Back to resultsEvaluation of Fondaparinux in Patients With a Heart Rhythm Disturbance Who Undergo Restoration of Normal Heart Rhythm
Primary Purpose
Fibrillation, Atrial
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
fondaparinux
unfractionated heparin
Vitamin-K-Antagonist
Sponsored by
About this trial
This is an interventional prevention trial for Fibrillation, Atrial focused on measuring Cardioversion, Electric, Pathological Conditions, Sings and Symptoms, Cardiovascular Diseases, Heart Diseases, Atrial Fibrillation, Arrhythmias, Cardiac, Pathologic Processes, Anticoagulants
Eligibility Criteria
Inclusion Criteria:
- Male or female patients aged at least 18 years with atrial fibrillation (AF) meeting at least one of the following criteria (a, b, c): a. Acute clinical symptoms (like palpitations, chest pain, dyspnea, fatigue, lightheadedness, or syncope) for at least 48 hours and AF on baseline ECG b. Newly discovered AF persisting for >=7 days c. Recurrent AF persisting for >=7 days
Exclusion Criteria:
- No documented sinus rhythm on ECG for more than 1 year
- Acute neurological deficits (TIA, stroke, intracranial bleeding), or known disease which may cause neurological deficits (e.g., multiple sclerosis, seizure disorder)
- Treatment with antithrombotic agents, including low-dose anticoagulation, for more than 48 hours prior to randomisation
- Treatment with oral NSAIDs or ASA at doses greater than 325 mg per day for more than 72 hours prior to randomisation
- Anticoagulant therapy required or likely to be required during the study period
- Treatment with ASA at a dose greater than 325 mg per day or oral NSAIDs (at any dose) required or likely to be required during the study period
- Treatment with two or more antiplatelet agents (e.g. clopidogrel and ASA) at any dose at the same time (i.e., within 24 hours)
- Known hypersensitivity to UFH, VKA, or Fondaparinux or one of these drugs' excipients
- Active, clinically significant bleeding or clinically significant bleeding within the past month
- Major surgery within the previous three months
- Uncontrolled arterial hypertension (persistent systolic blood pressure over 180 mm Hg or diastolic blood pressure over 110 mm Hg)
- Bacterial endocarditis
- Calculated creatinine clearance < 30 mL/min
- Body weight < 50 kg
- Planned surgery or intervention within the next 65 days
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Arm 1: fondaparinux
Arm 2: unfractionated heparin + Vitamin-K-Antagonist
Arm Description
Outcomes
Primary Outcome Measures
Number of Participants With at Least One Event of Cerebral Neurologic Event, Systemic Thromboembolism, Death From Any Cause, and/or Major Bleeding Until the End of Treatment (EOT) Plus 4 Days
Cerebral neurologic events are defined as any new neurologic disorders caused by cerebrovascular embolization, e.g., Transient Ischemic Attack (TIA), cerebral infarction. The cerebrovascular origin of the event has to be confirmed by objective procedures. Systemic thromboembolism comprises any arterial thromboembolic event (e.g., peripheral vascular embolism, mesenteric infarct, or myocardial infarction). All cerebral neurologic events were adjudicated by a Central Adjudication Committee (CAC), members of which were unaware of the participants' treatment assignment.
Secondary Outcome Measures
Number of Thrombus-negative and Thrombus-positive Participants (Par.) With at Least One Cerebral Neurologic Event
Cerebral neurologic events are defined as any new neurologic disorders caused by cerebrovascular embolisation, e.g., TIA, cerebral infarction. All cerebral neurologic events were adjudicated by a CAC, members of which were unaware of the participants' treatment assignment.The cerebrovascular origin of the event was confirmed by objective procedures. A thrombus or blood clot is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system (i.e., clotting factors).
Number of Thrombus-negative and Thrombus-positive Participants With at Least One Systemic Thromboembolism
Systemic thromboembolism comprises any arterial thromboembolic event (e.g., peripheral vascular embolism, mesenteric infarct, or myocardial infarction). All systemic thromboembolic events were adjudicated by a CAC, the members of which were unaware of the participants' treatment assignment. A thrombus or blood clot is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system (i.e., clotting factors).
