Clinical trial NCT00526136: Vernakalant (Oral) Prevention of Atrial Fibrillation Recurrence Post-Conversion Study
Official title: Vernakalant (Oral) Prevention of Atrial Fibrillation Recurrence Post-Conversion Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atrial Fibrillation
Keywords: Atrial Fibrillation
Lead sponsor: Advanz Pharma
Sponsor class: INDUSTRY
First posted: 2007-09-10
Enrollment: 735
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: To evaluate the safety, tolerability and efficacy of 3 doses of vernakalant (oral) (150 mg, 300 mg and 500 mg b.i.d.) administered for up to 90 days in subjects with sustained symptomatic atrial fibrillation (AF duration \> 72 hours and \< 6 months).


Eligibility criteria: Inclusion Criteria:

* Comprehend and sign a written informed consent form, (per local and national regulations, as applicable)
* Be 18 to 85 years of age
* Women must not be pregnant, be non-nursing and if pre-menopausal, must be using an effective form of birth control from time of screening until 3 months after the last dose of medication. Methods of birth control considered to be effective may include hormonal contraception (the pill), an intrauterine device (IUD), condoms in combination with a spermicidal cream, total abstinence or sterilisation. Men should be advised not to conceive a child and are advised to use an effective form of birth control from admission until 3 months after the last dose of study medication
* Have symptomatic AF that has been sustained for greater than 72 hours and less than 6 months duration and is clinically indicated for cardioversion;
* Have adequate anticoagulant therapy for cardioversion in accordance with standard of practice as recommended by ACC/AHA/ESC guidelines (Fuster V. et al, 2006);
* Be haemodynamically stable (100 mmHg \< systolic blood pressure \< 190 mmHg) at screening and on Day 1 before dosing (while taking rate control drugs, if required). After resting supine for 3 minutes, blood pressures should be measured 3 times in 5 minutes with at least 1 minute between assessments;
* Have a body weight between 45 and 113 kg (99 and 250 lbs).

Exclusion Criteria:

* Have known prolonged QT syndrome or QTcB interval of \>0.500 sec as measured at screening on a 12 lead ECG; familial long QT syndrome; previous Torsades de Pointes; ventricular fibrillation; or sustained ventricular tachycardia (VT).
* Have a QRS \>0.140 sec;
* Documented previous episodes of second or third-degree atrioventricular block;
* Have clinically significant persistent bradycardia with ventricular rate below 50 beats/min, sick-sinus syndrome or pacemaker;
* Have clinically significant moderate or severe aortic valvular stenosis (gradient \>25 mmHg), hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy or constrictive pericarditis;
* Have Class III or Class IV congestive heart failure at screening or admission, or have been hospitalized for heart failure in the previous 6 months;
* Have a myocardial infarction (MI), cardiac surgery, angioplasty, unstable angina or acute coronary syndrome within 30 days prior to entry into the study; h) Have serious pulmonary, hepatic, metabolic, renal (serum creatinine \> 2.0 mg/dl), gastrointestinal, central nervous system (CNS) or psychiatric disease, end-stage disease states, or any other disease that could interfere with the conduct or validity of the study or compromise subject safety;
* Have known concurrent temporary secondary causes of AF such as alcohol intoxication, pulmonary embolism, hyperthyroidism, pneumonia, hypoxemia (oxygen saturation \< 90% on room air), acute pericarditis, or myocarditis;
* Potassium (K+) \<3.5 mmol/L or \>5.5 mmol/L or magnesium (Mg2+) below the lower limit of normal (Mg2+\< 0.65 mmol/L in subjects 65 years or younger and \<0.80 mmol/L in subjects 66 years or older). (Both K+ and Mg2+ should be corrected prior to dosing);
* Have clinical evidence of digoxin toxicity;
* Have received an oral Class I or Class III antiarrhythmic agent (including sotalol) within 3 days of randomisation or oral amiodarone within 4 weeks, or have received intravenous Class I or Class III antiarrhythmic agent or i.v. amiodarone within 24 hours prior to start of dosing;
* Have any other surgical or medical condition that, in the judgment of the clinical Investigator might warrant exclusion or be contraindicated for safety reasons;
* Be concurrently participating in another drug study or have received an investigational drug within 30 days prior to screening;
* Be unable to communicate well with the Investigator and to comply with the requirements of the entire study;

Primary outcomes:
measure: Time to first documented recurrence of symptomatic sustained AF.
