Atrial fibrillation (AF) MedDRA version: 9.1 Level: LLT Classification code 10003658 Term: Atrial fibrillation
Conditions
Interventions
Trade Name: Arixtra 2.5 mg Injection
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Fondaparinux sodium
Current Sponsor code: GSK576428
Concentration unit: mg/ml milligram(s)/millili
Sponsors
GlaxoSmithKline R & D
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for enrolment in the study must meet all of the following 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 • Eligibility for electrical cardioversion Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria must not be enrolled in the study: • Exclusion criteria related to disease characteristics at presentation: Evidence of acute ischemia, hypotension, or other symptoms which would require immediate cardioversion No documented sinus rhythm on ECG [or other documentation of sinus rhythm, i.e., physician’s note] for more than 1 year, Acute neurological deficits (TIA, stroke, intracranial bleeding), or known other disease which may cause neurological deficits (e.g., multiple sclerosis, seizure disorder), Known left ventricular or aortic thrombus, Treatment with antithrombotic agents, including low-dose anticoagulation, for more than 48 hours prior to randomisation (this refers to anticoagulation for the current episode of AF; patients who previously received anticoagulation are eligible), Treatment with oral NSAIDs or ASA at doses greater than 325 mg per day for more than 72 hours prior to randomisation, Known symptomatic or asymptomatic thromboembolism or history of documented DVT or PE within the last six months. • Exclusion criteria related to concomitant medication: Anticoagulant therapy required or likely to be required during the study period (e.g. planned surgery justifying pharmacological thromboprophylaxis), 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). • Exclusion criteria related to study treatments: Known hypersensitivity to UFH, VKA, or Fondaparinux or one of these drugs’ excipients, History of heparin-associated thrombocytopenia (Type II), Women of childbearing potential not using a reliable contraceptive method throughout the study period (a list of reliable contraceptive methods is provided in the accompanying SPM), Pregnant or breast-feeding women during the study period. • Exclusion criteria based on risk of bleeding: Active, clinically significant bleeding or clinically significant bleeding within the past month, Patient judged by the investigator to be at high risk of bleeding, Major surgery within the previous three months, Ophthalmic, spinal, and/or brain surgery within the previous twelve months, Haemorrhagic stroke within the previous twelve months, Severe head injury within the previous twelve months, Documented congenital or acquired bleeding tendency/disorder(s), Previous (within 12 months) or active or currently treated peptic ulcer disease, Uncontrolled arterial hypertension (persistent systolic blood pressure over 180 mm Hg or diastolic blood pressure over 110 mm Hg), Bacterial endocarditis, Severe hepatic impairment (Child-Pugh score Class B or C), Platelet count below 100×109/L, Hyperthyroidism, Calculated creatinine clearance < 30 mL/min, Body weight < 50 kg. • Other exclusion criteria related to trial methodology: Planned surgery or intervention within the next 65 days (including catheter ablation procedures as treatment of AF), Any condition that could prevent the patient from providing written informed consent or from adhering to study treatment, including medicine, drug, or alcohol abuse, Life expectancy under six months, Participation in any study using an investigational drug during the previous three months, Patient in whom follow-up to Day 90 is unlikely to be feasible (e.g. patient moving to another country).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to demonstrate non-inferiority of Fondaparinux once daily versus UFH/oral anticoagulation with respect to the occurrence of cerebral neurologic events, systemic thromboembolism, death from any cause, and major bleeding events (combined primary endpoint) during the whole treatment period, i.e., from randomisation up to 4 days after the last administration of study drug. In patients in whom a thrombus could be excluded in the first TEE, this period will generally extend from randomisation until Day 32±4 (28±4 days of treatment + 4 days). In patients who underwent a 28±4 days-period of treatment before thrombus disappearance could be documented in a second TEE, this period will generally extend from randomisation until Day 60±4 (56±4 days of administration of study medication for + 4 days).;Secondary Objective: The secondary objectives are to compare the effects of Fondaparinux once daily versus UFH/oral anticoagulation on the separate components of the combined primary efficacy/safety endpoint, thrombus disappearance, alternative bleeding definitions, success of electrical CV, utilization of resources, and patient compliance with their assigned therapy.;Primary end point(s): The primary endpoint is composed of efficacy (cerebral neurologic events, systemic thromboembolism) and safety events (death from any cause and major bleeding events) occurring during the whole treatment period, i.e., from randomisation up to 4 days after the last administration of study drug. | — |
Countries
France, Germany
Outcome results
None listed