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

Venous Thromboembolism Clinical Trial

— SYMPTOMS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02379806
• Other study ID #: 29BRC14.0012 SYMPTOMS
• Secondary ID: 2014-000311-13
• Status: Completed
• Phase: Phase 3
• Start date: September 3, 2015
• Est. completion date: December 29, 2020

Study information

• Verified date: June 2022
• Source: University Hospital, Brest
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2560
• Est. completion date: December 29, 2020
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Thromboembolism
• Venous Thromboembolism

Intervention

Drug:
• Enoxaparin

• Placebo

Locations

Country	Name	City	State
France	Centre Hospitalier d'Agen	Agen
France	CHU Angers	Angers
France	CH Angoulême	Angouleme
France	CH d'Arras	Arras
France	CH Béthune	Béthune
France	Hôpital Jean Verdier (APHP)	Bondy
France	CHU Bordeaux	Bordeaux
France	CHRU Brest	Brest
France	HIA Clermont-Tonnerre	Brest
France	CH Public du Cotentin	Cherbourg
France	CH Louis Mourier de Colombes	Colombes
France	CHU de Dijon	Dijon
France	CHU Grenoble	Grenoble
France	CHD Vendée	La Roche Sur Yon
France	Groupe Hospitalier Le Havre	Le Havre
France	CHU Rouen	Le Petit Quevilly
France	CHRU de Lille	Lille
France	CHU Limoges	Limoges
France	CHD Vendée - Site de Luçon	Luçon
France	CHU Lyon	Lyon
France	Hôpital Edouard Herriot - CHU Lyon	Lyon
France	Hôpital de la Timone - AP-HM	Marseille
France	Clinique Mutualiste Médico-chirurgical "Beau Soleil"	Montpellier
France	CH des Pays de Morlaix	Morlaix
France	CHU Nancy	Nancy
France	CHU de Nantes	Nantes
France	Hôpital Cimiez - CHU Nice	Nice
France	HEGP - Paris	Paris
France	Hôpita Cochin - APHP	Paris
France	Hôpital Broca- APHP	Paris
France	Hôpital Lariboisiere	Paris
France	Hôpital Saint-Antoine (APHP)	Paris
France	Institut Mutualiste Montsouris	Paris
France	CH Périgueux	Perigueux
France	CHU Poitiers	Poitiers
France	CH de Cornouaille - Quimper	Quimper
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
Switzerland	Hôpitaux Universitaires de Genève	Genève

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Brest

Countries where clinical trial is conducted

France,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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