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Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion (RAFFAELLO)

Primary Purpose

Persistent Atrial Fibrillation

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ranolazine
Ranolazine
Ranolazine
Placebo
Sponsored by
Menarini Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Persistent Atrial Fibrillation focused on measuring Atrial Fibrillation, Ranolazine, Arrhythmias, Cardiac, Antiarrhythmic Agents, Cardiac Electroversion, Ranexa

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female patients 18 years and older
  • Patients with persistent AF suitable for electrical direct current cardioversion (DCC)
  • A female of childbearing potential may be enrolled providing she has a negative pregnancy test at baseline and is routinely using an effective method of birth control resulting in a low failure rate until end of study
  • Able to give written informed consent before any study related procedure
  • Able to attend all the visits scheduled in the study

Exclusion Criteria:

  • Patients with first diagnosed AF or patients with paroxysmal AF
  • Patients with long-standing persistent AF or permanent AF
  • Patients having known concurrent temporary secondary causes of AF such as alcohol intoxication, pulmonary embolism, hyperthyroidism, pneumonia, hypoxemia, acute pericarditis or myocarditis
  • Patients having undergone atrial catheter ablation for AF
  • Patients carrying a pacemaker
  • Patients with electrolytes imbalances that may cause cardiac arrhythmias, e.g. potassium < 3.5 mmol/L or > 5.5 mmol/L
  • Patients with any contra-indications to Ranexa according to the drug-specific product characteristics
  • Patients taking class I or Class III antiarrhythmic agents within 3 days of planned randomisation
  • Patients taking beta-blockers unless used on stable doses for at least 2 weeks prior to the planned randomisation. Single doses of Intravenous beta-blockers are allowed up to 10 hours from the planned randomisation
  • Patients taking Dronedarone or oral Amiodarone within 2 weeks and 3 months of planned randomisation, respectively
  • Patients with a history of ECG abnormalities that in the opinion of the Investigator render the subject unsuitable for the trial, including history of congenital or a family history of long QT syndrome and a QTc interval ≥500 msec at Screening
  • Patients with congestive heart failure NYHA grade III and IV;
  • Patients with any serious intercurrent illness (including psychiatric and neurological disorders) which, in the opinion of the Investigator, is incompatible with the protocol.
  • Patients taking Metformin at a total daily dose greater than 1000 mg.
  • Patients taking Simvastatin at a total daily dose greater than 20 mg.

Sites / Locations

  • Universitätsmedizin Göttingen (UMG), Kardiologie und Pneumologie
  • FONDAZIONE IRCCS, Dip. Cardiotoracovascolare (U.C.C.)
  • Hospital Clínic i Provincial de Barcelona, Servicio de Cardiología-Sección de Arritmias
  • St. George's University of London

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Ranolazine low dose

Ranolazine intermediate dose

Ranolazin high dose

Placebo

Arm Description

Ranolazine, low dose, oral, BID

Ranolazine, intermediate dose, oral, BID

Ranolazine, high dose, oral, BID

Placebo (sugar pill), oral, BID.

Outcomes

Primary Outcome Measures

Time From Randomization to First Documented AF Recurrence.
Time to first AF recurrence reported by patient-reported TT-ECG or 12-Lead ECG at the study site, whichever occurred first. Patients discontinuing the study without AF were censored at the time of the last available ECG.

Secondary Outcome Measures

Number of Patients With Documented AF Recurrences
Time From Randomization to First Documented and Confirmed AF Recurrence
A confirmed AF recurrence was defined as a documented AF recurrence which was confirmed by a consecutive ECG performed at least 1 hour after first AF documentation.
Number of Patients With Documented and Confirmed AF Recurrences
Time From Randomization to First Documented AF Recurrence in Patients With Sinus Rhythm 48 Hours After Cardioversion
Excluding patients with early relapses (within 48 hours) while the study drug, started after cardioversion, had not yet reached steady-state.
Number of Patients in Sinus Rhythm 48 Hours After Cardioversion With Documented AF Recurrence
Documented AF recurrences in those patients who did not experience early relapses (within 48 hours after cardioversion)

Full Information

First Posted
February 10, 2012
Last Updated
July 29, 2014
Sponsor
Menarini Group
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1. Study Identification