timeFrame: Time to first documented recurrence of symptomatic sustained AF within Day 90 of dosing
measure: Safety assessments- Vital signs, safety laboratory assays, ECG parameters, physical examinations, and frequency of adverse events
timeFrame: Safety assessments within Day 120 of dosing
Secondary outcomes:
measure: Time to first documented recurrence of symptomatic or asymptomatic sustained AF
timeFrame: Time to first documented recurrence of symptomatic or asymptomatic sustained AF within 90 days of dosing
measure: Time to first documented recurrence of symptomatic AF
timeFrame: Time to first documented recurrence of symptomatic AF within 90 days of dosing
measure: Time to first documented recurrence of symptomatic or asymptomatic AF
timeFrame: Time to first documented recurrence of symptomatic or asymptomatic AF within 90 days of dosing
measure: Proportion of subjects in sinus rhythm on Day 90.
timeFrame: Proportion of subjects in sinus rhythm on Day 90 of dosing
measure: Improvement in AF symptoms as assessed by an AF symptom checklist.
timeFrame: Improvement in AF symptoms as assessed by an AF symptom checklist within Day 90 of dosing
measure: Improvement in QOL as measured by SF-36
timeFrame: Improvement in QOL as measured by SF-36 within Day 90 of dosing
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Hobart
country: Australia
facility: Royal Hobart Hospital
city: Launceston
country: Australia
facility: Launceston General Hospital
city: Woodville
country: Australia
facility: Queen Elizabeth Hospital
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Antwerp
country: Belgium
facility: A. Z. Middelheim
city: Bonheiden
country: Belgium
facility: Imelda Ziekenhuis
city: Leuven
country: Belgium
facility: U. Z. Gasthuisberg
city: Roeselare
country: Belgium
facility: Heilig Hart Ziekenhuis
city: Haskovo
country: Bulgaria
facility: MHAT - Haskovo
city: Pleven
country: Bulgaria
facility: UMHAT 'Dr. Georgi Stranski'
city: Rousse
country: Bulgaria
facility: MHAT 'Rouse AD'
city: Sofia
country: Bulgaria
facility: IV MHAT
city: Sofia
country: Bulgaria
facility: MHAT 'Tzaritza Yoanna'
city: Sofia
country: Bulgaria
facility: MI Central Clinical Base - Ministry of Interior
city: Sofia
country: Bulgaria
facility: Military Medical Academy
city: Varna
country: Bulgaria
facility: MHAT 'Sveta Marina'
city: Varna
country: Bulgaria
facility: MMA - Hospital Base for Active Treatment - Varna
city: Zadar
country: Croatia
facility: General Hospital Zadar
city: Zagreb
country: Croatia
facility: Clinical Hospital Dubrava
city: Zagreb
country: Croatia
facility: General Hospital Sveti Duh
city: Zagreb
country: Croatia
facility: University Hospital " Merkur "
city: Jindrichuv Hradec
country: Czech Republic
facility: Nemocnice Jindrichuv Hradec, a.s.
city: Kromeriz
country: Czech Republic
facility: Kromerizska Nemocnice, a.s.
city: Kutna Hora
country: Czech Republic
facility: Nemocnice Kutna Hora s.r.o.
city: Plzen
country: Czech Republic
facility: Fakultni Nemocnice Plzen
city: Praha
country: Czech Republic
facility: Vojenska Nemocnice Praha
city: Praha
country: Czech Republic
facility: Vseobecna Fakultni Nemocnice v Praze
city: Pribram
country: Czech Republic
facility: Oblastni Nemocnice Pribram, a.s.
city: Semily
country: Czech Republic
facility: Nemocnice v Semilech
city: Slany
country: Czech Republic
facility: Nemocnice Slany
city: Tabor
country: Czech Republic
facility: Nemocnice Tabor, a.s.
city: Trebic
country: Czech Republic
facility: Nemocnice Trebic, p.o.
