperson summary Annex V

TitleSubmission dateStatusType
Lay Person Summary of Results_EU CT 2024-514677-22-00 2026-06-02T15:00:58 Submitted Laypersons Summary of Results

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Laypersons summary of results (for publication) Lay Person Summary of Results_EU CT 2024-514677-22-00_redacted 1
Protocol (for publication) D1_Protocol_Redacted_2024-514677-22-00 1
Protocol (for publication) D1_Protocol_Redacted_2024-514677-22-00_Greek 1
Recruitment arrangements (for publication) IV-FLEC_ Blank Document for CTR transferral 1
Recruitment arrangements (for publication) K1_ Recruitment arrangements 1
Subject information and informed consent form (for publication) L1_SIS and ICF_Adults_GR_Redacted 1
Summary of Product Characteristics (SmPC) (for publication) IV-FLEC_Statement_blank_document_CTIS 1
Summary of results (for publication) Summary of Results_EU CT 2024-514677-22-00_Redacted 1
Synopsis of the protocol (for publication) D1_Protocol Synopsis_Redacted_2024-514677-22-00 1
Synopsis of the protocol (for publication) D1_Protocol Synopsis_Redacted_2024-514677-22-00_Greek 1
Synopsis of the protocol (for publication) D1_Synopsis_IV-FLEC_Layperson Protocol_v1_Synopsis Summary_EN_Redacted 1
Synopsis of the protocol (for publication) D1_Synopsis_IV-FLEC_Layperson Protocol_v1_Synopsis Summary_GR_Redacted 1

Application history

2 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-07-04 Greece Acceptable with conditions
2024-09-02
 2024-09-09
2 SUBSTANTIAL MODIFICATION SM-2 2024-10-18 Greece Acceptable
2025-02-10
 2025-02-11