Venous ThromboembolismPhase 3SYMPTOMSNCT02379806
The SYMPTOMS - SYstematic Elderly Medical Patients Thromboprophylaxis: Efficacy on Symptomatic OutcoMeS - Study
A Phase 3 study testing Enoxaparin in people with Venous Thromboembolism, run by University Hospital, Brest at 46 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- Venous Thromboembolism
- What is being tested?
- Enoxaparin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,560 participants
- Where
- 46 sitesin 2 countries
- Study dates
- 3 Sep 2015to 29 Dec 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 70 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
46 sites in 2 countries.
46 sites in 2 countries
France45 sites
Centre Hospitalier d'Agen
Agen, 47000
CHU Angers
Angers, 49000
CH Angoulême
Angoulême, 16959
CH d'Arras
Arras, 62022
CH Béthune
Béthune, 62400
Hôpital Jean Verdier (APHP)
Bondy, 93143
CHU Bordeaux
Bordeaux, 33075
HIA Clermont-Tonnerre
Brest, 29200
CHRU Brest
Brest, 29609
CH Public du Cotentin
Cherbourg, 50102
CH Louis Mourier de Colombes
Colombes, 97200
CHU de Dijon
Dijon, 21000
CHU Grenoble
Grenoble, 38700
CHD Vendée
La Roche-sur-Yon, 85925
Groupe Hospitalier Le Havre
Le Havre
CHU Rouen
Le Petit-Quevilly, 76140
CHRU de Lille
Lille, 59000
CHU Limoges
Limoges, 87042
CHD Vendée - Site de Luçon
Luçon, 85400
Hôpital Edouard Herriot - CHU Lyon
Lyon, 69003
CHU Lyon
Lyon, 69495
Hôpital de la Timone - AP-HM
Marseille, 13274
Clinique Mutualiste Médico-chirurgical "Beau Soleil"
Montpellier
CH des Pays de Morlaix
Morlaix, 29600
CHU Nancy
Nancy, 54035
CHU de Nantes
Nantes, 44000
Hôpital Cimiez - CHU Nice
Nice, 03003
HEGP - Paris
Paris, 75000
Hôpital Lariboisiere
Paris, 75000
Hôpital Saint-Antoine (APHP)
Paris, 75012
Hôpital Broca- APHP
Paris, 75013
Hôpita Cochin - APHP
Paris, 75014
Institut Mutualiste Montsouris
Paris, 75014
CH Périgueux
Périgueux, 24019
CHU Poitiers
Poitiers, 86021
CH de Cornouaille - Quimper
Quimper, 29107
CHU Rennes
Rennes, 35203
Hôpital Charles Nicolle- CHU Rouen
Rouen, 76230
CHU La Réunion - Site Félix Guyon
Saint-Denis, 97411
CHU de Saint Etienne
Saint-Etienne, 42000
CHU La Réunion - site du GHSR
Saint-Pierre, 97410
CHRU Strasbourg- Service HTA et Maladies Vasculaires
Strasbourg, 67091
CHU Strasbourg - Service de Médecine Interne
Strasbourg, 67091
CH Intercommunal Toulon La Seyne sur Mer
Toulon, 83056
HIA Sainte-Anne Toulon
Toulon, 83800
About this 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
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.
Read more
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.
- Conditions
- Venous Thromboembolism
- Being tested
- Enoxaparin, Placebo
- Medical subject headings
- Venous Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnoxaparinDrug
Also called Lovenox
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Active enoxaparin 40 mg | Active comparator | One 0.4 ml prefilled syringe containing 40 mg enoxaparin active substance administered once daily for 10 ± 4 days Receives: Drug: Enoxaparin |
| Placebo of enoxaparin 40 mg | Placebo comparator | One 0.4 ml placebo syringe of enoxaparin 40 mg administered once daily for 10 ± 4 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurence of the following events: symptomatic confirmed deep venous thrombosis (DVT), symptomatic confirmed pulmonary embolism (PE), or fatal PE
Measured: Occurence of any of the events through the Day 30 visit
Secondary outcomes (1)
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.
Measured: Occurence of any of the events through the Day 30 and Day 90 visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2015 (estimated)
- Study start3 Sep 2015
- Primary completionDec 2020
- Study completion29 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Venous ThromboembolismStudies of the same condition, open and under way.
