CompletedNCT01534962RAFFAELLOUpdated Aug 19, 2014Results posted

Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion

A Phase 2 interventional study of Ranolazine and Ranolazine in Persistent Atrial Fibrillation, sponsored by Menarini Group. Completed at 4 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-08-19.

Sponsored by Menarini Group · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 241
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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).

Read the 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.

Conditions studied

Persistent Atrial Fibrillation

Browse trials for

Atrial Fibrillation 3,870

Keywords

Atrial Fibrillation
Ranolazine
Arrhythmias, Cardiac
Antiarrhythmic Agents
Cardiac Electroversion
Ranexa

In context

Atrial Fibrillation

3,870 studies on the registry are indexed under Atrial Fibrillation; 924 are open to participants now.

This study's enrollment of 241 is above the median of 144 across 2,380 interventional studies indexed under Atrial Fibrillation.

Browse Atrial Fibrillation studies →

Lead sponsor

Menarini Group is the lead sponsor of 27 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 241 participants (actual)

Study arms

Experimental
Ranolazine low dose
Ranolazine, low dose, oral, BID
Drug: Ranolazine
Experimental
Ranolazine intermediate dose
Ranolazine, intermediate dose, oral, BID
Drug: Ranolazine
Experimental
Ranolazin high dose
Ranolazine, high dose, oral, BID
Drug: Ranolazine
Placebo comparator
Placebo
Placebo (sugar pill), oral, BID.
Drug: Placebo

Interventions

DrugRanolazine
Oral administration, BID; for a maximum of 112 days.
Also known as: Ranexa (R)
DrugRanolazine
Oral administration, BID; for a maximum of 112 days.
Also known as: Ranexa (R)
DrugRanolazine
Oral administration, BID; for a maximum of 112 days.
Also known as: Ranexa (R)
DrugPlacebo
Oral administration, BID; for a maximum of 112 days.
Also known as: Sugar pill

What researchers measure

Primary outcomes

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.
Time frame: 16 weeks (112 days)

Secondary outcomes

Number of Patients With Documented AF Recurrences
Time frame: 16 weeks (112 days)
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.
Time frame: 16 weeks (112 days)
Number of Patients With Documented and Confirmed AF Recurrences
Time frame: 16 weeks (112 days)
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.
Time frame: 16 weeks (112 days)
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)
Time frame: 16 weeks (112 days)

Results

Posted Aug 19, 2014

Limitations and caveats

Most of the Kaplan-Meier estimates could not be calculated due to the lower than expected number of observed events and the high variability of data.

Participant flow

Participant flow — Overall Study
Milestone	Ranolazine Low Dose	Ranolazine Intermediate Dose	Ranolazin High Dose	Placebo
Started	67	60	58	56
Completed	30	34	34	24
Not completed	37	26	24	32
Withdrew: Randomized but did not start treatment	2	0	0	1
Withdrew: Discontinued at af recurrence	35	26	24	31

Outcome measures

PrimaryTime 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.

Time frame:: 16 weeks (112 days)
Reported as:: Median · Days

Time From Randomization to First Documented AF Recurrence.
Days	Ranolazine Low Dose	Ranolazine Intermediate Dose	Ranolazin High Dose	Placebo
Time From Randomization to First Documented AF Recurrence.	51.0 (9.0 to NA)	NA (68.0 to NA)	117.0 (17.0 to NA)	58.0 (16.0 to NA)

SecondaryNumber of Patients With Documented AF Recurrences

Time frame:: 16 weeks (112 days)
Reported as:: Number · participants

Number of Patients With Documented AF Recurrences
participants	Ranolazine Low Dose	Ranolazine Intermediate Dose	Ranolazin High Dose	Placebo
Number of Patients With Documented AF Recurrences	37	25	23	31

SecondaryTime 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.

Time frame:: 16 weeks (112 days)
Reported as:: Median · Days

Time From Randomization to First Documented and Confirmed AF Recurrence
Days	Ranolazine Low Dose	Ranolazine Intermediate Dose	Ranolazin High Dose	Placebo
Time From Randomization to First Documented and Confirmed AF Recurrence	73.0 (11.0 to NA)	NA (NA to NA)	NA (117.0 to NA)	NA (38.0 to NA)

SecondaryNumber of Patients With Documented and Confirmed AF Recurrences

Time frame:: 16 weeks (112 days)
Reported as:: Number · participants

Number of Patients With Documented and Confirmed AF Recurrences
participants	Ranolazine Low Dose	Ranolazine Intermediate Dose	Ranolazin High Dose	Placebo
Number of Patients With Documented and Confirmed AF Recurrences	31	19	16	24

SecondaryTime 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.

