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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
History of Changes
Results First Received: August 2, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Condition: Fibrillation, Atrial
Interventions: Drug: fondaparinux
Drug: unfractionated heparin
Drug: Vitamin-K-Antagonist

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
Fondaparinux 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).
Unfractioned Heparin (UFH)/Vitamin K Antagonist (VKA) 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.

Participant Flow:   Overall Study
    Fondaparinux     Unfractioned Heparin (UFH)/Vitamin K Antagonist (VKA)  
STARTED     175     174  
COMPLETED     140     131  
NOT COMPLETED     35     43  
Primary Endpoint Component Occurred                 1                 2  
Death                 1                 0  
Thrombus Persistant in Second TEE                 3                 7  
Adverse Event                 14                 6  
Protocol Violation                 3                 2  
Consent Withdrawn                 4                 12  
Coronary Angiography Performed                 1                 0  
Atrial Fibrillation (AF) Recurrence                 3                 3  
Received Commercial Treatment                 1                 0  
Recurrent Tachyarrhythmia                 1                 1  
Recurrent Tachy-Arrhythmia Absoluta                 1                 1  
Nurse Unavailable in Participant's City                 1                 0  
CV Unsuccessful; Phenprocoumon Received                 1                 0  
Participant Could Not Stay in Hospital                 0                 1  
Investigator's Decision; New AF Episode                 0                 1  
International Normalized Ratio Too High                 0                 1  
Participant Refused Hospital Consulation                 0                 1  
Underlying Disease (Myocarditis)                 0                 1  
Physician Decision                 0                 1  
Treatment Stopped by Mistake                 0                 1  
Randomized; No Study Medication Received                 0                 2  



  Baseline Characteristics
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Reporting Groups
  Description
Fondaparinux For CN par., 7.5 mg fondaparinux was injected OD subcutaneously (for par. with BW 50-100 kg; for par. with BW >100 kg, 10 mg fondaparinux was administered using a disposable prefilled syringe for the first 7-10 days after randomization, followed by 3 weeks of 2.5 mg fondaparinux OD (until Day 28+/-4). For CP par. with CrCl >= 50 mL/min, 7.5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW >100 kg, 10 mg fondaparinux was administered OD. For CP par. with CrCl 30 to <50 mL/min, 5 mg fondaparinux was injected OD (for par. with BW 50-100 kg); for par. with BW >100 kg, 7.5 mg fondaparinux was injected for 28+/-4 days. If the second TEE showed thrombus disappearance, treatment continued until 7-10 days after the second TEE followed by 3 weeks of 2.5 mg fondaparinux OD (total treatment duration: 56+/-4 days).
UFH/VKA Both CN and CP participants received an initial i.v. bolus injection of 70 IU/kg (at least 5000 IU) UFH, followed by continuous infusion at an initial rate of 15 IU/kg/h (at least 1250 IU per h). The infusion dose was adjusted to maintain an activated partial thromboplastin aPTT at 1.5 to 2 times the reference control value. Infusion continued for at least 72 h. In parallel to UFH, treatment with VKA was started as soon as possible (preferably on Day 1). The dose of VKA was adjusted to reach a target INR of 2.0-3.0. UFH was continued until INR >2.0. Total treatment duration: 28+/-4 days. For CP participants for whom the second TEE showed thrombus disappearance, VKA was continued during cardioversion and up to a total treatment duration of 56+/-4 days.
Total Total of all reporting groups

Baseline Measures
    Fondaparinux     UFH/VKA     Total  
Number of Participants  
[units: participants]
 		  174     170     344  
Age [1]
[units: Years]
Mean ± Standard Deviation 		  68.24  ± 11.09     66.78  ± 11.93     67.52  ± 11.52  
Gender [1]
[units: Participants]
 		     
Female     69     60     129  
Male     105     110     215  
[1] Baseline characteristic data were collected in members of the Modified Intent-to-Treat (mITT) Population, comprised of all randomized participants receiving at least one dose of study medication and for whom any post-baseline value was available.



  Outcome Measures
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1.  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   [ 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 ]
  Show Outcome Measure 1

2.  Secondary:   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) ]
  Show Outcome Measure 2

3.  Secondary:   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) ]
  Show Outcome Measure 3

4.  Secondary:   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) ]
  Show Outcome Measure 4

5.  Secondary:   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) ]
  Show Outcome Measure 5

6.  Secondary:   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) ]
  Show Outcome Measure 6

7.  Secondary:   Number of Participants With Primary Successful Electrical Cardioversion (CV) in Sinus Rhythm   [ Time Frame: Day 1 until Day 3 ]
  Show Outcome Measure 7

8.  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   [ Time Frame: At second TEE (at Day 28+/-4) ]
  Show Outcome Measure 8

9.  Secondary:   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) ]
  Show Outcome Measure 9

10.  Secondary:   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) ]
  Show Outcome Measure 10


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


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