Unique Protocol Identification Number
NCT01534962
Brief Title
Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion
Acronym
RAFFAELLO
Official Title
A Randomised, Double-blind, Double-dummy, Placebo-controlled, Dose-ranging Phase II Study Assessing Ranolazine in the Maintenance of Sinus Rhythm After Electrical Cardioversion in Patients With Non-permanent Atrial Fibrillation.
Study Type
Interventional

2. Study Status

Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
January 2012 (undefined)
Primary Completion Date
October 2013 (Actual)
Study Completion Date
March 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Menarini Group

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Dose-ranging Phase II study testing the efficacy and safety of 3 doses of Ranolazine (low, intermediate and high, given BID) versus placebo in maintaining sinus rhythm after successful electrical cardioversion in patients with persistent atrial fibrillation (AFib). After successful cardioversion and subsequent randomisation, patients report trans-telephonic EGCs on a daily basis to a central core ECG facility. Maximum treatment duration is 112 days (16 weeks).
Detailed Description
Patients with persistent AFib are screened for eligibility and undergo direct current cardioversion (DCC). If DCC is successful (defined as persistence of sinus rhythm 2 h post-DCC) patients meeting all the inclusion criteria and none of the exclusion criteria are randomly assigned to the treatment arms (Ranolazine low, intermediate, high dose or placebo, given BID). Transtelephonic ECG devices (TT-ECG) are used for recording of AFib recurrence to be read by a Central ECG Core Laboratory. Any symptoms indicative of AFib have to be recorded by the patient in a diary. Study Visits are held for screening (Visit 1), at DCC and randomisation (Visit 2), one week post DCC (Visit 3), after 8 weeks of treatment (Visit 4), and at end of treatment (Visit 5). A safety follow-up telephone call is held 2 weeks after end of treatment. 12-Lead ECGs are performed at every visit. Safety evaluations include regular safety laboratory blood and urine tests, 12-lead ECGs and the continuous recording of adverse events. A double-dummy technique is used to ensure double-blind conditions.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Persistent Atrial Fibrillation
Keywords
Atrial Fibrillation, Ranolazine, Arrhythmias, Cardiac, Antiarrhythmic Agents, Cardiac Electroversion, Ranexa