Time frame:: 16 weeks (112 days)
Reported as:: Median · Days

Time From Randomization to First Documented AF Recurrence in Patients With Sinus Rhythm 48 Hours After Cardioversion
Days	Ranolazine Low Dose	Ranolazine Intermediate Dose	Ranolazin High Dose	Placebo
Time From Randomization to First Documented AF Recurrence in Patients With Sinus Rhythm 48 Hours After Cardioversion	56.0 (11.0 to NA)	NA (98.0 to NA)	117.0 (18.0 to NA)	78.0 (37.0 to NA)

SecondaryNumber 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)

Time frame:: 16 weeks (112 days)
Reported as:: Number · participants

Number of Patients in Sinus Rhythm 48 Hours After Cardioversion With Documented AF Recurrence
participants	Ranolazine Low Dose	Ranolazine Intermediate Dose	Ranolazin High Dose	Placebo
Number of Patients in Sinus Rhythm 48 Hours After Cardioversion With Documented AF Recurrence	32	19	21	27

Adverse events

Collected over 16 weeks (112 days). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Ranolazine Low Dose	—	2/65 (3.1%)	51/65 (78.5%)
Ranolazine Intermediate Dose	—	3/60 (5%)	46/60 (76.7%)
Ranolazin High Dose	—	3/58 (5.2%)	42/58 (72.4%)
Placebo	—	4/55 (7.3%)	41/55 (74.5%)

Most frequent serious events

Showing 10 of 18

Most frequent serious events
Event	Ranolazine Low Dose	Ranolazine Intermediate Dose	Ranolazin High Dose	Placebo
Angina PectorisCardiac disorders	0/65	1/60	0/58	1/55
Atrial FibrillationCardiac disorders	0/65	0/60	0/58	1/55
Sick Sinus SyndromeCardiac disorders	0/65	0/60	0/58	1/55
Ventricular TachycardiaCardiac disorders	0/65	0/60	0/58	1/55
Sudden DeathGeneral disorders	0/65	0/60	0/58	1/55
HypertensionVascular disorders	1/65	0/60	0/58	1/55
Atrial FlutterCardiac disorders	0/65	0/60	1/58	0/55
AnaemiaBlood and lymphatic system disorders	0/65	0/60	1/58	0/55
SyncopeNervous system disorders	0/65	0/60	1/58	0/55
EpistaxisRespiratory, thoracic and mediastinal disorders	0/65	0/60	1/58	0/55

Most frequent other events

Showing 10 of 14

Most frequent other events
Event	Ranolazine Low Dose	Ranolazine Intermediate Dose	Ranolazin High Dose	Placebo
Atrial FibrillationCardiac disorders	29/65	24/60	23/58	27/55
DizzinessNervous system disorders	6/65	2/60	14/58	7/55
PalpitationsCardiac disorders	9/65	11/60	11/58	6/55
FatigueGeneral disorders	11/65	10/60	9/58	5/55
Chest PainGeneral disorders	8/65	7/60	4/58	6/55
DyspnoeaRespiratory, thoracic and mediastinal disorders	5/65	7/60	5/58	6/55
AstheniaGeneral disorders	4/65	1/60	5/58	2/55
HeadacheNervous system disorders	2/65	2/60	5/58	2/55
NauseaGastrointestinal disorders	5/65	1/60	4/58	0/55
VertigoEar and labyrinth disorders	1/65	1/60	4/58	2/55

Baseline characteristics

ITT-population (excluding 3 randomized patients who never started study drug)

Age, Continuous
Age, Continuous(years)	Ranolazine Low Dose	Ranolazine Intermediate Dose	Ranolazin High Dose	Placebo	Total
Mean	66.9 ± 11.8	65.5 ± 8.5	63.6 ± 11.3	65.2 ± 9.5	65.3 ± 10.4

Sex: Female, Male
Sex: Female, Male(Participants)	Ranolazine Low Dose	Ranolazine Intermediate Dose	Ranolazin High Dose	Placebo	Total
Female	19	9	12	14	54
Male	46	51	46	41	184

Time since AF diagnosis
Time since AF diagnosis(months)	Ranolazine Low Dose	Ranolazine Intermediate Dose	Ranolazin High Dose	Placebo	Total
Mean	10.5 ± 24.0	7.2 ± 12.9	15.5 ± 28.2	6.9 ± 13.5	10.0 ± 20.7

Study locations

4 sites

Universitätsmedizin Göttingen (UMG), Kardiologie und Pneumologie
Goettingen, Lower Saxony 37075, Germany
FONDAZIONE IRCCS, Dip. Cardiotoracovascolare (U.C.C.)
Pavia, Lombardy 27100, Italy
Hospital Clínic i Provincial de Barcelona, Servicio de Cardiología-Sección de Arritmias
Barcelona, Catalonia 08036, Spain
St. George's University of London
London, Greater London SW17 0RE, United Kingdom

References and documents

Publications

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. PubMed 25602175 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 19, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01534962
Lead sponsor: Menarini Group
Responsible party: Sponsor
First posted: Feb 17, 2012
Start date: Jan 2012
Primary completion: Oct 2013
Completion: Mar 2014
Results posted: Aug 19, 2014
Last update: Aug 19, 2014

Study contacts

Alan J Camm, Professor

study chair · Head of Clinical Cardiology; St. Gerorge's University of London, United Kingdom

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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