Pharmacoepidemiology Treatment of Symptomatic Pulmonary Embolism in Hospitalized Patients Aged 75 Years or More: PEAGE

Study Overview
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Brief Summary
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The treatment of the venous thromboembolic disease, including pulmonary embolism (PE), is based on anticoagulants. During the last decade, all the randomized clinical trials evaluating these anticoagulants have included PE patients with an average age below 60 years. But in clinical pratice, approximately 50% of PE patients are older than 75 years. So the investigators want to perform a french multicentre prospective cohort of consecutive patients receiving an anticoagulant treatment for a symptomatic and confirmed PE. All the validated and available anticoagulant treatments are authorized in this cohort (unfractionnated and low molecular weight heparins, fondaparinux, vitamin K antagonists and direct oral anticoagulants). This cohort will provide data regarding the bleeding risk and the risk of PE recurrences and regarding the pharmacokinetic (PK) and pharmacodynamic (PD) properties of these anticoagulants in this older population. Using population approach modelling , the investigators will pay particular attention to the sources of PK/PD variability PK / PD such as genetic polymorphisms of P-glycoprotein and cytochrome P450. Using all these data , the investigators will try to identify significant risk factors for bleeding and venous thromboembolic events.

Official Title
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Pharmacoepidemiology Treatment of Symptomatic Pulmonary Embolism in Hospitalized Patients Aged 75 Years or More: Prospective, Multicenter Cohort Study PEAGE

Conditions
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Elderly, Pulmonary Embolism, Anticoagulants

Intervention / Treatment
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* Other: 4 blood samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic pulmonary embolism confirmed by objective paraclinical examination with or without DVT associated confirmation of pulmonary embolism within 3 days Administration possible according to the recommended dosages of anticoagulant treatment : (unfractionnated and low molecular weight heparins, fondaparinux, vitamin K antagonists and direct oral anticoagulants) Indication of anticoagulant treatment for at least 6 months Exclusion Criteria: on therapeutic dose of anticoagulant treatment over 72 hours indication to therapeutic dose of anticoagulant treatment for another reason. Inability for whatever reasons, to prescribe recommended anticoagulant treatment PE treatment on heparin-induced thrombocytopenia requiring argatroban, lepirudin or danaparoid treatment, ongoing bleeding PE occurring despite well conducted anticoagulant treatment Contraindications to recommended dose of anticoagulant treatment

Ages Eligible for Study
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Minimum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| PEAGE<br>Patients older than 75 years receiving an anticoagulant treatment for a symptomatic and confirmed PE | Other: 4 blood samples<br>* PK and / or PD measurements during hospitalization<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major bleeding defined by the International Society of Thrombosis & Haemostasis | Bleeding causing a fall in hemoglobin level of 20 g L-1 (1.24 mmol L-1) or more, or leading to transfusion of two or more units of whole blood or red cells., Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, Fatal bleeding | at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically relevant non-major bleeding | defined by: Subcutaneous hematoma spontaneous over 25 cm2 Spontaneous epistaxis for more than 5 minutes Spontaneous or after urinary catheter hematuria for more than 24 hours Significant rectal bleeding Gingival bleeding for more than 5 minutes Bleeding requiring hospitalization and / or a hemostatic action | at 6 months | 
| Recurrent pulmonary embolism | confirmed by CT scan or ventilation/perfusion lung scan | at 6 months | 
| Deep vein thrombosis (recurrence or new) | confirmed by venous doppler ultrasonography or venography of the lower limbs or CT scan | at 6 months | 
| Arterial cardiovascular events | Acute coronary syndrom with or without ST-segment elevation Stroke ischemic or hemorrhagic confirmed by CT scan or magnetic resonance imaging brain Acute ischemic phenomena (lower limbs, mesenteric ...) confirmed by arterial doppler or arteriography. | at 6 months | 
| Death |  | at 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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elderly patients, Pulmonary embolism, Anticoagulant treatments