The SYMPTOMS - SYstematic Elderly Medical Patients Thromboprophylaxis: Efficacy on Symptomatic OutcoMeS - Study

Study Overview
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Brief Summary
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Venous thromboembolism (VTE) is a frequent condition, affecting 1.8 per 1,000 people every year. Admission to hospital is one of the main risk factors for VTE, and could account for up to 20% of all VTE, making VTE prevention in admitted patients an appealing option to reduce VTE global burden. The landmark MEDENOX trial and others demonstrated the efficacy of low molecular weight heparins (LMWH) in reducing a composite outcome of symptomatic and asymptomatic events, the latter accounting for the vast majority of events. Publication of these trials led to the implementation of thromboprophylaxis policies in hospitals, which acceptance has been variable. More recently, the use of thromboprophylaxis has been challenged after the publication of 1) a negative trial that used 'death from any cause' as main outcome, 2) a systematic review showing the lack of a clear efficacy on the risk of pulmonary embolism or death, 3) negative trials using new oral anticoagulants, 4) the last version of the American College of Chest Physicians Guidelines, focusing on symptomatic events only, downgraded its recommendation for thromboprophylaxis in medical patients to a 1B recommendation, restricting its use to patients 'at increased risk of thrombosis' and recommending against the use of thromboprophylaxis in patients at low risk of thrombosis, patients bleeding or at high risk of bleeding. However, a limitation of this interpretation of the data is that in most trials, patients with screened asymptomatic events were treated with anticoagulants, preventing the occurrence of symptomatic events during follow-up. Moreover, subgroup analyses showed that elderly patients were at high risk of thrombosis in these trials, and that LMWH could be particularly efficient in this subgroup of patients. Conversely, their risk of bleeding is also higher than in younger patients and the current trials were not powered to detect a difference in the bleeding risk between groups. Finally, the diagnostic and therapeutic management of VTE is more challenging in the elderly. Therefore, we planned a randomized controlled trial on the efficacy of LMWH for the prevention of symptomatic VTE in elderly patients.

Official Title
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Prevention of Symptomatic Venous Thromboembolism by Low Molecular Weight Heparin in Hospitalized Medical Patients Aged 70 Years and Older : a Randomized Placebo-Controlled Study The SYMPTOMS (SYstematic Elderly Medical Patients Thromboprophylaxis : Efficacy on Symptomatic OutcoMeS) Study

Conditions
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Venous Thromboembolism

Intervention / Treatment
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* Drug: Enoxaparin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient aged 70 years or older Admitted to hospital for an acute medical illness Anticipated duration of hospitalization of at least 4 days Life expectancy of at least 3 months Exclusion Criteria: Admission for one of the following reasons: Planned medical procedure. Routine health assessment requiring admission for baseline/trending of health status (e.g., routine colonoscopy). Admission encountered for another life circumstance that causes no bearing on health status and requires no medical intervention (e.g., lack of housing, economic inadequacy, care-giver respite, family circumstances, administrative). Hypersensitivity to heparin History of Heparin Induced Thrombocytopenia Active bleeding Bacterial endocarditis Platelet count of less than 80,000 per cubic millimeter Patients who require anticoagulant therapy for any indication, and those who received any type of anticoagulant therapy for > 48 hours Organic lesion prone to bleeding. Hemorrhagic events or bleeding tendency due to hemostasis disorders. Concomitant use of aspirin (> 160 mg/day), clopidogrel (> 75 mg/day), or of combined antiplatelet therapy Creatinine clearance < 15 ml/min Unable or unwilling to consent Ischemic stroke + hemorrhagic transformation Patient requiring admission to Intensive Care Unit

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active enoxaparin 40 mg<br>One 0.4 ml prefilled syringe containing 40 mg enoxaparin active substance administered once daily for 10 ± 4 days | Drug: Enoxaparin<br> <br> * Other names: Lovenox;|
| Placebo Comparator: Placebo of enoxaparin 40 mg<br>One 0.4 ml placebo syringe of enoxaparin 40 mg administered once daily for 10 ± 4 days | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurence of the following events: symptomatic confirmed deep venous thrombosis (DVT), symptomatic confirmed pulmonary embolism (PE), or fatal PE |  | Occurence of any of the events through the Day 30 visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurence of the following events: Major bleeding, clinically relevant non major bleeding, symptomatic confirmed VTE (DVT or PE) or fatal PE, atherothrombotic cardiovascular events, cardiovascular death, Death from any cause. | The secondary outcomes is the occurrence of any of the following events: Major bleeding as defined by the criteria of the International Society of Thrombosis and Haemostasis at day 30 and day 90 Clinically relevant non major bleeding and any bleeding at day 30 and day 90 Symptomatic confirmed VTE (DVT or PE) or fatal PE through the day 90 visit Atherothrombotic cardiovascular events at day 30 and day 90 Cardiovascular death at day 30 and day 90 Death from any cause at day 30 and day 90 Rate of VTE and bleeding events at day 30 and day 90 according to creatinin clearance (< 50 ml/min and ≥ 50 ml/min), age range, D-dimer level and the use or not of antiplatelet therapy to identified the population at risk for VTE and bleeding. | Occurence of any of the events through the Day 30 and Day 90 visit |