Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion (RAFFAELLO)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Menarini Group
ClinicalTrials.gov Identifier:
NCT01534962
First received: February 10, 2012
Last updated: July 29, 2014
Last verified: July 2014
  Purpose

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).


Condition Intervention Phase
Persistent Atrial Fibrillation
Drug: Ranolazine
Drug: Placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Menarini Group:

Primary Outcome Measures:
  • Time From Randomization to First Documented AF Recurrence. [ Time Frame: 16 weeks (112 days) ] [ Designated as safety issue: No ]

    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 Frame: 16 weeks (112 days) ] [ Designated as safety issue: No ]
  • Time From Randomization to First Documented and Confirmed AF Recurrence [ Time Frame: 16 weeks (112 days) ] [ Designated as safety issue: No ]
    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 Frame: 16 weeks (112 days) ] [ Designated as safety issue: No ]
  • Time From Randomization to First Documented AF Recurrence in Patients With Sinus Rhythm 48 Hours After Cardioversion [ Time Frame: 16 weeks (112 days) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 16 weeks (112 days) ] [ Designated as safety issue: No ]
    Documented AF recurrences in those patients who did not experience early relapses (within 48 hours after cardioversion)


Enrollment: 241
Study Start Date: January 2012
Study Completion Date: March 2014
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ranolazine low dose
Ranolazine, low dose, oral, BID
Drug: Ranolazine
Oral administration, BID; for a maximum of 112 days.
Other Name: Ranexa (R)
Experimental: Ranolazine intermediate dose
Ranolazine, intermediate dose, oral, BID
Drug: Ranolazine
Oral administration, BID; for a maximum of 112 days.
Other Name: Ranexa (R)
Experimental: Ranolazin high dose
Ranolazine, high dose, oral, BID
Drug: Ranolazine
Oral administration, BID; for a maximum of 112 days.
Other Name: Ranexa (R)
Placebo Comparator: Placebo
Placebo (sugar pill), oral, BID.
Drug: Placebo
Oral administration, BID; for a maximum of 112 days.
Other Name: Sugar pill

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01534962

Locations
Germany
Universitätsmedizin Göttingen (UMG), Kardiologie und Pneumologie
Goettingen, Lower Saxony, Germany, 37075
Italy
FONDAZIONE IRCCS, Dip. Cardiotoracovascolare (U.C.C.)
Pavia, Lombardy, Italy, 27100
Spain
Hospital Clínic i Provincial de Barcelona, Servicio de Cardiología-Sección de Arritmias
Barcelona, Catalonia, Spain, 08036
United Kingdom
St. George's University of London
London, Greater London, United Kingdom, SW17 0RE
Sponsors and Collaborators
Menarini Group
Investigators
Study Chair: Alan J Camm, Professor Head of Clinical Cardiology; St. Gerorge's University of London, United Kingdom
  More Information

No publications provided

Responsible Party: Menarini Group
ClinicalTrials.gov Identifier: NCT01534962     History of Changes
Other Study ID Numbers: RAF-01, 2011-002789-18
Study First Received: February 10, 2012
Results First Received: July 29, 2014
Last Updated: July 29, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Menarini Group:
Atrial Fibrillation
Ranolazine
Arrhythmias, Cardiac
Antiarrhythmic Agents
Cardiac Electroversion
Ranexa

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Ranolazine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014