Evaluation of Fondaparinux in Patients With a Heart Rhythm Disturbance Who Undergo Restoration of Normal Heart Rhythm

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00911300
• Collaborator: (none)
• Enrollment: 349
• Locations: 34
• Arms: 2
• Duration (Months): 25
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.4

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Fibrillation, Atrial	Drug: fondaparinux; Drug: unfractionated heparin; Drug: Vitamin-K-Antagonist	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 349 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• 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 Start Date: Aug 1, 2009
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1: fondaparinux	Drug: fondaparinux; Comparison of different drugs
Active Comparator: Arm 2: unfractionated heparin + Vitamin-K-Antagonist	Drug: unfractionated heparin; Comparison of different drugs; Drug: Vitamin-K-Antagonist; Comparison of different drugs

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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).

2. 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).

3. 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).

4. 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).

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Albi		France	81000
2	GSK Investigational Site	Antony cedex		France	92166
3	GSK Investigational Site	Brest Cedex		France	29609
4	GSK Investigational Site	Créteil		France	94000
5	GSK Investigational Site	Evecquemont		France	78740
6	GSK Investigational Site	Montpellier Cedex 5		France	34295
7	GSK Investigational Site	Paris cedex 12		France	75571
8	GSK Investigational Site	Paris cedex 13		France	75651
9	GSK Investigational Site	Pau		France	64046
10	GSK Investigational Site	Pessac cedex		France	33604
11	GSK Investigational Site	Poitiers cedex		France	86021
12	GSK Investigational Site	Rennes Cedex 9		France	35033
13	GSK Investigational Site	Toulouse Cedex 09		France	31059
14	GSK Investigational Site	Toulouse cedex 3		France	31076
15	GSK Investigational Site	Freiburg	Baden-Wuerttemberg	Germany	79106
16	GSK Investigational Site	Aschaffenburg	Bayern	Germany	63739
17	GSK Investigational Site	Bad Toelz	Bayern	Germany	83646
18	GSK Investigational Site	Simbach a. Inn	Bayern	Germany	84359
19	GSK Investigational Site	Potsdam	Brandenburg	Germany	14467
20	GSK Investigational Site	Frankfurt	Hessen	Germany	60488
21	GSK Investigational Site	Kassel	Hessen	Germany	34121
22	GSK Investigational Site	Kassel	Hessen	Germany	34125
23	GSK Investigational Site	Hagenow	Mecklenburg-Vorpommern	Germany	19230
24	GSK Investigational Site	Bielefeld	Nordrhein-Westfalen	Germany	33604
25	GSK Investigational Site	Bonn	Nordrhein-Westfalen	Germany	53115
26	GSK Investigational Site	Bonn	Nordrhein-Westfalen	Germany	53127
27	GSK Investigational Site	Duisburg-Huckingen	Nordrhein-Westfalen	Germany	47259
28	GSK Investigational Site	Unna	Nordrhein-Westfalen	Germany	59423
29	GSK Investigational Site	Wesel	Nordrhein-Westfalen	Germany	46483
30	GSK Investigational Site	Magdeburg	Sachsen-Anhalt	Germany	39120
31	GSK Investigational Site	Pirna	Sachsen	Germany	01796
32	GSK Investigational Site	Berlin		Germany	10249
33	GSK Investigational Site	Berlin		Germany	10405
34	GSK Investigational Site	Berlin		Germany	13353

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00911300
• Other Study ID Numbers: 111418
• First Posted: Jun 1, 2009
• Last Update Posted: Oct 1, 2012
• Last Verified: Sep 1, 2012

• Keywords provided by GlaxoSmithKline: Cardioversion, Electric; Pathological Conditions, Sings and Symptoms; Cardiovascular Diseases; Heart Diseases; Atrial Fibrillation; Arrhythmias, Cardiac; Pathologic Processes; Anticoagulants
• Additional relevant MeSH terms: Atrial Fibrillation; Vitamin K; Heparin; Calcium heparin; PENTA; Fondaparinux