Number of Thrombus-negative and Thrombus-positive Participants Who Died From Any Cause
The cause of death was classified as due to a thromboembolic event (like cerebral infarction), bleeding, or other established diagnosis, or as unexplained. All deaths were adjudicated by an independent CAC, the members of which were unaware of the participants' treatment assignment. A thrombus or blood clot is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system (i.e., clotting factors).
Number of Thrombus-negative and Thrombus-positive Participants With at Least One Major Bleeding Event
Major bleeding: fatal, and/or symptomatic in a critical area/ organ, causes a fall in hemoglobin of >=3 grams/deciliter compared with the pre-randomization level, or leads to the transfusion of >=2 units of whole blood/red blood cells. All bleeding events were adjudicated by a CAC, the members of which were unaware of the participants' treatment assignment. A thrombus/ blood clot is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets, and the activation of the humoral coagulation system (i.e., clotting factors).
Number of Thrombus-negative and Thrombus-positive Participants With at Least One Minor Bleeding Event
Minor bleeding is defined as clinically overt bleeding events that do not meet the criteria for major or clinically relevant non-major bleeding. All episodes of bleeding were adjudicated by an independent CAC, the members of which were unaware of the participants' treatment assignment.
Number of Participants With Primary Successful Electrical Cardioversion (CV) in Sinus Rhythm
CV may be performed electively to restore sinus rhythm in patients with persistent AF. The primary successful electric CV was assessed by a 12- lead electrocardiogram (ECG) directly after the CV. Results of the last cardioversion were used in cases for which more than one CV was performed.
Number of Participants With a Thrombus in the Left Atrium (LA) or in the Left Atrial Appendage (LAA) at the Time of the Second TEE
Atrial fibrillation (AF) causes stagnant blood in the LA or LAA and can lead to a thromboembolism. Stasis in the LAA represents the principal mechanism of thrombus formation in AF.
Number of Thrombus-negative and Thrombus-positive Participants With Conversion to Sinus Rhythm
Sinus rhythm is the normal beating of the heart, as measured by an ECG. Normal sinus rhythm not only indicates that the rhythm is normally generated by the sinus node and is traveling in a normal fashion in the heart, but it also indicates that the heart rate (the rate at which the sinus node is generating impulses) is within normal limits.
Number of Participants Who Were Re-hospitalized
Hospitalization signifies that the participant has been detained (usually involving at least an overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have been appropriate in the physician's office or out-patient setting. Re-hospitalization refers to an event of hospitalization after discharge for the initial hospitilization for the cardioversion.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00911300
Brief Title
Evaluation of Fondaparinux in Patients With a Heart Rhythm Disturbance Who Undergo Restoration of Normal Heart Rhythm
Official Title
An International, Multicentre, Randomised, Open, Controlled, Two-parallel Group, Phase II Pilot Study to Evaluate the Efficacy and Safety of ARIXTRA™ for Anticoagulation of Patients With Atrial Fibrillation Undergoing Electric Cardioversion Following Transesophageal Echocardiography
Study Type
Interventional
2. Study Status
Record Verification Date
September 2012
Overall Recruitment Status
Completed
Study Start Date
August 2009 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
September 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
5. Study Description
Brief Summary
The purpose of this study is to test whether Fondaparinux is effective and safe to prevent thromboembolic events (like for example strokes) and bleeding events in patients who undergo a normalisation of their heart rhythm disturbance. Fondaparinux will be compared with Heparin and tablets containing Vitamin-K-Antagonists (Phenprocoumon, Fluindione, or Warfarin).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fibrillation, Atrial
Keywords
Cardioversion, Electric, Pathological Conditions, Sings and Symptoms, Cardiovascular Diseases, Heart Diseases, Atrial Fibrillation, Arrhythmias, Cardiac, Pathologic Processes, Anticoagulants
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
349 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1: fondaparinux
Arm Type
Active Comparator
Arm Title
Arm 2: unfractionated heparin + Vitamin-K-Antagonist
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
fondaparinux
Intervention Description
Comparison of different drugs
Intervention Type
Drug
Intervention Name(s)
unfractionated heparin
Intervention Description
Comparison of different drugs
Intervention Type
Drug
Intervention Name(s)
Vitamin-K-Antagonist
Intervention Description
Comparison of different drugs
Primary Outcome Measure Information:
Title
Number of Participants With at Least One Event of Cerebral Neurologic Event, Systemic Thromboembolism, Death From Any Cause, and/or Major Bleeding Until the End of Treatment (EOT) Plus 4 Days
Description
Cerebral neurologic events are defined as any new neurologic disorders caused by cerebrovascular embolization, e.g., Transient Ischemic Attack (TIA), cerebral infarction. The cerebrovascular origin of the event has to be confirmed by objective procedures. Systemic thromboembolism comprises any arterial thromboembolic event (e.g., peripheral vascular embolism, mesenteric infarct, or myocardial infarction). All cerebral neurologic events were adjudicated by a Central Adjudication Committee (CAC), members of which were unaware of the participants' treatment assignment.
