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

Regional University Hospital Center (CHRU)

Status and phase

Completed

Phase 3

Conditions

Venous Thromboembolism

Treatments

Drug: Enoxaparin

Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT02379806

29BRC14.0012 SYMPTOMS

2014-000311-13 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment

2,560 patients

Sex

All

Ages

70+ years old

Volunteers

No Healthy Volunteers

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