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Fondaparinux	Unfractioned Heparin (UFH)/Vitamin K Antagonist (VKA)
Arm/Group Description	For clot-negative (CN) participants (par.), 7.5 milligrams (mg) fondaparinux was injected once daily (OD) subcutaneously (for par. with body weight [BW] 50-100 kilograms [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 clot-positive (CP) par. with creatinine clearance (CrCl) >= 50 milliliters (mL)/minute (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).	Both CN and CP participants received an initial intravenous (i.v.) bolus injection of 70 international units (IU)/kg (at least 5000 IU) UFH, followed by continuous infusion at an initial rate of 15 IU/kg/hour (h) (at least 1250 IU per hour). The infusion dose was adjusted to maintain an activated partial thromboplastin time (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 international normalized ratio (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.
Period Title: Overall Study
STARTED	175	174
COMPLETED	140	131
NOT COMPLETED	35	43

Baseline Characteristics

Arm/Group Title	Fondaparinux	UFH/VKA	Total
Arm/Group Description	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).	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.	Total of all reporting groups
Overall Participants	174	170	344
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	68.24 (11.09)	66.78 (11.93)	67.52 (11.52)
Sex: Female, Male (Count of Participants)
Female	69 39.7%	60 35.3%	129 37.5%
Male	105 60.3%	110 64.7%	215 62.5%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Fondaparinux	UFH/VKA
Arm/Group Description	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).	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 &amp;gt;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.
Measure Participants	174	170
Number [participants]	3 1.7%	2 1.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fondaparinux, UFH/VKA
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Percentage of participants
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -2.0 to 3.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value is the absolute percent difference between Fondaparinux and UFH/VKA.

2. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Fondaparinux	UFH/VKA
Arm/Group Description	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).	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 &amp;gt;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.
Measure Participants	174	170
Thrombus-negative par. until 4 days after EOT	0 0%	1 0.6%
Thrombus-positive par. until 4 days after EOT	0 0%	0 0%
Thrombus-negative participants until the FU	1 0.6%	1 0.6%
Thrombus-positive participants until the FU	0 0%	0 0%

3. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Fondaparinux	UFH/VKA
Arm/Group Description	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).	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 &amp;gt;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.
Measure Participants	174	170
Thrombus-negative par. until 4 days after EOT	0 0%	0 0%
Thrombus-positive par. until 4 days after EOT	0 0%	0 0%
Thrombus-negative participants until the FU	0 0%	0 0%
Thrombus-positive participants until the FU	0 0%	0 0%

4. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Fondaparinux	UFH/VKA
Arm/Group Description	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).	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 &amp;gt;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.
Measure Participants	174	170
Thrombus-negative par. until 4 days after EOT	1 0.6%	0 0%
Thrombus-positive par. until 4 days after EOT	0 0%	0 0%
Thrombus-negative participants until the FU	3 1.7%	0 0%
Thrombus-positive participants until the FU	0 0%	0 0%

5. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Fondaparinux	UFH/VKA
Arm/Group Description	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).	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 &amp;gt;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.
Measure Participants	174	170
Thrombus-negative par. until 4 days after EOT	3 1.7%	1 0.6%
Thrombus-positive par. until 4 days after EOT	0 0%	0 0%
Thrombus-negative participants until the FU	4 2.3%	1 0.6%
Thrombus-positive participants until the FU	0 0%	0 0%

6. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Fondaparinux	UFH/VKA
Arm/Group Description	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).	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 &amp;gt;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.
Measure Participants	174	170
Thrombus-negative par. until 4 days after EOT	3 1.7%	4 2.4%
Thrombus-positive par. until 4 days after EOT	0 0%	0 0%
Thrombus-negative participants until the FU	3 1.7%	5 2.9%
Thrombus-positive participants until the FU	1 0.6%	0 0%

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

mITT Population. Only participants with data for primary successful electric cardioversion at the indicated timepoint were analyzed.

Arm/Group Title	Fondaparinux	UFH/VKA
Arm/Group Description	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).	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 &amp;gt;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.
Measure Participants	151	148
Number [participants]	137 78.7%	133 78.2%

8. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

mITT Population. Only clot-positive participants at the time of the first TEE were analyzed.

