Intravenous Cardioversion of Atrial Fibrillation (AF) With AZD1305

Atrial Fibrillation Clinical Trial

Official title:

A Double-blind, Randomised, Placebo-controlled, Multicentre, Dose-escalating Study of AZD1305 Given Intravenously for Cardioversion of Atrial Fibrillation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00915356
• Other study ID #: D3191C00009
• Secondary ID: 2009-009862-15 (
• Status: Completed
• Phase: Phase 2
• First received: June 5, 2009
• Last updated: January 2, 2012
• Start date: May 2009
• Est. completion date: December 2009

Study information

• Verified date: January 2012
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCzech Republic: State Institute for Drug ControlDenmark: Danish Medicines AgencyHungary: National Institute of PharmacyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Norway: Norwegian Medicines AgencyPoland: Ministry of HealthSlovakia: State Institute for Drug ControlSweden: Medical Products Agency
• Study type: Interventional

Clinical Trial Summary

This study is being carried out to see which dose of AZD1305 is safe and effective in cardioverting atrial fibrillation into normal heart rhythm.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 228
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

Inclusion Criteria:

• Clinical indication for cardioversion of Atrial Fibrillation, ie a correction of irregular heart rhythm to normal heart rhythm

• Current episode of Atrial Fibrillation (ie irregular heart rhythm) lasting up to 3 months at randomisation

• Adequate anticoagulation according to international guidelines (ACC/AHA/ESC, 2006) or national guidelines

Exclusion Criteria:

• Potassium level below 3.8 mmol/L measured in serum or plasma

• QTcF interval >440 ms

Study Design

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

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• AZD1305
Intravenous (iv) single infusion given intravenously until successful conversion of Atrial Fibrillation (AF) to Sinus Rhythm (SR) occur or for a maximum of 30 minutes
• Placebo
iv single infusion given intravenously until successful conversion of Atrial Fibrillation (AF) to Sinus Rhythm (SR) occur or for a maximum of 30 minutes

Locations

Country	Name	City	State
Czech Republic	Research Site	Brno	CZ
Czech Republic	Research Site	Praha 2
Czech Republic	Research Site	Znojmo
Denmark	Research Site	Aalborg
Denmark	Research Site	Esbjerg
Denmark	Research Site	Svendborg
Hungary	Research Site	Budapest
Hungary	Research Site	Cegled
Hungary	Research Site	Debrecen
Hungary	Research Site	Kecskemet
Hungary	Research Site	Szekesfehervar
Netherlands	Research Site	Breda
Netherlands	Research Site	Deventer
Netherlands	Research Site	Leeuwarden
Netherlands	Research Site	Sneek
Norway	Research Site	Hamar
Norway	Research Site	Oslo
Norway	Research Site	RUD
Norway	Research Site	Tromso
Poland	Research Site	Bytom
Poland	Research Site	Lubin
Poland	Research Site	Plock
Poland	Research Site	Ruda Slaska
Poland	Research Site	Torun
Poland	Research Site	Warszawa
Slovakia	Research Site	Martin
Slovakia	Research Site	Nitra
Slovakia	Research Site	Ruzomberok
Sweden	Research Site	Linkoping
Sweden	Research Site	Orebro
Sweden	Research Site	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Czech Republic,  Denmark,  Hungary,  Netherlands,  Norway,  Poland,  Slovakia,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-response Relationship for QTcF Interval of AZD1305	QTcF-QT interval corrected for the RR interval (the time elapsing between two consecutive R waves in the electrocardiogram (ECG)) using the Fridericia formula.For each of 3 consecutive beats (5 consecutive beats if AF) a manual measurement, preferably in lead V2, of QTend intervals was done.The mean QT values of the 3 consecutive beats (5 consecutive beats if AF) were, together with RR intervals, date & time of the ECG, entered into the eCase Report Form (eCRF).The selected beats had to be marked with calipers and noted together with measured values and calculations on the print-out and signed	At any time post randomisation until end of Holter recording (18-24 hours post start of drug infusion).	Yes
Primary	Conversion of Atrial Fibrillation (AF) and Maintenance of Sinus Rhytm (SR)	Conversion of AF to SR with maintenance of SR maintained for at least 1 minute	Within 90 minutes from start of infusion	No
Secondary	Wide QRS Tachycardias	Number of patients with wide QRS tachycardias, determined as significant arrhythmias by an Adjudication Committee (AC). The AC analysed and classified the occurrence of significant arrhythmias (other than AF or AFl) and pauses based on the 12-lead Holter reports. All pauses (=3 sec) and all wide QRS complex tachycardias (=3 beats, QRS =120 ms, and =120 bpm).	From start of study drug infusion until discharge from hospital on study day 2.	Yes
Secondary	Heart Rhythm. Number of Participants With Early Relapse Into AF.	Early relapse into AF within 5 minutes from obtaining the defined criterion for conversion to SR (i.e.1 minute in SR). Patients never converted are not included in the analysis.	Within 5 minutes following investigational product (IP) induced conversion, or direct current (DC) cardioversion, of AF to SR	Yes
Secondary	Heart Rhythm. Number of Patients Remaining in SR up to 24 h Following Start of Study Drug Infusion		During 24 hours following start of study drug infusion	Yes
Secondary	Heart Rhythm. Number of Patients Remaining in SR up to 13 to 18 Days Following Study Drug Infusion.	Number of patients in SR at day 13-18	During 13 to 18 days following study drug infusion	Yes
Secondary	Study the Relationship Between Systemic Exposure and Response, With Special Regards to Conversion of AF to SR and the Effect on the QTcF Interval.		Since this study is no longer intended to be part of any marketing authorisation application, the analyses addressing this objective were not conducted.	No
Secondary	Maximal Observed Plasma Concentration of AZD1305	Plasma concentration of AZD1305	Up to 24 hours following start of study drug infusion	No
Secondary	Conversion From AF to SR Within 90 Minutes From Start of Infusion in the Subgroup of Patients With Duration of Current AF Episode 10 Hours to 7 Days		Conversion from AF to SR within 90 minutes from start of infusion	No
Secondary	Conversion From AF to SR Within 90 Minutes From Start of Infusion in the Subgroup of Patients With Duration of Current AF Episode 8 Days - 30 Days.	Subgroup analysis for patients with duration of current AF episode 8 days - 30 days. Number of patients converting from AF to SR.	Conversion from AF to SR within 90 minutes from start of infusion	No
Secondary	Conversion From AF to SR Within 90 Minutes From Start of Infusion in the Subgroup of Patients With Duration of Current AF Episode 31 Days - 3 Months	Subgroup analysis for patients with duration of current AF episode 31 days - 3 months. Number of patients converting from AF to SR.	Conversion from AF to SR within 90 minutes from start of infusion	No
Secondary	Percentage of Patients, Discharged Within 6 h (QTcF =500 ms) After Start of Infusion	Percentage, with 95% confidence interval, of patients with QTcF=500 ms six hours following start of study drug infusion	Six hours following start of study drug infusion	Yes