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
241 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ranolazine low dose
Arm Type
Experimental
Arm Description
Ranolazine, low dose, oral, BID
Arm Title
Ranolazine intermediate dose
Arm Type
Experimental
Arm Description
Ranolazine, intermediate dose, oral, BID
Arm Title
Ranolazin high dose
Arm Type
Experimental
Arm Description
Ranolazine, high dose, oral, BID
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo (sugar pill), oral, BID.
Intervention Type
Drug
Intervention Name(s)
Ranolazine
Other Intervention Name(s)
Ranexa (R)
Intervention Description
Oral administration, BID; for a maximum of 112 days.
Intervention Type
Drug
Intervention Name(s)
Ranolazine
Other Intervention Name(s)
Ranexa (R)
Intervention Description
Oral administration, BID; for a maximum of 112 days.
Intervention Type
Drug
Intervention Name(s)
Ranolazine
Other Intervention Name(s)
Ranexa (R)
Intervention Description
Oral administration, BID; for a maximum of 112 days.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sugar pill
Intervention Description
Oral administration, BID; for a maximum of 112 days.
Primary Outcome Measure Information:
Title
Time From Randomization to First Documented AF Recurrence.
Description
Time to first AF recurrence reported by patient-reported TT-ECG or 12-Lead ECG at the study site, whichever occurred first. Patients discontinuing the study without AF were censored at the time of the last available ECG.
Time Frame
16 weeks (112 days)
Secondary Outcome Measure Information:
Title
Number of Patients With Documented AF Recurrences
Time Frame
16 weeks (112 days)
Title
Time From Randomization to First Documented and Confirmed AF Recurrence
Description
A confirmed AF recurrence was defined as a documented AF recurrence which was confirmed by a consecutive ECG performed at least 1 hour after first AF documentation.
Time Frame
16 weeks (112 days)
Title
Number of Patients With Documented and Confirmed AF Recurrences
Time Frame
16 weeks (112 days)
Title
Time From Randomization to First Documented AF Recurrence in Patients With Sinus Rhythm 48 Hours After Cardioversion
Description
Excluding patients with early relapses (within 48 hours) while the study drug, started after cardioversion, had not yet reached steady-state.
Time Frame
16 weeks (112 days)
Title
Number of Patients in Sinus Rhythm 48 Hours After Cardioversion With Documented AF Recurrence
Description
Documented AF recurrences in those patients who did not experience early relapses (within 48 hours after cardioversion)
Time Frame
16 weeks (112 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female patients 18 years and older Patients with persistent AF suitable for electrical direct current cardioversion (DCC) A female of childbearing potential may be enrolled providing she has a negative pregnancy test at baseline and is routinely using an effective method of birth control resulting in a low failure rate until end of study Able to give written informed consent before any study related procedure Able to attend all the visits scheduled in the study Exclusion Criteria: Patients with first diagnosed AF or patients with paroxysmal AF Patients with long-standing persistent AF or permanent AF Patients having known concurrent temporary secondary causes of AF such as alcohol intoxication, pulmonary embolism, hyperthyroidism, pneumonia, hypoxemia, acute pericarditis or myocarditis Patients having undergone atrial catheter ablation for AF Patients carrying a pacemaker Patients with electrolytes imbalances that may cause cardiac arrhythmias, e.g. potassium < 3.5 mmol/L or > 5.5 mmol/L Patients with any contra-indications to Ranexa according to the drug-specific product characteristics Patients taking class I or Class III antiarrhythmic agents within 3 days of planned randomisation Patients taking beta-blockers unless used on stable doses for at least 2 weeks prior to the planned randomisation. Single doses of Intravenous beta-blockers are allowed up to 10 hours from the planned randomisation Patients taking Dronedarone or oral Amiodarone within 2 weeks and 3 months of planned randomisation, respectively Patients with a history of ECG abnormalities that in the opinion of the Investigator render the subject unsuitable for the trial, including history of congenital or a family history of long QT syndrome and a QTc interval ≥500 msec at Screening Patients with congestive heart failure NYHA grade III and IV; Patients with any serious intercurrent illness (including psychiatric and neurological disorders) which, in the opinion of the Investigator, is incompatible with the protocol. Patients taking Metformin at a total daily dose greater than 1000 mg. Patients taking Simvastatin at a total daily dose greater than 20 mg.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alan J Camm, Professor
Organizational Affiliation
Head of Clinical Cardiology; St. Gerorge's University of London, United Kingdom
Official's Role
Study Chair
Facility Information:
Facility Name
Universitätsmedizin Göttingen (UMG), Kardiologie und Pneumologie
City
Goettingen
State/Province
Lower Saxony
ZIP/Postal Code
37075
Country
Germany
Facility Name
FONDAZIONE IRCCS, Dip. Cardiotoracovascolare (U.C.C.)
City
Pavia
State/Province
Lombardy
ZIP/Postal Code
27100
Country
Italy
Facility Name
Hospital Clínic i Provincial de Barcelona, Servicio de Cardiología-Sección de Arritmias
City
Barcelona
State/Province
Catalonia
ZIP/Postal Code
08036
Country
Spain
Facility Name
St. George's University of London
City
London
State/Province
Greater London
ZIP/Postal Code
SW17 0RE
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
25602175
Citation
De Ferrari GM, Maier LS, Mont L, Schwartz PJ, Simonis G, Leschke M, Gronda E, Boriani G, Darius H, Guillamon Toran L, Savelieva I, Dusi V, Marchionni N, Quintana Rendon M, Schumacher K, Tonini G, Melani L, Giannelli S, Alberto Maggi C, Camm AJ; RAFFAELLO Investigators (see Online Supplementary Appendix for List of Participating Centers and Investigators). Ranolazine in the treatment of atrial fibrillation: Results of the dose-ranging RAFFAELLO (Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion) study. Heart Rhythm. 2015 May;12(5):872-8. doi: 10.1016/j.hrthm.2015.01.021. Epub 2015 Jan 17.
Results Reference
derived

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Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion

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