Arm/Group Title	Fondaparinux	UFH/VKA
Arm/Group Description	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).	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 &amp;gt;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.
Measure Participants	14	14
Number [participants]	3 1.7%	7 4.1%

9. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Fondaparinux	UFH/VKA
Arm/Group Description	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).	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 &gt;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.
Measure Participants	174	170
Clot-negative par. until 4 days after EOT	109 62.6%	115 67.6%
Clot-positive par. until 4 days after EOT	5 2.9%	4 2.4%
Clot-negative participants until the FU	105 60.3%	106 62.4%
Clot-positive participants until the FU	4 2.3%	5 2.9%

10. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Fondaparinux	UFH/VKA
Arm/Group Description	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).	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 &gt;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.
Measure Participants	174	170
until 4 days after EOT	14 8%	7 4.1%
until the FU	18 10.3%	11 6.5%

Adverse Events

Time Frame	Participants were analyzed for the period from randomization up to the last administration of study treatment plus four days (up to Day 56+/-4 days).
Adverse Event Reporting Description	Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Population, comprised of all participants included in the study, who had any post-baseline value, and who received at least one dose of study medication.
Arm/Group Title	Fondaparinux		UFH/VKA
Arm/Group Description	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).		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.
All Cause Mortality
	Fondaparinux		UFH/VKA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fondaparinux		UFH/VKA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/174 (17.2%)		26/170 (15.3%)
Cardiac disorders
Atrial fibrillation	12/174 (6.9%)		5/170 (2.9%)
Cardiac failure	4/174 (2.3%)		3/170 (1.8%)
Angina pectoris	1/174 (0.6%)		1/170 (0.6%)
Atrial flutter	0/174 (0%)		2/170 (1.2%)
Cardiac failure congestive	1/174 (0.6%)		1/170 (0.6%)
Tachyarrhythmia	0/174 (0%)		2/170 (1.2%)
Arrhythmia supraventricular	0/174 (0%)		1/170 (0.6%)
Atrioventricular block complete	1/174 (0.6%)		0/170 (0%)
Cardiac valve disease	1/174 (0.6%)		0/170 (0%)
Coronary artery disease	1/174 (0.6%)		0/170 (0%)
Ischemic cardiomyopathy	0/174 (0%)		1/170 (0.6%)
Mitral valve incompetence	1/174 (0.6%)		0/170 (0%)
Sinoatrial block	0/174 (0%)		1/170 (0.6%)
Gastrointestinal disorders
Gastrointestinal hemorrhage	1/174 (0.6%)		1/170 (0.6%)
Colonic polyp	0/174 (0%)		1/170 (0.6%)
Diarrhea	1/174 (0.6%)		0/170 (0%)
Erosive esophagitis	0/174 (0%)		1/170 (0.6%)
Vomiting	1/174 (0.6%)		0/170 (0%)
General disorders
Death	1/174 (0.6%)		0/170 (0%)
Infections and infestations
Gastroenteritis	1/174 (0.6%)		0/170 (0%)
Staphylococcal sepsis	0/174 (0%)		1/170 (0.6%)
Injury, poisoning and procedural complications
Fall	0/174 (0%)		1/170 (0.6%)
Metabolism and nutrition disorders