Time Frame
Baseline (Day 1) until Day 64 (4 days after the EOT [i.e., last administration of study drug]) for CP participants; Baseline until Day 36 (4 days after the EOT) for CN participants
Secondary Outcome Measure Information:
Title
Number of Thrombus-negative and Thrombus-positive Participants (Par.) With at Least One Cerebral Neurologic Event
Description
Cerebral neurologic events are defined as any new neurologic disorders caused by cerebrovascular embolisation, e.g., TIA, cerebral infarction. All cerebral neurologic events were adjudicated by a CAC, members of which were unaware of the participants' treatment assignment.The cerebrovascular origin of the event was confirmed by objective procedures. A thrombus or blood clot is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system (i.e., clotting factors).
Time Frame
Baseline (Day 1) until Day 64 (4 days after the EOT [i.e., last administration of study drug]) for CP participants; Baseline until Day 36 (4 days after the EOT) for CN participants; and from Baseline until the follow-up visit (FU) (Day 90+/-7)
Title
Number of Thrombus-negative and Thrombus-positive Participants With at Least One Systemic Thromboembolism
Description
Systemic thromboembolism comprises any arterial thromboembolic event (e.g., peripheral vascular embolism, mesenteric infarct, or myocardial infarction). All systemic thromboembolic events were adjudicated by a CAC, the members of which were unaware of the participants' treatment assignment. A thrombus or blood clot is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system (i.e., clotting factors).
Time Frame
Baseline (Day 1) until Day 64 (4 days after the EOT [i.e., last administration of study drug]) for CP participants; Baseline until Day 36 (4 days after the EOT) for CN participants; and from Baseline until the follow-up visit (FU) (Day 90+/-7)
Title
Number of Thrombus-negative and Thrombus-positive Participants Who Died From Any Cause
Description
The cause of death was classified as due to a thromboembolic event (like cerebral infarction), bleeding, or other established diagnosis, or as unexplained. All deaths were adjudicated by an independent CAC, the members of which were unaware of the participants' treatment assignment. A thrombus or blood clot is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system (i.e., clotting factors).
Time Frame
Baseline (Day 1) until Day 64 (4 days after the EOT [i.e., last administration of study drug]) for CP participants; Baseline until Day 36 (4 days after the EOT) for CN participants; and from Baseline until the follow-up visit (FU) (Day 90+/-7)
Title
Number of Thrombus-negative and Thrombus-positive Participants With at Least One Major Bleeding Event
Description
Major bleeding: fatal, and/or symptomatic in a critical area/ organ, causes a fall in hemoglobin of >=3 grams/deciliter compared with the pre-randomization level, or leads to the transfusion of >=2 units of whole blood/red blood cells. All bleeding events were adjudicated by a CAC, the members of which were unaware of the participants' treatment assignment. A thrombus/ blood clot is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets, and the activation of the humoral coagulation system (i.e., clotting factors).
Time Frame
Baseline (Day 1) until Day 64 (4 days after the EOT [i.e., last administration of study drug]) for CP participants; Baseline until Day 36 (4 days after the EOT) for CN participants; and from Baseline until the follow-up visit (FU) (Day 90+/-7)
Title
Number of Thrombus-negative and Thrombus-positive Participants With at Least One Minor Bleeding Event
Description
Minor bleeding is defined as clinically overt bleeding events that do not meet the criteria for major or clinically relevant non-major bleeding. All episodes of bleeding were adjudicated by an independent CAC, the members of which were unaware of the participants' treatment assignment.
