Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion

NCT01534962 | Completed Phase 2 Results

• 2 other identifiers: RAF-012011-002789-18
• Study Type: interventional
• Target: 241
• Locations: 4 countries
• Sites: 4

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).

Conditions

Persistent Atrial Fibrillation

Keywords

Atrial Fibrillation; Ranolazine; Arrhythmias, Cardiac; Antiarrhythmic Agents; Cardiac Electroversion; Ranexa

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (5)

• Number of Patients With Documented AF Recurrences

  16 weeks (112 days)

• Time From Randomization to First Documented and Confirmed AF Recurrence

  16 weeks (112 days)

• Number of Patients With Documented and Confirmed AF Recurrences

  16 weeks (112 days)

• Time From Randomization to First Documented AF Recurrence in Patients With Sinus Rhythm 48 Hours After Cardioversion

  16 weeks (112 days)

• Number of Patients in Sinus Rhythm 48 Hours After Cardioversion With Documented AF Recurrence

  16 weeks (112 days)

Study Arms (4)

Ranolazine low dose

EXPERIMENTAL

Ranolazine, low dose, oral, BID

Drug: Ranolazine

Ranolazine intermediate dose

EXPERIMENTAL

Ranolazine, intermediate dose, oral, BID

Drug: Ranolazine

Ranolazin high dose

EXPERIMENTAL

Ranolazine, high dose, oral, BID

Drug: Ranolazine

Placebo

PLACEBO COMPARATOR

Placebo (sugar pill), oral, BID.

Drug: Placebo

Interventions

Ranolazine DRUG

Oral administration, BID; for a maximum of 112 days.

Also known as: Ranexa (R)

Ranolazine low dose

Placebo DRUG

Oral administration, BID; for a maximum of 112 days.

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Menarini Group: lead

Study Sites (4)

Universitätsmedizin Göttingen (UMG), Kardiologie und Pneumologie

Göttingen, Lower Saxony, 37075, Germany

Location

FONDAZIONE IRCCS, Dip. Cardiotoracovascolare (U.C.C.)

Pavia, Lombardy, 27100, Italy

Location

Hospital Clínic i Provincial de Barcelona, Servicio de Cardiología-Sección de Arritmias

Barcelona, Catalonia, 08036, Spain

Location

St. George's University of London

London, Greater London, SW17 0RE, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 25602175 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation; Arrhythmias, Cardiac

Interventions

Ranolazine; Sugars

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbohydrates

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.

Results Point of Contact

• Title: Angela Capriati MD PhD, Head of Corporate Clinical Research
• Organization: Menarini Ricerche S.p.A

acapriati@menarini-ricerche.it

00390555680

Study Officials

• Alan J Camm, Professor

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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2012
• First Posted: February 17, 2012
• Study Start: January 1, 2012
• Primary Completion: October 1, 2013
• Study Completion: March 1, 2014
• Last Updated: August 19, 2014
• Results First Posted: August 19, 2014

Record last verified: 2014-07

Locations

IT (1); ES (1); GB (1); DE (1)