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

Fibrillation, Atrial Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00911300
• Other study ID #: 111418
• Status: Completed
• Phase: Phase 2
• First received: May 28, 2009
• Last updated: September 20, 2012
• Start date: August 2009
• Est. completion date: September 2011

Study information

• Verified date: September 2012
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Bundesinstitut für Arzneimittel und MedizinprodukteFrance: Agence Française de Sécurité Sanitaire des Produits de Santé
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 349
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Atrial Fibrillation
• Fibrillation, Atrial

Intervention

Drug:
• fondaparinux
Comparison of different drugs
• unfractionated heparin
Comparison of different drugs
• Vitamin-K-Antagonist
Comparison of different drugs

Locations

Country	Name	City	State
France	GSK Investigational Site	Albi
France	GSK Investigational Site	Antony cedex
France	GSK Investigational Site	Brest Cedex
France	GSK Investigational Site	Créteil
France	GSK Investigational Site	Evecquemont
France	GSK Investigational Site	Montpellier Cedex 5
France	GSK Investigational Site	Paris cedex 12
France	GSK Investigational Site	Paris cedex 13
France	GSK Investigational Site	Pau
France	GSK Investigational Site	Pessac cedex
France	GSK Investigational Site	Poitiers cedex
France	GSK Investigational Site	Rennes Cedex 9
France	GSK Investigational Site	Toulouse Cedex 09
France	GSK Investigational Site	Toulouse cedex 3
Germany	GSK Investigational Site	Aschaffenburg	Bayern
Germany	GSK Investigational Site	Bad Toelz	Bayern
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Bielefeld	Nordrhein-Westfalen
Germany	GSK Investigational Site	Bonn	Nordrhein-Westfalen
Germany	GSK Investigational Site	Bonn	Nordrhein-Westfalen
Germany	GSK Investigational Site	Duisburg-Huckingen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Freiburg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Hagenow	Mecklenburg-Vorpommern
Germany	GSK Investigational Site	Kassel	Hessen
Germany	GSK Investigational Site	Kassel	Hessen
Germany	GSK Investigational Site	Magdeburg	Sachsen-Anhalt
Germany	GSK Investigational Site	Pirna	Sachsen
Germany	GSK Investigational Site	Potsdam	Brandenburg
Germany	GSK Investigational Site	Simbach a. Inn	Bayern
Germany	GSK Investigational Site	Unna	Nordrhein-Westfalen
Germany	GSK Investigational Site	Wesel	Nordrhein-Westfalen

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

France,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	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	No
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).	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)	No
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).	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)	No
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).	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)	No
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).	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)	No
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.	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)	No
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.	Day 1 until Day 3	No
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.	At second TEE (at Day 28+/-4)	No
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.	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)	No
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.	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)	No