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
city: Frederiksberg
country: Denmark
facility: Frederiksberg Hospital
city: Hellerup
country: Denmark
facility: Gentofte Amtssygehus
city: Hjorring
country: Denmark
facility: Sygehus Vendsyssel - Hjørring
city: Koge
country: Denmark
facility: Region Sjælland Sygehus øst Køge
city: Kolding
country: Denmark
facility: Kolding Sygehus
city: Haabneeme
country: Estonia
facility: Viimsi Hospital
city: Parnu
country: Estonia
facility: Pärnu Hospital
city: Tallinn
country: Estonia
facility: North Estonia Regional Hospital
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Bad Krozingen
country: Germany
facility: Herzzentrum Bad Krozingen
city: Bad Nauheim
country: Germany
facility: Kerckhoff-Klinik Forschungsgesellschaft mbH
city: Witten
country: Germany
facility: Evangelisches Krankenhaus
city: Ajka
country: Hungary
facility: Magyar Imre Hospital
city: Baja
country: Hungary
facility: Baja City Community Hospital
city: Budapest
country: Hungary
facility: Nyiro Gyula Hospital
city: Budapest
country: Hungary
facility: Péterfy Sándor Hospital
city: Budapest
country: Hungary
facility: Szent Istvan Hospital
city: Gyongyos
country: Hungary
facility: Bugat Pal Hospital
city: Gyor
country: Hungary
facility: Petz Aladár County Teaching Hospital
city: Kecskemet
country: Hungary
facility: Bacs-Kiskun County Hospital
city: Szekesfehervar
country: Hungary
facility: Fejér Megyei Szent György Kórház
city: Szolnok
country: Hungary
facility: Hetenyi Geza County Hospital
city: Zalaegerszeg
country: Hungary
facility: Zala County Hospital
city: Kaunas
country: Lithuania
facility: Kaunas Medical University Hospital
city: Klaipeda
country: Lithuania
facility: Klaipeda Seamen's Hospital
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santariskiu Clinic
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
city: Delft
country: Netherlands
facility: Reinier de Graaf Groep
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Nieuwegein
country: Netherlands
facility: Stichting Sint Antonius Ziekenhuis
city: Zwolle
country: Netherlands
facility: Isala Klinieken
city: Auckland
country: New Zealand
facility: North Shore Hospital
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Nelson
country: New Zealand
facility: Nelson Hospital
city: Bydgoszcz
country: Poland
facility: SZZOZ Wielospecjalityczny Szpital Miejski im. Dr. E.Warminsk
city: Chrzanow
country: Poland
facility: Szpital Powiatowy
city: Gdansk
country: Poland
facility: Instytut Kardiologii AMG
city: Gdynia
country: Poland
facility: Szpital Miejski w Gdyni
city: Lodz
country: Poland
facility: Zaklad Farmakologii i Terapii Monitorowanej z Oddzialem Chor
city: Lublin
country: Poland
facility: SP ZOZ Okregowy Szpital Kolejowy
city: Rzeszow
country: Poland
facility: Szpital Wojewodzki Nr 2
city: Szczecin
country: Poland
facility: Klinika Kardiologii PAM
city: Tarnow
country: Poland
facility: Szpital Specjalistyczny
city: Warsaw
country: Poland
facility: III Klinika Chorob Wewnetrznych i Kardiologii
city: Warsaw
country: Poland
facility: Wojskowy Instytut Medyczny, CSK MON
city: Wroclaw
country: Poland
facility: Osrodek Chorob Serca, 4Wojskowy Szpital Kliniczny z Poliklin
city: Amadora
country: Portugal
facility: Hospital Fernando da Fonseca
city: Lisbon
country: Portugal
facility: Hospital de Santa Marta
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar Vila Nova de Gaia
city: Arad
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Arad
city: Brasov
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Brasov
city: Bucuresti
country: Romania
facility: Institutul de Cardiologie C.C. Iliescu
city: Bucuresti
country: Romania
facility: Spitalul Clinic Colentina
city: Bucuresti
country: Romania
facility: Spitalul Clinic de Urgenta Sf. Pantelimon
city: Lasi
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Sf. Spiridon Iasi
city: Oradea
country: Romania
facility: Spitalul Clinic Judetean Oradea
city: Ploiesti
country: Romania
facility: Spitalul Judetean de Urgenta Ploiesti
city: Targu Mures
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Targu Mures
city: Timisoara
country: Romania
facility: Spitalul Clinic Municipal de Urgenta Timisoara
city: Moscow
country: Russian Federation
facility: FSI EMC of the President of RF, b.o. City Hospital #51
city: Moscow
country: Russian Federation
facility: MedCentre of RF President, Central Clinical Hospital
