Clinical trial NCT01534962: Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Persistent Atrial Fibrillation
Keywords: Atrial Fibrillation
Ranolazine
Arrhythmias, Cardiac
Antiarrhythmic Agents
Cardiac Electroversion
Ranexa
Lead sponsor: Menarini Group
Sponsor class: INDUSTRY
First posted: 2012-02-17
Enrollment: 241
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Time From Randomization to First Documented AF Recurrence.
timeFrame: 16 weeks (112 days)
Secondary outcomes:
measure: Number of Patients With Documented AF Recurrences
timeFrame: 16 weeks (112 days)
measure: Time From Randomization to First Documented and Confirmed AF Recurrence
timeFrame: 16 weeks (112 days)
measure: Number of Patients With Documented and Confirmed AF Recurrences
timeFrame: 16 weeks (112 days)
measure: Time From Randomization to First Documented AF Recurrence in Patients With Sinus Rhythm 48 Hours After Cardioversion
timeFrame: 16 weeks (112 days)
measure: Number of Patients in Sinus Rhythm 48 Hours After Cardioversion With Documented AF Recurrence
timeFrame: 16 weeks (112 days)
Other outcomes:
Locations:
city: Goettingen
country: Germany
facility: Universitätsmedizin Göttingen (UMG), Kardiologie und Pneumologie
state: Lower Saxony
city: Pavia
country: Italy
facility: FONDAZIONE IRCCS, Dip. Cardiotoracovascolare (U.C.C.)
state: Lombardy
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial de Barcelona, Servicio de Cardiología-Sección de Arritmias
state: Catalonia
city: London
country: United Kingdom
facility: St. George's University of London
state: Greater London
Study officials:
affiliation: Head of Clinical Cardiology; St. Gerorge's University of London, United Kingdom
name: Alan J Camm, Professor
role: STUDY_CHAIR
References:
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.