Hypokalemia	1/174 (0.6%)		0/170 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/174 (0%)		1/170 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bronchial carcinoma	1/174 (0.6%)		0/170 (0%)
Colon cancer	1/174 (0.6%)		0/170 (0%)
Neoplasm skin	1/174 (0.6%)		0/170 (0%)
Rectal cancer	0/174 (0%)		1/170 (0.6%)
Nervous system disorders
Cerebrovascular accident	1/174 (0.6%)		1/170 (0.6%)
Syncope	1/174 (0.6%)		1/170 (0.6%)
Cerebral infarction	1/174 (0.6%)		0/170 (0%)
Renal and urinary disorders
Renal failure acute	1/174 (0.6%)		1/170 (0.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/174 (0.6%)		2/170 (1.2%)
Pulmonary edema	1/174 (0.6%)		1/170 (0.6%)
Skin and subcutaneous tissue disorders
Skin necrosis	0/174 (0%)		1/170 (0.6%)
Vascular disorders
Hematoma	1/174 (0.6%)		2/170 (1.2%)
Hypertensive crisis	1/174 (0.6%)		0/170 (0%)
Other (Not Including Serious) Adverse Events
	Fondaparinux		UFH/VKA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	68/174 (39.1%)		70/170 (41.2%)
Blood and lymphatic system disorders
Anemia	1/174 (0.6%)		0/170 (0%)
Cardiac disorders
Atrial fibrillation	13/174 (7.5%)		11/170 (6.5%)
Bradycardia	2/174 (1.1%)		2/170 (1.2%)
Angina pectoris	0/174 (0%)		1/170 (0.6%)
Atrial flutter	0/174 (0%)		1/170 (0.6%)
Atrioventricular block first degree	0/174 (0%)		1/170 (0.6%)
Cardiac failure	1/174 (0.6%)		0/170 (0%)
Mitral valve incompetence	1/174 (0.6%)		0/170 (0%)
Palpitations	0/174 (0%)		1/170 (0.6%)
Sinus bradycardia	0/174 (0%)		1/170 (0.6%)
Supraventricular extrasystoles	1/174 (0.6%)		0/170 (0%)
Tricuspid valve incompetence	1/174 (0.6%)		0/170 (0%)
Ventricular tachycardia	1/174 (0.6%)		0/170 (0%)
Ear and labyrinth disorders
Vertigo	5/174 (2.9%)		3/170 (1.8%)
Tinnitus	0/174 (0%)		1/170 (0.6%)
Endocrine disorders
Hyperthyroidism	0/174 (0%)		1/170 (0.6%)
Hypothyroidism	0/174 (0%)		1/170 (0.6%)
Eye disorders
Vision blurred	0/174 (0%)		1/170 (0.6%)
Gastrointestinal disorders
Diarrhea	3/174 (1.7%)		5/170 (2.9%)
Vomiting	6/174 (3.4%)		1/170 (0.6%)
Constipation	3/174 (1.7%)		3/170 (1.8%)
Nausea	4/174 (2.3%)		2/170 (1.2%)
Abdominal pain upper	0/174 (0%)		2/170 (1.2%)
Abdominal discomfort	0/174 (0%)		1/170 (0.6%)
Abdominal pain	1/174 (0.6%)		0/170 (0%)
Dry mouth	1/174 (0.6%)		0/170 (0%)
Dysphagia	0/174 (0%)		1/170 (0.6%)
Gastric disorder	1/174 (0.6%)		0/170 (0%)
Gastrointestinal pain	0/174 (0%)		1/170 (0.6%)
Intestinal hemorrhage	1/174 (0.6%)		0/170 (0%)
Toothache	0/174 (0%)		1/170 (0.6%)
General disorders
Edema	4/174 (2.3%)		3/170 (1.8%)
Chest pain	4/174 (2.3%)		2/170 (1.2%)
Edema peripheral	1/174 (0.6%)		3/170 (1.8%)
Chest discomfort	0/174 (0%)		3/170 (1.8%)
Asthenia	1/174 (0.6%)		0/170 (0%)
Fatigue	1/174 (0.6%)		0/170 (0%)
Vessel puncture site hematoma	1/174 (0.6%)		0/170 (0%)
Infections and infestations
Urinary tract infection	3/174 (1.7%)		3/170 (1.8%)
Nasopharyngitis	1/174 (0.6%)		2/170 (1.2%)
Lung infection	1/174 (0.6%)		1/170 (0.6%)
Bronchitis	0/174 (0%)		1/170 (0.6%)
Cystitis	1/174 (0.6%)		0/170 (0%)
Gastroenteritis norovirus	0/174 (0%)		1/170 (0.6%)
Infection	1/174 (0.6%)		0/170 (0%)
Onychomycosis	0/174 (0%)		1/170 (0.6%)
Paronychia	0/174 (0%)		1/170 (0.6%)
Sebaceous gland infection	1/174 (0.6%)		0/170 (0%)
Varicella	0/174 (0%)		1/170 (0.6%)
