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

May 28, 2009
September 20, 2012
August 2009
September 2011   (final data collection date for primary outcome measure)
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.
  • Evidence of clinically definite new neurologic disorders caused by cerebrovascular embolisation confirmed by objective standard of care diagnostic procedures, like for example megnetic resonance imaging or cerebral computed tomography [ Time Frame: within the whole treatment period, i.e., from randomisation up to 4 days after the last administration of study drug (Day 32 plus or minus 4 days or Day 60 plus or minus 4 days) ] [ Designated as safety issue: No ]
  • Evidence of clinically definite arterial thromboembolic events confirmed by objective standard of care diagnostic procedures, like for example angiography [ Time Frame: within the whole treatment period, i.e., from randomisation up to 4 days after the last administration of study drug (Day 32 plus or minus 4 days or Day 60 plus or minus 4 days) ] [ Designated as safety issue: No ]
  • Death from any cause [ Time Frame: within the whole treatment period, i.e., from randomisation up to 4 days after the last administration of study drug (Day 32 plus or minus 4 days or Day 60 plus or minus 4 days) ] [ Designated as safety issue: No ]
  • Major bleeding events which are clinically overt; laboratory measures are part of the definition of major bleeding events [ Time Frame: within the whole treatment period, i.e., from randomisation up to 4 days after the last administration of study drug (Day 32 plus or minus 4 days or Day 60 plus or minus 4 days) ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00911300 on ClinicalTrials.gov Archive Site
  • 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.
  • Presence or absence of a thrombus in the left atrium or in the left atrial appendage at second TEE [ Time Frame: Day 28 plus or minus 4 days ] [ Designated as safety issue: No ]
  • Re-hospitalisation of patients [ Time Frame: within the period between discharge after the initial hospitalisation until the end of the treatment period, i.e., until 4 days after the last administration of study drug (Day 32 plus or minus 4 days or Day 60 plus or minus 4 days) ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Evaluation of Fondaparinux in Patients With a Heart Rhythm Disturbance Who Undergo Restoration of Normal Heart Rhythm
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

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).

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Fibrillation, Atrial
  • Drug: fondaparinux
    Comparison of different drugs
  • Drug: unfractionated heparin
    Comparison of different drugs
  • Drug: Vitamin-K-Antagonist
    Comparison of different drugs
  • Active Comparator: Arm 1: fondaparinux
    Intervention: Drug: fondaparinux
  • Active Comparator: Arm 2: unfractionated heparin + Vitamin-K-Antagonist
    Interventions:
    • Drug: unfractionated heparin
    • Drug: Vitamin-K-Antagonist
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
349
September 2011
September 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France,   Germany
 
NCT00911300
111418
Not Provided
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
September 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP