Intravenous Cardioversion of Atrial Fibrillation (AF) With AZD1305

A Phase 2 study testing AZD1305 in people with Atrial Fibrillation, run by AstraZeneca at 31 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

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. Read more about this study

Who is it for?: Ages 20 to 80 years
Conditions the study is for: Atrial Fibrillation
What is being tested?: AZD1305
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 228 participants
Where: 31 sitesin 8 countries
Study dates: May 2009to Dec 2009
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

Potassium level below 3.8 mmol/L measured in serum or plasma
QTcF interval >440 ms

Trial locations and contacts

31 sites in 8 countries.

Country

City, postcode or hospital

31 sites in 8 countries

Poland6 sites

Research Site
Bytom
Research Site
Lubin
Research Site
Płock
Research Site
Ruda Śląska
Research Site
Torun
Research Site
Warsaw

Other trials in Poland

Hungary5 sites

Research Site
Budapest
Research Site
Cegléd
Research Site
Debrecen
Research Site
Kecskemét
Research Site
Székesfehérvár

Other trials in Hungary

Netherlands4 sites

Research Site
Breda
Research Site
Deventer
Research Site
Leeuwarden
Research Site
Sneek

Other trials in Netherlands

Norway4 sites

Research Site
Hamar
Research Site
Oslo
Research Site
Rud
Research Site
Tromsø

Other trials in Norway

Czechia3 sites

Research Site
Brno, CZ
Research Site
Prague
Research Site
Znojmo

Other trials in Czechia

Denmark3 sites

Research Site
Aalborg
Research Site
Esbjerg
Research Site
Svendborg

Other trials in Denmark

Slovakia3 sites

Research Site
Martin
Research Site
Nitra
Research Site
Ružomberok

Other trials in Slovakia

Sweden3 sites

Research Site
Linköping
Research Site
Örebro
Research Site
Stockholm

Other trials in Sweden

About this study

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

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

Conditions: Atrial Fibrillation
Being tested: AZD1305, Placebo
Keywords: AZD1305, intravenous cardioversion of Atrial Fibrillation
Medical subject headings: Atrial Fibrillation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AZD1305Drug
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
PlaceboDrug
iv single infusion given intravenously until successful conversion of Atrial Fibrillation (AF) to Sinus Rhythm (SR) occur or for a maximum of 30 minutes

Study groups in NCT00915356
Study group	Role	What they receive
1	Experimental	AZD1305 iv infusion Receives: Drug: AZD1305
2	Placebo comparator	Placebo iv infusion Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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
Measured: Within 90 minutes from start of infusion

Secondary outcomes (10)

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).
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: Six hours following start of study drug infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2009Dec 2009

First posted8 Jun 2009 (estimated)
Study startMay 2009
Primary completionDec 2009
Study completionDec 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Atrial FibrillationStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 228 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00915356
Sponsor's protocol ID: D3191C00009
Other IDs: 2009-009862-15 (EudraCT No), 2009
Status last verified: Jan 2012
First submitted: 5 Jun 2009
Last updated: 1 Feb 2012
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 21561900

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruiting
Horizon 360 Protocol for the Treatment of Paroxysmal Atrial Fibrillation With the Sphere-360™ Catheter and Affera™ Mapping and Ablation System (Horizon 360)
Paroxysmal AF
Active, not recruitingObservational study
Concomitant Left Atrial Appendage Closure and Pulsed Field Ablation-Asia
Concomitant Procedures, Atrial Fibrillation
Active, not recruiting
CONVERGE Post-Approval Study (PAS)
Chronic Atrial Fibrillation
Recruiting
Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic Stroke Despite Anticoagulation Therapy
Ischemic Stroke, Atrial Fibrillation
RecruitingPhase 2
Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation
Atrial Fibrillation (AF)

All Atrial Fibrillation trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Double-blind, Randomised, Placebo-controlled, Multicentre, Dose-escalating Study of AZD1305 Given Intravenously for Cardioversion of Atrial Fibrillation
ClinicalTrials.gov ID: NCT00915356
Acronym / sponsor ID: D3191C00009
Conditions: Atrial Fibrillation
Keywords: AZD1305, intravenous cardioversion of Atrial Fibrillation
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 228 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: May 2009
Primary completion: Dec 2009 (actual)
Study completion: Dec 2009 (actual)
First posted: 8 Jun 2009 (estimated)
Results: Posted 1 Feb 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
1	Experimental	Drug: AZD1305AZD1305 iv infusion
2	Placebo comparator	Drug: PlaceboPlacebo iv infusion

