Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion

Persistent Atrial Fibrillation Clinical Trial

— 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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01534962
• Other study ID #: RAF-01
• Secondary ID: 2011-002789-18
• Status: Completed
• Phase: Phase 2
• First received: February 10, 2012
• Last updated: July 29, 2014
• Start date: January 2012
• Est. completion date: March 2014

Study information

• Verified date: July 2014
• Source: Menarini Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesItaly: The Italian Medicines AgencySpain: Agencia Española de Medicamentos y Productos SanitariosUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 241
• Est. completion date: March 2014
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Fibrillation
• Persistent Atrial Fibrillation

Intervention

Drug:
• Ranolazine
Oral administration, BID; for a maximum of 112 days.
• Ranolazine
Oral administration, BID; for a maximum of 112 days.
• Ranolazine
Oral administration, BID; for a maximum of 112 days.
• Placebo
Oral administration, BID; for a maximum of 112 days.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Menarini Group

Countries where clinical trial is conducted

Germany,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	16 weeks (112 days)	No
Secondary	Number of Patients With Documented AF Recurrences		16 weeks (112 days)	No
Secondary	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.	16 weeks (112 days)	No
Secondary	Number of Patients With Documented and Confirmed AF Recurrences		16 weeks (112 days)	No
Secondary	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.	16 weeks (112 days)	No
Secondary	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)	16 weeks (112 days)	No