Injury, poisoning and procedural complications
Contusion	2/174 (1.1%)		0/170 (0%)
Ankle fracture	1/174 (0.6%)		0/170 (0%)
Joint sprain	1/174 (0.6%)		0/170 (0%)
Wound	1/174 (0.6%)		0/170 (0%)
Investigations
C-reactive protein increased	0/174 (0%)		2/170 (1.2%)
Blood creatinine increased	0/174 (0%)		1/170 (0.6%)
Blood potassium decreased	0/174 (0%)		1/170 (0.6%)
International normalised ratio decreased	0/174 (0%)		1/170 (0.6%)
International normalized ratio increased	0/174 (0%)		1/170 (0.6%)
Weight decreased	1/174 (0.6%)		0/170 (0%)
Metabolism and nutrition disorders
Hypokalemia	4/174 (2.3%)		2/170 (1.2%)
Gout	0/174 (0%)		2/170 (1.2%)
Hyperkalemia	2/174 (1.1%)		0/170 (0%)
Appetite disorder	1/174 (0.6%)		0/170 (0%)
Hypercholesterolaemia	0/174 (0%)		1/170 (0.6%)
Magnesium deficiency	0/174 (0%)		1/170 (0.6%)
Musculoskeletal and connective tissue disorders
Back pain	0/174 (0%)		2/170 (1.2%)
Musculoskeletal pain	1/174 (0.6%)		1/170 (0.6%)
Arthralgia	1/174 (0.6%)		0/170 (0%)
Myalgia	1/174 (0.6%)		0/170 (0%)
Osteoarthritis	0/174 (0%)		1/170 (0.6%)
Pain in extremity	1/174 (0.6%)		0/170 (0%)
Sensation of heaviness	1/174 (0.6%)		0/170 (0%)
Spinal disorder	1/174 (0.6%)		0/170 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostatic adenoma	0/174 (0%)		1/170 (0.6%)
Nervous system disorders
Headache	7/174 (4%)		0/170 (0%)
Dizziness	1/174 (0.6%)		2/170 (1.2%)
Syncope	0/174 (0%)		2/170 (1.2%)
Paraesthesia	1/174 (0.6%)		0/170 (0%)
Restless legs syndrome	0/174 (0%)		1/170 (0.6%)
Psychiatric disorders
Sleep disorder	2/174 (1.1%)		4/170 (2.4%)
Insomnia	1/174 (0.6%)		2/170 (1.2%)
Disorientation	0/174 (0%)		1/170 (0.6%)
Nightmare	0/174 (0%)		1/170 (0.6%)
Transient psychosis	0/174 (0%)		1/170 (0.6%)
Renal and urinary disorders
Renal cyst	1/174 (0.6%)		0/170 (0%)
Renal failure	1/174 (0.6%)		0/170 (0%)
Renal impairment	1/174 (0.6%)		0/170 (0%)
Reproductive system and breast disorders
Menstruation irregular	1/174 (0.6%)		0/170 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/174 (0.6%)		4/170 (2.4%)
Cough	3/174 (1.7%)		1/170 (0.6%)
Epistaxis	2/174 (1.1%)		2/170 (1.2%)
Oropharyngeal pain	1/174 (0.6%)		2/170 (1.2%)
Hemoptysis	1/174 (0.6%)		1/170 (0.6%)
Pleural effusion	2/174 (1.1%)		0/170 (0%)
Bronchial disorder	1/174 (0.6%)		0/170 (0%)
Pulmonary hypertension	1/174 (0.6%)		0/170 (0%)
Rhinalgia	1/174 (0.6%)		0/170 (0%)
Skin and subcutaneous tissue disorders
Rash	2/174 (1.1%)		2/170 (1.2%)
Pruritus	3/174 (1.7%)		0/170 (0%)
Alopecia	1/174 (0.6%)		0/170 (0%)
Dermatitis allergic	0/174 (0%)		1/170 (0.6%)
Drug eruption	1/174 (0.6%)		0/170 (0%)
Hyperhidrosis	1/174 (0.6%)		0/170 (0%)
Hyperkeratosis	0/174 (0%)		1/170 (0.6%)
Psoriasis	0/174 (0%)		1/170 (0.6%)
Skin hemorrhage	0/174 (0%)		1/170 (0.6%)
Surgical and medical procedures
Skin operation	1/174 (0.6%)		0/170 (0%)
Tooth extraction	0/174 (0%)		1/170 (0.6%)
Vascular disorders
Hypertension	4/174 (2.3%)		3/170 (1.8%)
Hematoma	3/174 (1.7%)		2/170 (1.2%)
Hypotension	4/174 (2.3%)		0/170 (0%)
Hypertensive crisis	0/174 (0%)		2/170 (1.2%)
Phlebitis	2/174 (1.1%)		0/170 (0%)
Circulatory collapse	0/174 (0%)		1/170 (0.6%)
Thrombophlebitis	1/174 (0.6%)		0/170 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.