Time Frame
Baseline (Day 1) until Day 64 (4 days after the EOT [i.e., last administration of study drug]) for CP participants; Baseline until Day 36 (4 days after the EOT) for CN participants; and from Baseline until the follow-up visit (FU) (Day 90+/-7)
Title
Number of Participants With Primary Successful Electrical Cardioversion (CV) in Sinus Rhythm
Description
CV may be performed electively to restore sinus rhythm in patients with persistent AF. The primary successful electric CV was assessed by a 12- lead electrocardiogram (ECG) directly after the CV. Results of the last cardioversion were used in cases for which more than one CV was performed.
Time Frame
Day 1 until Day 3
Title
Number of Participants With a Thrombus in the Left Atrium (LA) or in the Left Atrial Appendage (LAA) at the Time of the Second TEE
Description
Atrial fibrillation (AF) causes stagnant blood in the LA or LAA and can lead to a thromboembolism. Stasis in the LAA represents the principal mechanism of thrombus formation in AF.
Time Frame
At second TEE (at Day 28+/-4)
Title
Number of Thrombus-negative and Thrombus-positive Participants With Conversion to Sinus Rhythm
Description
Sinus rhythm is the normal beating of the heart, as measured by an ECG. Normal sinus rhythm not only indicates that the rhythm is normally generated by the sinus node and is traveling in a normal fashion in the heart, but it also indicates that the heart rate (the rate at which the sinus node is generating impulses) is within normal limits.
Time Frame
Baseline (Day 1) until Day 64 (4 days after the EOT [i.e., last administration of study drug]) for CP participants; Baseline until Day 36 (4 days after the EOT) for CN participants; and from Day 64 until the follow-up visit (FU) (Day 90+/-7)
Title
Number of Participants Who Were Re-hospitalized
Description
Hospitalization signifies that the participant has been detained (usually involving at least an overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have been appropriate in the physician's office or out-patient setting. Re-hospitalization refers to an event of hospitalization after discharge for the initial hospitilization for the cardioversion.
Time Frame
Baseline (Day 1) until Day 64 (4 days after the EOT [i.e., last administration of study drug]) for CP participants; Baseline until Day 36 (4 days after the EOT) for CN participants; and from Baseline until the follow-up visit (FU) (Day 90+/-7)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female patients aged at least 18 years with atrial fibrillation (AF) meeting at least one of the following criteria (a, b, c): a. Acute clinical symptoms (like palpitations, chest pain, dyspnea, fatigue, lightheadedness, or syncope) for at least 48 hours and AF on baseline ECG b. Newly discovered AF persisting for >=7 days c. Recurrent AF persisting for >=7 days
Exclusion Criteria:
No documented sinus rhythm on ECG for more than 1 year
Acute neurological deficits (TIA, stroke, intracranial bleeding), or known disease which may cause neurological deficits (e.g., multiple sclerosis, seizure disorder)
Treatment with antithrombotic agents, including low-dose anticoagulation, for more than 48 hours prior to randomisation
Treatment with oral NSAIDs or ASA at doses greater than 325 mg per day for more than 72 hours prior to randomisation
Anticoagulant therapy required or likely to be required during the study period
Treatment with ASA at a dose greater than 325 mg per day or oral NSAIDs (at any dose) required or likely to be required during the study period
Treatment with two or more antiplatelet agents (e.g. clopidogrel and ASA) at any dose at the same time (i.e., within 24 hours)
Known hypersensitivity to UFH, VKA, or Fondaparinux or one of these drugs' excipients
Active, clinically significant bleeding or clinically significant bleeding within the past month
Major surgery within the previous three months
Uncontrolled arterial hypertension (persistent systolic blood pressure over 180 mm Hg or diastolic blood pressure over 110 mm Hg)
