Clinical trial NCT02379806: The SYMPTOMS - SYstematic Elderly Medical Patients Thromboprophylaxis: Efficacy on Symptomatic OutcoMeS - Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Venous Thromboembolism
Lead sponsor: University Hospital, Brest
Sponsor class: OTHER
First posted: 2015-03-05
Enrollment: 2560
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Occurence of the following events: symptomatic confirmed deep venous thrombosis (DVT), symptomatic confirmed pulmonary embolism (PE), or fatal PE
timeFrame: Occurence of any of the events through the Day 30 visit
Secondary outcomes:
measure: 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.
timeFrame: Occurence of any of the events through the Day 30 and Day 90 visit
Other outcomes:
Locations:
city: Agen
country: France
facility: Centre Hospitalier d'Agen
city: Angers
country: France
facility: CHU Angers
city: Angouleme
country: France
facility: CH Angoulême
city: Arras
country: France
facility: CH d'Arras
city: Bondy
country: France
facility: Hôpital Jean Verdier (APHP)
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Brest
country: France
facility: HIA Clermont-Tonnerre
city: Brest
country: France
facility: CHRU Brest
city: Béthune
country: France
facility: CH Béthune
city: Cherbourg
country: France
facility: CH Public du Cotentin
city: Colombes
country: France
facility: CH Louis Mourier de Colombes
city: Dijon
country: France
facility: CHU de Dijon
city: Grenoble
country: France
facility: CHU Grenoble
city: La Roche Sur Yon
country: France
facility: CHD Vendée
city: Le Havre
country: France
facility: Groupe Hospitalier Le Havre
city: Le Petit Quevilly
country: France
facility: CHU Rouen
city: Lille
country: France
facility: CHRU de Lille
city: Limoges
country: France
facility: CHU Limoges
city: Luçon
country: France
facility: CHD Vendée - Site de Luçon
city: Lyon
country: France
facility: Hôpital Edouard Herriot - CHU Lyon
city: Lyon
country: France
facility: CHU Lyon
city: Marseille
country: France
facility: Hôpital de la Timone - AP-HM
city: Montpellier
country: France
facility: Clinique Mutualiste Médico-chirurgical "Beau Soleil"
city: Morlaix
country: France
facility: CH des Pays de Morlaix
city: Nancy
country: France
facility: CHU Nancy
city: Nantes
country: France
facility: CHU de Nantes
city: Nice
country: France
facility: Hôpital Cimiez - CHU Nice
city: Paris
country: France
facility: HEGP - Paris
city: Paris
country: France
facility: Hôpital Lariboisiere
city: Paris
country: France
facility: Hôpital Saint-Antoine (APHP)
city: Paris
country: France
facility: Hôpital Broca- APHP
city: Paris
country: France
facility: Hôpita Cochin - APHP
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Perigueux
country: France
facility: CH Périgueux
city: Poitiers
country: France
facility: CHU Poitiers
city: Quimper
country: France
facility: CH de Cornouaille - Quimper
city: Rennes
country: France
facility: CHU Rennes
city: Rouen
country: France
facility: Hôpital Charles Nicolle- CHU Rouen
city: Saint Denis
country: France
facility: CHU La Réunion - Site Félix Guyon
city: Saint Etienne
country: France
facility: CHU de Saint Etienne
city: Saint Pierre
country: France
facility: CHU La Réunion - site du GHSR
city: Strasbourg
country: France
facility: CHRU Strasbourg- Service HTA et Maladies Vasculaires
city: Strasbourg
country: France
facility: CHU Strasbourg - Service de Médecine Interne
city: Toulon
country: France
facility: CH Intercommunal Toulon La Seyne sur Mer
city: Toulon
country: France
facility: HIA Sainte-Anne Toulon
city: Genève
country: Switzerland
facility: Hôpitaux Universitaires de Genève
Study officials:
References: