Intravenous Cardioversion of Atrial Fibrillation (AF) With AZD1305

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

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

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: AZD1305
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>AZD1305 iv infusion | Drug: AZD1305<br>* 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<br>|
| Placebo Comparator: 2<br>Placebo iv infusion | Drug: Placebo<br>* iv single infusion given intravenously until successful conversion of Atrial Fibrillation (AF) to Sinus Rhythm (SR) occur or for a maximum of 30 minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| 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 | 
| 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 | 
| 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 | 
| 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. | 
| Maximal Observed Plasma Concentration of AZD1305 | Plasma concentration of AZD1305 | Up to 24 hours following start of study drug infusion | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AZD1305, intravenous cardioversion of Atrial Fibrillation