Bacterial endocarditis
Calculated creatinine clearance < 30 mL/min
Body weight < 50 kg
Planned surgery or intervention within the next 65 days
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Albi
ZIP/Postal Code
81000
Country
France
Facility Name
GSK Investigational Site
City
Antony cedex
ZIP/Postal Code
92166
Country
France
Facility Name
GSK Investigational Site
City
Brest Cedex
ZIP/Postal Code
29609
Country
France
Facility Name
GSK Investigational Site
City
Créteil
ZIP/Postal Code
94000
Country
France
Facility Name
GSK Investigational Site
City
Evecquemont
ZIP/Postal Code
78740
Country
France
Facility Name
GSK Investigational Site
City
Montpellier Cedex 5
ZIP/Postal Code
34295
Country
France
Facility Name
GSK Investigational Site
City
Paris cedex 12
ZIP/Postal Code
75571
Country
France
Facility Name
GSK Investigational Site
City
Paris cedex 13
ZIP/Postal Code
75651
Country
France
Facility Name
GSK Investigational Site
City
Pau
ZIP/Postal Code
64046
Country
France
Facility Name
GSK Investigational Site
City
Pessac cedex
ZIP/Postal Code
33604
Country
France
Facility Name
GSK Investigational Site
City
Poitiers cedex
ZIP/Postal Code
86021
Country
France
Facility Name
GSK Investigational Site
City
Rennes Cedex 9
ZIP/Postal Code
35033
Country
France
Facility Name
GSK Investigational Site
City
Toulouse Cedex 09
ZIP/Postal Code
31059
Country
France
Facility Name
GSK Investigational Site
City
Toulouse cedex 3
ZIP/Postal Code
31076
Country
France
Facility Name
GSK Investigational Site
City
Freiburg
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
79106
Country
Germany
Facility Name
GSK Investigational Site
City
Aschaffenburg
State/Province
Bayern
ZIP/Postal Code
63739
Country
Germany
Facility Name
GSK Investigational Site
City
Bad Toelz
State/Province
Bayern
ZIP/Postal Code
83646
Country
Germany
Facility Name
GSK Investigational Site
City
Simbach a. Inn
State/Province
Bayern
ZIP/Postal Code
84359
Country
Germany
Facility Name
GSK Investigational Site
City
Potsdam
State/Province
Brandenburg
ZIP/Postal Code
14467
Country
Germany
Facility Name
GSK Investigational Site
City
Frankfurt
State/Province
Hessen
ZIP/Postal Code
60488
Country
Germany
Facility Name
GSK Investigational Site
City
Kassel
State/Province
Hessen
ZIP/Postal Code
34121
Country
Germany
Facility Name
GSK Investigational Site
City
Kassel
State/Province
Hessen
ZIP/Postal Code
34125
Country
Germany
Facility Name
GSK Investigational Site
City
Hagenow
State/Province
Mecklenburg-Vorpommern
ZIP/Postal Code
19230
Country
Germany
Facility Name
GSK Investigational Site
City
Bielefeld
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
33604
Country
Germany
Facility Name
GSK Investigational Site
City
Bonn
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
53115
Country
Germany
Facility Name
GSK Investigational Site
City
Bonn
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
53127
Country
Germany
Facility Name
GSK Investigational Site
City
Duisburg-Huckingen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
47259
Country
Germany
Facility Name
GSK Investigational Site
City
Unna
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
59423
Country
Germany
Facility Name
GSK Investigational Site
City
Wesel
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
46483
Country
Germany
Facility Name
GSK Investigational Site
City
Magdeburg
State/Province
Sachsen-Anhalt
ZIP/Postal Code
39120
Country
Germany
Facility Name
GSK Investigational Site
City
Pirna
State/Province
Sachsen
ZIP/Postal Code
01796
Country
Germany
Facility Name
GSK Investigational Site
City
Berlin
ZIP/Postal Code
10249
Country
Germany
Facility Name
GSK Investigational Site
City
Berlin
ZIP/Postal Code
10405
Country
Germany
Facility Name
GSK Investigational Site
City
Berlin
ZIP/Postal Code
13353
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
Evaluation of Fondaparinux in Patients With a Heart Rhythm Disturbance Who Undergo Restoration of Normal Heart Rhythm
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