- More trials run by University Hospital, BrestThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 2,560 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Brest
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02379806
- Sponsor's protocol ID
- 29BRC14.0012 SYMPTOMS
- Other IDs
- 2014-000311-13, 2014
- Acronym
- SYMPTOMS
- Status last verified
- Jun 2022
- First submitted
- 16 Feb 2015
- Last updated
- 5 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Mottier D, Girard P, Couturaud F, Lacut K, Le Moigne E, Paleiron N, Guellec D, Sanchez O, Cogulet V, Laporte S, Marhic G, Mismetti P, Presles E, Robert-Ebadi H, Mahe I, Plaisance L, Reny JL, Darbellay Farhoumand P, Cuvelier C, Le Henaff C, Lambert Y, Danguy des Deserts M, Rousseau Legrand C, Boutreux S, Bleher Y, Decours R, Trinh-Duc A, Armengol G, Benhamou Y, Daumas A, Guyot SL, De Carvalho H, Lamia B, Righini M, Meyer G, Le Gal G. Enoxaparin versus Placebo to Prevent Symptomatic Venous Thromboembolism in Hospitalized Older Adult Medical Patients. NEJM Evid. 2023 Aug;2(8):EVIDoa2200332. doi: 10.1056/EVIDoa2200332. Epub 2023 Jun 27.
PubMed 38320142
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02379806
- Acronym / sponsor ID
- SYMPTOMS / 29BRC14.0012 SYMPTOMS
- Conditions
- Venous Thromboembolism
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,560 participants (actual)
- Lead sponsor
- University Hospital, BrestUniversity, hospital or other
- Study start
- 3 Sep 2015 (actual)
- Primary completion
- Dec 2020 (actual)
- Study completion
- 29 Dec 2020 (actual)
- First posted
- 5 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active enoxaparin 40 mg | Active comparator | Drug: EnoxaparinOne 0.4 ml prefilled syringe containing 40 mg enoxaparin active substance administered once daily for 10 ± 4 days |
| Placebo of enoxaparin 40 mg | Placebo comparator | Drug: PlaceboOne 0.4 ml placebo syringe of enoxaparin 40 mg administered once daily for 10 ± 4 days |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (17 listed)
- Admission for one of the following reasons:
- Hypersensitivity to heparin
- History of Heparin Induced Thrombocytopenia
- Active bleeding
- Bacterial endocarditis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EnoxaparinAlso: Lovenox | Drug | Active enoxaparin 40 mg |
| Placebo | Drug | Placebo of enoxaparin 40 mg |
Primary outcome
Occurence of the following events: symptomatic confirmed deep venous thrombosis (DVT), symptomatic confirmed pulmonary embolism (PE), or fatal PE
Time frame: Occurence of any of the events through the Day 30 visit
1 secondary outcome
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.
Time frame: Occurence of any of the events through the Day 30 and Day 90 visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2022.
- Derived from this study: PubMed 38320142Mottier D, Girard P, Couturaud F, Lacut K, Le Moigne E, Paleiron N, Guellec D, Sanchez O, Cogulet V, Laporte S, Marhic G, Mismetti P, Presles E, Robert-Ebadi H, Mahe I, Plaisance L, Reny JL, Darbellay Farhoumand P, Cuvelier C, Le Henaff C, Lambert Y, Danguy des Deserts M, Rousseau Legrand C, Boutreux S, Bleher Y, Decours R, Trinh-Duc A, Armengol G, Benhamou Y, Daumas A, Guyot SL, De Carvalho H, Lamia B, Righini M, Meyer G, Le Gal G. Enoxaparin versus Placebo to Prevent Symptomatic Venous Thromboembolism in Hospitalized Older Adult Medical Patients. NEJM Evid. 2023 Aug;2(8):EVIDoa2200332. doi: 10.1056/EVIDoa2200332. Epub 2023 Jun 27.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
46 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Enoxaparin in people with Venous Thromboembolism, run by University Hospital, Brest at 46 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 46 sites in France, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurence of the following events: symptomatic confirmed deep venous thrombosis (DVT), symptomatic confirmed pulmonary embolism (PE), or fatal PE (time frame: Occurence of any of the events through the Day 30 visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02379806, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2022.