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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00911300
First received: May 28, 2009
Last updated: September 20, 2012
Last verified: September 2012
  Purpose

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 Intervention Phase
Fibrillation, Atrial
Drug: fondaparinux
Drug: unfractionated heparin
Drug: Vitamin-K-Antagonist
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants With at Least One Event of Cerebral Neurologic Event, Systemic Thromboembolism, Death From Any Cause, and/or Major Bleeding Until the End of Treatment (EOT) Plus 4 Days [ 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 ] [ Designated as safety issue: No ]
    Cerebral neurologic events are defined as any new neurologic disorders caused by cerebrovascular embolization, e.g., Transient Ischemic Attack (TIA), cerebral infarction. The cerebrovascular origin of the event has to be confirmed by objective procedures. Systemic thromboembolism comprises any arterial thromboembolic event (e.g., peripheral vascular embolism, mesenteric infarct, or myocardial infarction). All cerebral neurologic events were adjudicated by a Central Adjudication Committee (CAC), members of which were unaware of the participants' treatment assignment.


Secondary Outcome Measures:
  • Number of Thrombus-negative and Thrombus-positive Participants (Par.) With at Least One Cerebral Neurologic Event [ 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) ] [ Designated as safety issue: No ]
    Cerebral neurologic events are defined as any new neurologic disorders caused by cerebrovascular embolisation, e.g., TIA, cerebral infarction. All cerebral neurologic events were adjudicated by a CAC, members of which were unaware of the participants' treatment assignment.The cerebrovascular origin of the event was confirmed by objective procedures. A thrombus or blood clot is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system (i.e., clotting factors).

  • Number of Thrombus-negative and Thrombus-positive Participants With at Least One Systemic Thromboembolism [ 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) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    Minor bleeding is defined as clinically overt bleeding events that do not meet the criteria for major or clinically relevant non-major bleeding. All episodes of bleeding were adjudicated by an independent CAC, the members of which were unaware of the participants' treatment assignment.

  • Number of Participants With Primary Successful Electrical Cardioversion (CV) in Sinus Rhythm [ Time Frame: Day 1 until Day 3 ] [ Designated as safety issue: No ]
    CV may be performed electively to restore sinus rhythm in patients with persistent AF. The primary successful electric CV was assessed by a 12- lead electrocardiogram (ECG) directly after the CV. Results of the last cardioversion were used in cases for which more than one CV was performed.

  • Number of Participants With a Thrombus in the Left Atrium (LA) or in the Left Atrial Appendage (LAA) at the Time of the Second TEE [ Time Frame: At second TEE (at Day 28+/-4) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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.


Enrollment: 349
Study Start Date: August 2009
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients aged at least 18 years with atrial fibrillation (AF) meeting at least one of the following criteria (a, b, c): a. Acute clinical symptoms (like palpitations, chest pain, dyspnea, fatigue, lightheadedness, or syncope) for at least 48 hours and AF on baseline ECG b. Newly discovered AF persisting for >=7 days c. Recurrent AF persisting for >=7 days

Exclusion Criteria:

  • No documented sinus rhythm on ECG for more than 1 year
  • Acute neurological deficits (TIA, stroke, intracranial bleeding), or known disease which may cause neurological deficits (e.g., multiple sclerosis, seizure disorder)
  • Treatment with antithrombotic agents, including low-dose anticoagulation, for more than 48 hours prior to randomisation
  • Treatment with oral NSAIDs or ASA at doses greater than 325 mg per day for more than 72 hours prior to randomisation
  • Anticoagulant therapy required or likely to be required during the study period
  • Treatment with ASA at a dose greater than 325 mg per day or oral NSAIDs (at any dose) required or likely to be required during the study period
  • Treatment with two or more antiplatelet agents (e.g. clopidogrel and ASA) at any dose at the same time (i.e., within 24 hours)
  • Known hypersensitivity to UFH, VKA, or Fondaparinux or one of these drugs' excipients
  • Active, clinically significant bleeding or clinically significant bleeding within the past month
  • Major surgery within the previous three months
  • Uncontrolled arterial hypertension (persistent systolic blood pressure over 180 mm Hg or diastolic blood pressure over 110 mm Hg)
  • Bacterial endocarditis
  • Calculated creatinine clearance < 30 mL/min
  • Body weight < 50 kg
  • Planned surgery or intervention within the next 65 days
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00911300

Locations
France
GSK Investigational Site
Albi, France, 81000
GSK Investigational Site
Antony cedex, France, 92166
GSK Investigational Site
Brest Cedex, France, 29609
GSK Investigational Site
Créteil, France, 94000
GSK Investigational Site
Evecquemont, France, 78740
GSK Investigational Site
Montpellier Cedex 5, France, 34295
GSK Investigational Site
Paris cedex 12, France, 75571
GSK Investigational Site
Paris cedex 13, France, 75651
GSK Investigational Site
Pau, France, 64046
GSK Investigational Site
Pessac cedex, France, 33604
GSK Investigational Site
Poitiers cedex, France, 86021
GSK Investigational Site
Rennes Cedex 9, France, 35033
GSK Investigational Site
Toulouse Cedex 09, France, 31059
GSK Investigational Site
Toulouse cedex 3, France, 31076
Germany
GSK Investigational Site
Freiburg, Baden-Wuerttemberg, Germany, 79106
GSK Investigational Site
Aschaffenburg, Bayern, Germany, 63739
GSK Investigational Site
Bad Toelz, Bayern, Germany, 83646
GSK Investigational Site
Simbach a. Inn, Bayern, Germany, 84359
GSK Investigational Site
Potsdam, Brandenburg, Germany, 14467
GSK Investigational Site
Frankfurt, Hessen, Germany, 60488
GSK Investigational Site
Kassel, Hessen, Germany, 34121
GSK Investigational Site
Kassel, Hessen, Germany, 34125
GSK Investigational Site
Hagenow, Mecklenburg-Vorpommern, Germany, 19230
GSK Investigational Site
Bielefeld, Nordrhein-Westfalen, Germany, 33604
GSK Investigational Site
Bonn, Nordrhein-Westfalen, Germany, 53127
GSK Investigational Site
Bonn, Nordrhein-Westfalen, Germany, 53115
GSK Investigational Site
Duisburg-Huckingen, Nordrhein-Westfalen, Germany, 47259
GSK Investigational Site
Unna, Nordrhein-Westfalen, Germany, 59423
GSK Investigational Site
Wesel, Nordrhein-Westfalen, Germany, 46483
GSK Investigational Site
Magdeburg, Sachsen-Anhalt, Germany, 39120
GSK Investigational Site
Pirna, Sachsen, Germany, 01796
GSK Investigational Site
Berlin, Germany, 13353
GSK Investigational Site
Berlin, Germany, 10249
GSK Investigational Site
Berlin, Germany, 10405
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00911300     History of Changes
Other Study ID Numbers: 111418
Study First Received: May 28, 2009
Results First Received: August 2, 2012
Last Updated: September 20, 2012
Health Authority: Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
France: Agence Française de Sécurité Sanitaire des Produits de Santé

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
Arrhythmias, Cardiac
Cardiovascular Diseases
Heart Diseases
Pathologic Processes
Calcium heparin
Fondaparinux
Heparin
PENTA
Vitamin K
Vitamins
Anticoagulants
Antifibrinolytic Agents
Cardiovascular Agents
Coagulants
Fibrin Modulating Agents
Fibrinolytic Agents
Growth Substances
Hematologic Agents
Hemostatics
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014