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Intravenous Cardioversion of Atrial Fibrillation (AF) With AZD1305

Primary Purpose

Atrial Fibrillation

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AZD1305
Placebo
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atrial Fibrillation focused on measuring AZD1305, intravenous cardioversion of Atrial Fibrillation

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

1

2

Arm Description

AZD1305 iv infusion

Placebo iv infusion

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

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).
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.
Heart Rhythm. Number of Patients Remaining in SR up to 24 h 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
Study the Relationship Between Systemic Exposure and Response, With Special Regards to Conversion of AF to SR and the Effect on the QTcF Interval.
Maximal Observed Plasma Concentration of AZD1305
Plasma concentration of AZD1305
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 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 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.
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

Full Information

First Posted
June 5, 2009
Last Updated
January 2, 2012
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT00915356
Brief Title
Intravenous Cardioversion of Atrial Fibrillation (AF) With AZD1305
Official Title
A Double-blind, Randomised, Placebo-controlled, Multicentre, Dose-escalating Study of AZD1305 Given Intravenously for Cardioversion of Atrial Fibrillation
Study Type
Interventional

2. Study Status

Record Verification Date
January 2012
Overall Recruitment Status
Completed
Study Start Date
May 2009 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
December 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation
Keywords
AZD1305, intravenous cardioversion of Atrial Fibrillation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
228 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
AZD1305 iv infusion
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Placebo iv infusion
Intervention Type
Drug
Intervention Name(s)
AZD1305
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
iv single infusion given intravenously until successful conversion of Atrial Fibrillation (AF) to Sinus Rhythm (SR) occur or for a maximum of 30 minutes
Primary Outcome Measure Information:
Title
Dose-response Relationship for QTcF Interval of AZD1305
Description
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
Time Frame
At any time post randomisation until end of Holter recording (18-24 hours post start of drug infusion).
Title
Conversion of Atrial Fibrillation (AF) and Maintenance of Sinus Rhytm (SR)
Description
Conversion of AF to SR with maintenance of SR maintained for at least 1 minute
Time Frame
Within 90 minutes from start of infusion
Secondary Outcome Measure Information:
Title
Wide QRS Tachycardias
Description
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).
Time Frame
From start of study drug infusion until discharge from hospital on study day 2.
Title
Heart Rhythm. Number of Participants With Early Relapse Into AF.
Description
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.
Time Frame
Within 5 minutes following investigational product (IP) induced conversion, or direct current (DC) cardioversion, of AF to SR
Title
Heart Rhythm. Number of Patients Remaining in SR up to 24 h Following Start of Study Drug Infusion
Time Frame
During 24 hours following start of study drug infusion
Title
Heart Rhythm. Number of Patients Remaining in SR up to 13 to 18 Days Following Study Drug Infusion.
Description
Number of patients in SR at day 13-18
Time Frame
During 13 to 18 days following study drug infusion
Title
Study the Relationship Between Systemic Exposure and Response, With Special Regards to Conversion of AF to SR and the Effect on the QTcF Interval.
Time Frame
Since this study is no longer intended to be part of any marketing authorisation application, the analyses addressing this objective were not conducted.
Title
Maximal Observed Plasma Concentration of AZD1305
Description
Plasma concentration of AZD1305
Time Frame
Up to 24 hours following start of study drug infusion
Title
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
Time Frame
Conversion from AF to SR within 90 minutes from start of infusion
Title
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.
Description
Subgroup analysis for patients with duration of current AF episode 8 days - 30 days. Number of patients converting from AF to SR.
Time Frame
Conversion from AF to SR within 90 minutes from start of infusion
Title
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
Description
Subgroup analysis for patients with duration of current AF episode 31 days - 3 months. Number of patients converting from AF to SR.
Time Frame
Conversion from AF to SR within 90 minutes from start of infusion
Title
Percentage of Patients, Discharged Within 6 h (QTcF ≤500 ms) After Start of Infusion
Description
Percentage, with 95% confidence interval, of patients with QTcF≤500 ms six hours following start of study drug infusion
Time Frame
Six hours following start of study drug infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
AZD1305 Medical Science Director
Organizational Affiliation
AstraZeneca R&D, Mölndal, Sweden
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Aladár Rónaszéki
Organizational Affiliation
Péterfy HospitalDepartment of Cardiology1076 Budapest, Péterfi Sándor str. 8-20HUNGARY
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Brno
State/Province
CZ
Country
Czech Republic
Facility Name
Research Site
City
Praha 2
Country
Czech Republic
Facility Name
Research Site
City
Znojmo
Country
Czech Republic
Facility Name
Research Site
City
Aalborg
Country
Denmark
Facility Name
Research Site
City
Esbjerg
Country
Denmark
Facility Name
Research Site
City
Svendborg
Country
Denmark
Facility Name
Research Site
City
Budapest
Country
Hungary
Facility Name
Research Site
City
Cegled
Country
Hungary
Facility Name
Research Site
City
Debrecen
Country
Hungary
Facility Name
Research Site
City
Kecskemet
Country
Hungary
Facility Name
Research Site
City
Szekesfehervar
Country
Hungary
Facility Name
Research Site
City
Breda
Country
Netherlands
Facility Name
Research Site
City
Deventer
Country
Netherlands
Facility Name
Research Site
City
Leeuwarden
Country
Netherlands
Facility Name
Research Site
City
Sneek
Country
Netherlands
Facility Name
Research Site
City
Hamar
Country
Norway
Facility Name
Research Site
City
Oslo
Country
Norway
Facility Name
Research Site
City
RUD
Country
Norway
Facility Name
Research Site
City
Tromso
Country
Norway
Facility Name
Research Site
City
Bytom
Country
Poland
Facility Name
Research Site
City
Lubin
Country
Poland
Facility Name
Research Site
City
Plock
Country
Poland
Facility Name
Research Site
City
Ruda Slaska
Country
Poland
Facility Name
Research Site
City
Torun
Country
Poland
Facility Name
Research Site
City
Warszawa
Country
Poland
Facility Name
Research Site
City
Martin
Country
Slovakia
Facility Name
Research Site
City
Nitra
Country
Slovakia
Facility Name
Research Site
City
Ruzomberok
Country
Slovakia
Facility Name
Research Site
City
Linkoping
Country
Sweden
Facility Name
Research Site
City
Orebro
Country
Sweden
Facility Name
Research Site
City
Stockholm
Country
Sweden

12. IPD Sharing Statement

Citations:
PubMed Identifier
21561900
Citation
Ronaszeki A, Alings M, Egstrup K, Gaciong Z, Hranai M, Kiraly C, Sereg M, Figatowski W, Bondarov P, Johansson S, Frison L, Edvardsson N, Berggren A. Pharmacological cardioversion of atrial fibrillation--a double-blind, randomized, placebo-controlled, multicentre, dose-escalation study of AZD1305 given intravenously. Europace. 2011 Aug;13(8):1148-56. doi: 10.1093/europace/eur120. Epub 2011 May 11.
Results Reference
derived

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Intravenous Cardioversion of Atrial Fibrillation (AF) With AZD1305

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