Fibrillation, Atrial
Conditions
Keywords
Cardioversion, Electric, Pathological Conditions, Sings and Symptoms, Cardiovascular Diseases, Heart Diseases, Atrial Fibrillation, Arrhythmias, Cardiac, Pathologic Processes, Anticoagulants
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).
Interventions
DRUGfondaparinux
Comparison of different drugs
DRUGunfractionated heparin
Comparison of different drugs
DRUGVitamin-K-Antagonist
Comparison of different drugs
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Thrombus-negative and Thrombus-positive Participants With at Least One Systemic Thromboembolism | 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) | 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 | 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) | 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 | 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) | 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 | 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) | 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 Thrombus-negative and Thrombus-positive Participants (Par.) With at Least One Cerebral Neurologic Event | 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) | 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 Participants With a Thrombus in the Left Atrium (LA) or in the Left Atrial Appendage (LAA) at the Time of the Second TEE | At second TEE (at Day 28+/-4) | 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 | 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) | 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 | 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) | 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. |
| Number of Participants With Primary Successful Electrical Cardioversion (CV) in Sinus Rhythm | Day 1 until Day 3 | 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. |
Countries
France, Germany
Participant flow
Pre-assignment details
Participants (par.) were required to undergo transesophageal echocardiography (TEE) to guide cardioversion (CV). TEEs were recorded and archived to allow for later central adjudication and possible evaluation of details. At randomization (Day 1, immediately after TEE), par. were stratified to thrombus (clot)-positive and thrombus (clot)-negative.
Participants by arm
| Arm | Count |
|---|---|
| Fondaparinux For CN par., 7.5 mg fondaparinux was injected OD subcutaneously (for par. with BW 50-100 kg; for par. with BW \>100 kg, 10 mg fondaparinux was administered using a disposable prefilled syringe for the first 7-10 days after randomization, followed by 3 weeks of 2.5 mg fondaparinux OD (until Day 28+/-4). For CP par. with CrCl \>= 50 mL/min, 7.5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 10 mg fondaparinux was administered OD. For CP par. with CrCl 30 to \<50 mL/min, 5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW \>100 kg, 7.5 mg fondaparinux was injected for 28+/-4 days. If the second TEE showed thrombus disappearance, treatment continued until 7-10 days after the second TEE followed by 3 weeks of 2.5 mg fondaparinux OD (total treatment duration: 56+/-4 days). | 174 |
| UFH/VKA Both CN and CP participants received an initial i.v. bolus injection of 70 IU/kg (at least 5000 IU) UFH, followed by continuous infusion at an initial rate of 15 IU/kg/h (at least 1250 IU per h). The infusion dose was adjusted to maintain an activated partial thromboplastin aPTT at 1.5 to 2 times the reference control value. Infusion continued for at least 72 h. In parallel to UFH, treatment with VKA was started as soon as possible (preferably on Day 1). The dose of VKA was adjusted to reach a target INR of 2.0-3.0. UFH was continued until INR \>2.0. Total treatment duration: 28+/-4 days. For CP participants for whom the second TEE showed thrombus disappearance, VKA was continued during cardioversion and up to a total treatment duration of 56+/-4 days. | 170 |
| Total | 344 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 14 | 6 |
| Overall Study | Atrial Fibrillation (AF) Recurrence | 3 | 3 |
| Overall Study | Consent Withdrawn | 4 | 12 |
| Overall Study | Coronary Angiography Performed | 1 | 0 |
| Overall Study | CV Unsuccessful; Phenprocoumon Received | 1 | 0 |
| Overall Study | Death | 1 | 0 |
| Overall Study | International Normalized Ratio Too High | 0 | 1 |
| Overall Study | Investigator's Decision; New AF Episode | 0 | 1 |
| Overall Study | Nurse Unavailable in Participant's City | 1 | 0 |
| Overall Study | Participant Could Not Stay in Hospital | 0 | 1 |
| Overall Study | Participant Refused Hospital Consulation | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Primary Endpoint Component Occurred | 1 | 2 |
