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

Phase 3
Completed
Conditions
Venous Thromboembolism
Interventions
Drug: Placebo
Registration Number
NCT02379806
Lead Sponsor
University Hospital, Brest
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
2560
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo of enoxaparin 40 mgPlaceboOne 0.4 ml placebo syringe of enoxaparin 40 mg administered once daily for 10 ± 4 days
Active enoxaparin 40 mgEnoxaparinOne 0.4 ml prefilled syringe containing 40 mg enoxaparin active substance administered once daily for 10 ± 4 days
Primary Outcome Measures
NameTimeMethod
Occurence of the following events: symptomatic confirmed deep venous thrombosis (DVT), symptomatic confirmed pulmonary embolism (PE), or fatal PEOccurence of any of the events through the Day 30 visit
Secondary Outcome Measures
NameTimeMethod
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.Occurence of any of the events through the Day 30 and Day 90 visit

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.

Trial Locations

Locations (46)

CH Public du Cotentin

🇫🇷

Cherbourg, France

CH Louis Mourier de Colombes

🇫🇷

Colombes, France

CHD Vendée

🇫🇷

La Roche Sur Yon, France

Groupe Hospitalier Le Havre

🇫🇷

Le Havre, France

CHRU de Lille

🇫🇷

Lille, France

CHU Limoges

🇫🇷

Limoges, France

CHD Vendée - Site de Luçon

🇫🇷

Luçon, France

Clinique Mutualiste Médico-chirurgical "Beau Soleil"

🇫🇷

Montpellier, France

CH des Pays de Morlaix

🇫🇷

Morlaix, France

CHU Lyon

🇫🇷

Lyon, France

CHU Nancy

🇫🇷

Nancy, France

CHU de Nantes

🇫🇷

Nantes, France

Hôpital Cimiez - CHU Nice

🇫🇷

Nice, France

HEGP - Paris

🇫🇷

Paris, France

Hôpital Lariboisiere

🇫🇷

Paris, France

Hôpital Saint-Antoine (APHP)

🇫🇷

Paris, France

Hôpital Broca- APHP

🇫🇷

Paris, France

CHU Poitiers

🇫🇷

Poitiers, France

CH de Cornouaille - Quimper

🇫🇷

Quimper, France

CHU de Dijon

🇫🇷

Dijon, France

CHU Bordeaux

🇫🇷

Bordeaux, France

CHU Grenoble

🇫🇷

Grenoble, France

CHU Rouen

🇫🇷

Le Petit Quevilly, France

Hôpital de la Timone - AP-HM

🇫🇷

Marseille, France

Hôpital Edouard Herriot - CHU Lyon

🇫🇷

Lyon, France

CH Périgueux

🇫🇷

Perigueux, France

Hôpita Cochin - APHP

🇫🇷

Paris, France

Institut Mutualiste Montsouris

🇫🇷

Paris, France

HIA Clermont-Tonnerre

🇫🇷

Brest, France

CHRU Brest

🇫🇷

Brest, France

CH Béthune

🇫🇷

Béthune, France

Hôpital Jean Verdier (APHP)

🇫🇷

Bondy, France

Centre Hospitalier d'Agen

🇫🇷

Agen, France

CHU Angers

🇫🇷

Angers, France

CH Angoulême

🇫🇷

Angouleme, France

CH d'Arras

🇫🇷

Arras, France

CHU Rennes

🇫🇷

Rennes, France

Hôpital Charles Nicolle- CHU Rouen

🇫🇷

Rouen, France

CHU La Réunion - Site Félix Guyon

🇫🇷

Saint Denis, France

CHU de Saint Etienne

🇫🇷

Saint Etienne, France

CHU La Réunion - site du GHSR

🇫🇷

Saint Pierre, France

CHRU Strasbourg- Service HTA et Maladies Vasculaires

🇫🇷

Strasbourg, France

CHU Strasbourg - Service de Médecine Interne

🇫🇷

Strasbourg, France

CH Intercommunal Toulon La Seyne sur Mer

🇫🇷

Toulon, France

HIA Sainte-Anne Toulon

🇫🇷

Toulon, France

Hôpitaux Universitaires de Genève

🇨🇭

Genève, Switzerland

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