city: Moscow
country: Russian Federation
facility: Moscow City Hospital # 29
city: Moscow
country: Russian Federation
facility: Moscow Medical Academy. City Hospital #20
city: Moscow
country: Russian Federation
facility: Moscow SHI City Clinical Hospital #52
city: Moscow
country: Russian Federation
facility: RMA of Postg. education b.o. Botkin City Clinical Hospital
city: Moscow
country: Russian Federation
facility: Russian Cardiology Research Centre
city: Moscow
country: Russian Federation
facility: War Veteran's Hospital #3
city: St Petersburg
country: Russian Federation
facility: Pokrovskaya City Hospital
city: St Petersburg
country: Russian Federation
facility: St- Petersburg GUZ City Hospital #15
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl Regional Clinical Hospital
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl State Medical Academy b.o. Clinical Hospital #2
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Dedinje Cardiovascular Institute
city: Belgrade
country: Serbia
facility: Institute of CV Diseases, Clinical Center of Serbia
city: Niska Banja
country: Serbia
facility: Clinical Center for Cardiovascular Diseases
city: Sremska Kamenica
country: Serbia
facility: Institute of Cardiovascular Diseases Sremska Kamenica
city: Zemun
country: Serbia
facility: Clinical Center Bezanijska Kosa
city: Zemun
country: Serbia
facility: Clinical Center Zemun
city: Singapore
country: Singapore
facility: National Heart Center
city: Bratislava
country: Slovakia
facility: FNsP Bratislava - Pracovisko Stare Mesto
city: Bratislava
country: Slovakia
facility: Slovensky Ustav Srdcovocievnych Chorob
city: Kosice
country: Slovakia
facility: Vychodoslovensky Ustav Srdcovocievnych Chorob
city: Nitra
country: Slovakia
facility: Fakultna Nemocnica Nitra
city: Nove Zamky
country: Slovakia
facility: FNsP Nove Zamky
city: Presov
country: Slovakia
facility: FNsP J. A. Reimana
city: Kempton Park
country: South Africa
facility: Clinresco Centres (Pty) Ltd
city: Somerset West
country: South Africa
facility: Vergelegen Medi-Clinic
city: Worcester
country: South Africa
facility: Clinical Project Research
city: Barcelona
country: Spain
facility: Hospital Vall D'Hebron
city: Granada
country: Spain
facility: Hosp. Virgen de las Nieves
city: Madrid
country: Spain
facility: Clinica Universitaria Puerta de Hierro
city: Madrid
country: Spain
facility: Hosp. Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Tarragona
country: Spain
facility: Hospital Univ. Tarragona Joan XXIII
city: Malmo
country: Sweden
facility: Universitetssjukhuset Malmö
city: Orebro
country: Sweden
facility: Universitetssjukhuset Örebro
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Basel
country: Switzerland
facility: Universitaetsspital Basel
city: Liestal
country: Switzerland
facility: Kantonsspital Liestal
city: Lugano
country: Switzerland
facility: Cardio Centro Ticino
city: St Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: Dnepropetrovsk
country: Ukraine
facility: Reg.Diag.Center of Dnepr.
city: Donetsk
country: Ukraine
facility: Cent.City Clin.Hosp.#3.Chair of Int.Dis.#2 of Donetsk SMU
city: Donetsk
country: Ukraine
facility: Donetsk Regional Clinical Hospital
city: Kharkov
country: Ukraine
facility: City Clinical Hospital #8
city: Kiev
country: Ukraine
facility: City Clinical Hospital #1
city: Kiev
country: Ukraine
facility: Kiev City Clinical Hospital No 5, Coronary Care Unit
city: Kiev
country: Ukraine
facility: Kiev Clinical Emergency Care Hospital
city: Kiev
country: Ukraine
facility: M.D.Strazhesko Institut of Cardiology
city: Kiev
country: Ukraine
facility: N.D. Strazhesko Institute of Cardiology
city: Lugansk
country: Ukraine
facility: Lugansk First Clinical Multiprofile Hospital #1, cardiology
city: Lviv
country: Ukraine
facility: Lviv Reg St Clinical Treat-and-Diagn Cardio. Centre
city: Odessa
country: Ukraine
facility: City Clinical Hospital #9
city: Zaporizhzhya
country: Ukraine
facility: Hospital Therapy Dept #1of Zaporozhye SMU
Study officials:
affiliation: Advanz Pharma
name: Gregory Beatch, PhD
role: STUDY_DIRECTOR
References:
citation: Torp-Pedersen C, Raev DH, Dickinson G, Butterfield NN, Mangal B, Beatch GN. A randomized, placebo-controlled study of vernakalant (oral) for the prevention of atrial fibrillation recurrence after cardioversion. Circ Arrhythm Electrophysiol. 2011 Oct;4(5):637-43. doi: 10.1161/CIRCEP.111.962340. Epub 2011 Aug 14.