| Overall Study | Protocol Violation | 3 | 2 |
| Overall Study | Randomized; No Study Medication Received | 0 | 2 |
| Overall Study | Received Commercial Treatment | 1 | 0 |
| Overall Study | Recurrent Tachyarrhythmia | 1 | 1 |
| Overall Study | Recurrent Tachy-Arrhythmia Absoluta | 1 | 1 |
| Overall Study | Thrombus Persistant in Second TEE | 3 | 7 |
| Overall Study | Treatment Stopped by Mistake | 0 | 1 |
| Overall Study | Underlying Disease (Myocarditis) | 0 | 1 |
Baseline characteristics
| Characteristic | Fondaparinux | UFH/VKA | Total |
|---|---|---|---|
| Age Continuous | 68.24 Years STANDARD_DEVIATION 11.09 | 66.78 Years STANDARD_DEVIATION 11.93 | 67.52 Years STANDARD_DEVIATION 11.52 |
| Sex: Female, Male Female | 69 Participants | 60 Participants | 129 Participants |
| Sex: Female, Male Male | 105 Participants | 110 Participants | 215 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 68 / 174 | 70 / 170 |
| serious Total, serious adverse events | 30 / 174 | 26 / 170 |
Outcome results
Primary
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.
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
Population: Modified Intent-to-Treat (mITT) Population: all randomized participants receiving at least one dose of study medication and for whom any post-baseline value was available
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fondaparinux | 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 | 3 participants |
| UFH/VKA | 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 | 2 participants |
p-value: 195% CI: [-2, 3.1]Fisher Exact
Secondary
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.
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)
Population: mITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fondaparinux | Number of Participants Who Were Re-hospitalized | until the FU | 18 participants |
| Fondaparinux | Number of Participants Who Were Re-hospitalized | until 4 days after EOT | 14 participants |
| UFH/VKA | Number of Participants Who Were Re-hospitalized | until the FU | 11 participants |
| UFH/VKA | Number of Participants Who Were Re-hospitalized | until 4 days after EOT | 7 participants |
Secondary
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.
Time frame: At second TEE (at Day 28+/-4)
Population: mITT Population. Only clot-positive participants at the time of the first TEE were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fondaparinux | 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 | 3 participants |
| UFH/VKA | 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 | 7 participants |
Secondary
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.
Time frame: Day 1 until Day 3
Population: mITT Population. Only participants with data for primary successful electric cardioversion at the indicated timepoint were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fondaparinux | Number of Participants With Primary Successful Electrical Cardioversion (CV) in Sinus Rhythm | 137 participants |
| UFH/VKA | Number of Participants With Primary Successful Electrical Cardioversion (CV) in Sinus Rhythm | 133 participants |
Secondary
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).
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)
Population: mITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants (Par.) With at Least One Cerebral Neurologic Event | Thrombus-negative par. until 4 days after EOT | 0 participants |
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants (Par.) With at Least One Cerebral Neurologic Event | Thrombus-positive participants until the FU | 0 participants |
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants (Par.) With at Least One Cerebral Neurologic Event | Thrombus-positive par. until 4 days after EOT | 0 participants |
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants (Par.) With at Least One Cerebral Neurologic Event | Thrombus-negative participants until the FU | 1 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants (Par.) With at Least One Cerebral Neurologic Event | Thrombus-negative par. until 4 days after EOT | 1 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants (Par.) With at Least One Cerebral Neurologic Event | Thrombus-negative participants until the FU | 1 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants (Par.) With at Least One Cerebral Neurologic Event | Thrombus-positive par. until 4 days after EOT | 0 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants (Par.) With at Least One Cerebral Neurologic Event | Thrombus-positive participants until the FU | 0 participants |
Secondary
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).