Who may qualify

Ages: 20 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (2 listed)

Potassium level below 3.8 mmol/L measured in serum or plasma
QTcF interval >440 ms

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AZD1305Intravenous (iv) single infusion given intravenously until successful conversion of Atrial Fibrillation (AF) to Sinus Rhythm (SR) occur or for a maximum of 30 minutes	Drug	1
Placeboiv single infusion given intravenously until successful conversion of Atrial Fibrillation (AF) to Sinus Rhythm (SR) occur or for a maximum of 30 minutes	Drug	2

Primary outcome

Dose-response Relationship for QTcF Interval of AZD1305
Time frame: At any time post randomisation until end of Holter recording (18-24 hours post start of drug infusion).
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)
Time frame: Within 90 minutes from start of infusion
Conversion of AF to SR with maintenance of SR maintained for at least 1 minute

10 secondary outcomes

Wide QRS Tachycardias
Time frame: From start of study drug infusion until discharge from hospital on study day 2.
Heart Rhythm. Number of Participants With Early Relapse Into AF.
Time frame: 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
Time frame: 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.
Time frame: 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.
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.
Maximal Observed Plasma Concentration of AZD1305
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: Six hours following start of study drug infusion

Results and safety

Results posted to the registry on 1 Feb 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AZD1305 Dose Group 1	26	25
AZD1305 Dose Group 2	45	45
AZD1305 Dose Group 3	45	45
AZD1305 Dose Group 4	12	12
Placebo	43	43

Primary outcome: Dose-response Relationship for QTcF Interval of AZD1305

Time frame: At any time post randomisation until end of Holter recording (18-24 hours post start of drug infusion).. Mean (95% Confidence Interval). Unit: ms

Measure	AZD1305 Dose Group 1 n = 25	AZD1305 Dose Group 2 n = 45	AZD1305 Dose Group 3 n = 45	AZD1305 Dose Group 4 n = 12	Placebo n = 42
Value	461 (449 to 474)	486 (476 to 495)	490 (480 to 499)	482 (464 to 500)	440 (430 to 450)

Primary outcome: Conversion of Atrial Fibrillation (AF) and Maintenance of Sinus Rhytm (SR)

Time frame: Within 90 minutes from start of infusion. Number (95% Confidence Interval). Unit: Percentage of patients converted to SR

Measure	AZD1305 Dose Group 1 n = 26	AZD1305 Dose Group 2 n = 45	AZD1305 Dose Group 3 n = 45	AZD1305 Dose Group 4 n = 12	Placebo n = 43
Value	7.7 (0.9 to 25.1)	17.8 (8.0 to 32.1)	37.8 (23.8 to 53.5)	50.0 (21.1 to 78.9)	0.0 (0.0 to 8.2)

10 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AZD1305 Dose Group 1	1 of ?	5 of 26 (19.2%)	Not reported
AZD1305 Dose Group 2	3 of ?	9 of 45 (20%)	Not reported
AZD1305 Dose Group 3	3 of ?	8 of 45 (17.8%)	Not reported
AZD1305 Dose Group 4	1 of ?	3 of 12 (25%)	Not reported
Placebo	2 of ?	5 of 43 (11.6%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 21561900Ronaszeki 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.

Related trials for Atrial Fibrillation

Active, not recruiting
Horizon 360 Protocol for the Treatment of Paroxysmal Atrial Fibrillation With the Sphere-360™ Catheter and Affera™ Mapping and Ablation System (Horizon 360)
Paroxysmal AF
Active, not recruitingObservational study
Concomitant Left Atrial Appendage Closure and Pulsed Field Ablation-Asia
Concomitant Procedures, Atrial Fibrillation
Active, not recruiting
CONVERGE Post-Approval Study (PAS)
Chronic Atrial Fibrillation
Recruiting
Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic Stroke Despite Anticoagulation Therapy
Ischemic Stroke, Atrial Fibrillation
RecruitingPhase 2
Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation
Atrial Fibrillation (AF)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

AZD1305 Medical Science Director study director

AstraZeneca R&D, Mölndal, Sweden

Aladár Rónaszéki principal investigator

Péterfy HospitalDepartment of Cardiology1076 Budapest, Péterfi Sándor str. 8-20HUNGARY

31 sites in 8 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AZD1305 in people with Atrial Fibrillation, run by AstraZeneca at 31 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in Poland, Hungary, Netherlands, Norway, Czechia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Feb 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-response Relationship for QTcF Interval of AZD1305 (time frame: At any time post randomisation until end of Holter recording (18-24 hours post start of drug infusion).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00915356, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2012.