Persistent Atrial FibrillationPhase 2RAFFAELLONCT01534962
Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion
A Phase 2 study testing Ranolazine in people with Persistent Atrial Fibrillation, run by Menarini Group at 4 sites in 4 countries.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Persistent Atrial Fibrillation
- What is being tested?
- Ranolazine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 241 participants
- Where
- 4 sitesin 4 countries
- Study dates
- Jan 2012to Mar 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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.
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
Germany1 site
Universitätsmedizin Göttingen (UMG), Kardiologie und Pneumologie
Göttingen, Lower Saxony, 37075
Italy1 site
FONDAZIONE IRCCS, Dip. Cardiotoracovascolare (U.C.C.)
Pavia, Lombardy, 27100
Spain1 site
Hospital Clínic i Provincial de Barcelona, Servicio de Cardiología-Sección de Arritmias
Barcelona, Catalonia, 08036
United Kingdom1 site
St. George's University of London
London, Greater London, SW17 0RE
About this study
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.
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
- Persistent Atrial Fibrillation
- Being tested
- Ranolazine, Placebo
- Keywords
- Atrial Fibrillation, Ranolazine, Arrhythmias, Cardiac, Antiarrhythmic Agents, Cardiac Electroversion, Ranexa
- Medical subject headings
- Atrial Fibrillation, Arrhythmias, Cardiac
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RanolazineDrug
Also called Ranexa (R)
Oral administration, BID; for a maximum of 112 days.
RanolazineDrug
Also called Ranexa (R)
Oral administration, BID; for a maximum of 112 days.
RanolazineDrug
Also called Ranexa (R)
Oral administration, BID; for a maximum of 112 days.
PlaceboDrug
Also called Sugar pill
Oral administration, BID; for a maximum of 112 days.
| Study group | Role | What they receive |
|---|---|---|
| Ranolazine low dose | Experimental | Ranolazine, low dose, oral, BID Receives: Drug: Ranolazine |
| Ranolazine intermediate dose | Experimental | Ranolazine, intermediate dose, oral, BID Receives: Drug: Ranolazine |
| Ranolazin high dose | Experimental | Ranolazine, high dose, oral, BID Receives: Drug: Ranolazine |
| Placebo | Placebo comparator | Placebo (sugar pill), oral, BID. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 16 weeks (112 days)
Secondary outcomes (5)
Number of Patients With Documented AF Recurrences
Measured: 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.
Measured: 16 weeks (112 days)
Number of Patients With Documented and Confirmed AF Recurrences
Measured: 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.
Measured: 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)
Measured: 16 weeks (112 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2012 (estimated)
- Study startJan 2012
- Primary completionOct 2013
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Persistent Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 241 participants (actual)
Sponsor and investigators
- Lead sponsor
- Menarini Group
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alan J Camm, Professor, Study chair, Head of Clinical Cardiology; St. Gerorge's University of London, United Kingdom
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01534962
- Sponsor's protocol ID
- RAF-01
- Other IDs
- 2011-002789-18
- Acronym
- RAFFAELLO
- Status last verified
- Jul 2014
- First submitted
- 10 Feb 2012
- Last updated
- 19 Aug 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01534962
- Acronym / sponsor ID
- RAFFAELLO / RAF-01
- Conditions
- Persistent Atrial Fibrillation
- Keywords
- Atrial Fibrillation, Ranolazine, Arrhythmias, Cardiac, Antiarrhythmic Agents, Cardiac Electroversion, Ranexa
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 241 participants (actual)
- Lead sponsor
- Menarini GroupIndustry (pharma, biotech, devices)
- Study start
- Jan 2012
- Primary completion
- Oct 2013 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 17 Feb 2012 (estimated)
- Results
- Posted 19 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Ranolazine low dose | Experimental | Drug: RanolazineRanolazine, low dose, oral, BID |
| Ranolazine intermediate dose | Experimental | Drug: RanolazineRanolazine, intermediate dose, oral, BID |
| Ranolazin high dose | Experimental | Drug: RanolazineRanolazine, high dose, oral, BID |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo (sugar pill), oral, BID. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RanolazineAlso: Ranexa (R)Oral administration, BID; for a maximum of 112 days. | Drug | Ranolazine low dose |
| RanolazineAlso: Ranexa (R)Oral administration, BID; for a maximum of 112 days. | Drug | Ranolazine intermediate dose |
| RanolazineAlso: Ranexa (R)Oral administration, BID; for a maximum of 112 days. | Drug | Ranolazin high dose |
| PlaceboAlso: Sugar pillOral administration, BID; for a maximum of 112 days. | Drug | Placebo |
Primary outcome
Time From Randomization to First Documented AF Recurrence.
Time frame: 16 weeks (112 days)
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.
5 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
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
Time frame: 16 weeks (112 days)
Number of Patients in Sinus Rhythm 48 Hours After Cardioversion With Documented AF Recurrence
Time frame: 16 weeks (112 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25602175De 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alan J Camm, Professor study chair
Head of Clinical Cardiology; St. Gerorge's University of London, United Kingdom
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ranolazine in people with Persistent Atrial Fibrillation, run by Menarini Group at 4 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Germany, Italy, Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time From Randomization to First Documented AF Recurrence. (time frame: 16 weeks (112 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01534962, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2014.