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)
Population: mITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants Who Died From Any Cause | Thrombus-negative par. until 4 days after EOT | 1 participants |
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants Who Died From Any Cause | Thrombus-positive par. until 4 days after EOT | 0 participants |
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants Who Died From Any Cause | Thrombus-negative participants until the FU | 3 participants |
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants Who Died From Any Cause | Thrombus-positive participants until the FU | 0 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants Who Died From Any Cause | Thrombus-positive participants until the FU | 0 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants Who Died From Any Cause | Thrombus-negative par. until 4 days after EOT | 0 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants Who Died From Any Cause | Thrombus-negative participants until the FU | 0 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants Who Died From Any Cause | Thrombus-positive par. until 4 days after EOT | 0 participants |
Secondary
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).
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)
Population: mITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Major Bleeding Event | Thrombus-negative par. until 4 days after EOT | 3 participants |
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Major Bleeding Event | Thrombus-positive par. until 4 days after EOT | 0 participants |
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Major Bleeding Event | Thrombus-positive participants until the FU | 0 participants |
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Major Bleeding Event | Thrombus-negative participants until the FU | 4 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Major Bleeding Event | Thrombus-positive participants until the FU | 0 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Major Bleeding Event | Thrombus-negative par. until 4 days after EOT | 1 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Major Bleeding Event | Thrombus-positive par. until 4 days after EOT | 0 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Major Bleeding Event | Thrombus-negative participants until the FU | 1 participants |
Secondary
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.
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)
Population: mITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Minor Bleeding Event | Thrombus-negative par. until 4 days after EOT | 3 participants |
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Minor Bleeding Event | Thrombus-positive par. until 4 days after EOT | 0 participants |
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Minor Bleeding Event | Thrombus-negative participants until the FU | 3 participants |
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Minor Bleeding Event | Thrombus-positive participants until the FU | 1 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Minor Bleeding Event | Thrombus-positive participants until the FU | 0 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Minor Bleeding Event | Thrombus-negative par. until 4 days after EOT | 4 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Minor Bleeding Event | Thrombus-negative participants until the FU | 5 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Minor Bleeding Event | Thrombus-positive par. until 4 days after EOT | 0 participants |
Secondary
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).
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)
Population: mITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Systemic Thromboembolism | Thrombus-negative par. until 4 days after EOT | 0 participants |
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Systemic Thromboembolism | Thrombus-positive par. until 4 days after EOT | 0 participants |
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Systemic Thromboembolism | Thrombus-negative participants until the FU | 0 participants |
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Systemic Thromboembolism | Thrombus-positive participants until the FU | 0 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Systemic Thromboembolism | Thrombus-positive participants until the FU | 0 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Systemic Thromboembolism | Thrombus-negative par. until 4 days after EOT | 0 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Systemic Thromboembolism | Thrombus-negative participants until the FU | 0 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants With at Least One Systemic Thromboembolism | Thrombus-positive par. until 4 days after EOT | 0 participants |
Secondary
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.
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)
Population: mITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants With Conversion to Sinus Rhythm | Clot-negative par. until 4 days after EOT | 109 participants |
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants With Conversion to Sinus Rhythm | Clot-positive par. until 4 days after EOT | 5 participants |
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants With Conversion to Sinus Rhythm | Clot-negative participants until the FU | 105 participants |
| Fondaparinux | Number of Thrombus-negative and Thrombus-positive Participants With Conversion to Sinus Rhythm | Clot-positive participants until the FU | 4 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants With Conversion to Sinus Rhythm | Clot-positive participants until the FU | 5 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants With Conversion to Sinus Rhythm | Clot-negative par. until 4 days after EOT | 115 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants With Conversion to Sinus Rhythm | Clot-negative participants until the FU | 106 participants |
| UFH/VKA | Number of Thrombus-negative and Thrombus-positive Participants With Conversion to Sinus Rhythm | Clot-positive par. until 4 days after EOT | 4 participants |