Vernakalant (Oral) Prevention of Atrial Fibrillation Recurrence Post-Conversion Study

Atrial Fibrillation Clinical Trial

Official title:

Vernakalant (Oral) Prevention of Atrial Fibrillation Recurrence Post-Conversion Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00526136
• Other study ID #: 1235-SR-202-AF
• Status: Completed
• Phase: Phase 2
• First received: September 5, 2007
• Last updated: December 17, 2008
• Start date: March 2007
• Est. completion date: July 2008

Study information

• Verified date: December 2008
• Source: Cardiome Pharma
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationAustralia: Human Research Ethics CommitteeBelgium: Federal Agency for Medicinal Products and Health ProductsBelgium: Institutional Review BoardBulgaria: Bulgarian Drug AgencyBulgaria: Ministry of HealthCroatia: Ethics CommitteeCroatia: Ministry of Health and Social CareCzech Republic: Ethics CommitteeCzech Republic: State Institute for Drug ControlDenmark: Danish Dataprotection AgencyDenmark: Danish Medicines AgencyDenmark: Ethics CommitteeEstonia: The State Agency of MedicineGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyLithuania: Bioethics CommitteeLithuania: State Medicine Control Agency - Ministry of HealthNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Netherlands: Medical Ethics Review Committee (METC)New Zealand: MedsafePoland: Ministry of HealthPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsPortugal: National Pharmacy and Medicines InstituteRomania: Ministry of Public HealthRomania: National Medicines AgencyRussia: Ethics CommitteeRussia: FSI Scientific Center of Expertise of Medical ApplicationSerbia and Montenegro: Agency for Drugs and Medicinal DevicesSerbia: Ethics CommitteeSingapore: Health Sciences AuthoritySlovakia: State Institute for Drug ControlSouth Africa: Medicines Control CouncilSpain: Ministry of Health and ConsumptionSweden: Medical Products AgencySwitzerland: SwissmedicUkraine: State Pharmacological Center - Ministry of Health
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 735
• Est. completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• Placebo

• Vernakalant (oral)
Vernakalant (oral), 150 mg (b.i.d.) Vernakalant (oral), 300 mg (b.i.d.) Vernakalant (oral), 500 mg (b.i.d.)

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Cardiome Pharma

Countries where clinical trial is conducted

Australia,  Belgium,  Bulgaria,  Croatia,  Czech Republic,  Denmark,  Estonia,  Germany,  Hungary,  Lithuania,  Netherlands,  New Zealand,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Singapore,  Slovakia,  South Africa,  Spain,  Sweden,  Switzerland,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to first documented recurrence of symptomatic sustained AF.		Time to first documented recurrence of symptomatic sustained AF within Day 90 of dosing	No
Primary	Safety assessments- Vital signs, safety laboratory assays, ECG parameters, physical examinations, and frequency of adverse events		Safety assessments within Day 120 of dosing	Yes
Secondary	Time to first documented recurrence of symptomatic or asymptomatic sustained AF		Time to first documented recurrence of symptomatic or asymptomatic sustained AF within 90 days of dosing	No
Secondary	Time to first documented recurrence of symptomatic AF		Time to first documented recurrence of symptomatic AF within 90 days of dosing	No
Secondary	Time to first documented recurrence of symptomatic or asymptomatic AF		Time to first documented recurrence of symptomatic or asymptomatic AF within 90 days of dosing	No
Secondary	Proportion of subjects in sinus rhythm on Day 90.		Proportion of subjects in sinus rhythm on Day 90 of dosing	No
Secondary	Improvement in AF symptoms as assessed by an AF symptom checklist.		Improvement in AF symptoms as assessed by an AF symptom checklist within Day 90 of dosing	No
Secondary	Improvement in QOL as measured by SF-36		Improvement in QOL as measured by SF-36 within Day 90 of dosing	No

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