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| ID | Type | Description | Link |
|---|---|---|---|
| 2017 002340 32 | EudraCT Number |
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The study was interrupted after a planned interim analysis for the high rate of primary outcomes (7.3%; 95% confidence interval [CI], 4.5-11.2)
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The study aims at optimizing the long-term and extended management of patients with a first episode of venous thromboembolism (proximal deep vein thrombosis with or without pulmonary embolism) (VTE). Patients at high risk of recurrence (with altered D-dimer test), who had received anticoagulation (whatever the drug used) for 12-15 months after the first episode of thrombosis, will be treated with Apixaban 2,5 mg x 2 for 18 months as extended treatment. Patients at low risk, with normal D-dimer test, will stop anticoagulation definitely.
This prospective cohort study aims to assess the efficacy and safety of a management procedure to decide on giving or not an extended anticoagulation (administering apixaban 2 2.5 mg twice daily ) to outpatients with a single episode of proximal deep vein thrombosis of the lower limbs and/or pulmonary embolism who had received 12-15 months of anticoagulation (whatever the anticoagulant drug used). The study seeks to assess whether a management procedure involving D-dimer testing assessment can identify a subset of subjects at low risk of recurrence in whom an extended anticoagulation can be safely avoided.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Positive D-Dimer | Experimental | At the first positive D-dimer results (during anticoagulation or after its temporary withdrawal) the patients are invited to assume Eliquis (apixaban) 2.5 mg twice daily, and continue this therapy for the following 18 months. |
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| Negative D-Dimer | No Intervention | Patients with persistently negative results at the four serial D-dimer measurements, stay definitively without anticoagulation and discouraged to resume any antithrombotic drug for secondary VTE prevention. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Apixaban | Drug | Apixaban 2.5 mg x 2 will be administered to patients with positive D-dimer results |
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| Measure | Description | Time Frame |
|---|---|---|
| Number and rate of patients with confirmed recurrent VTE and VTE-related death (efficacy). | The occurrence of proximal deep vein thrombosis with or without pulmonary embolism (new or recurrent episode) wil be recorded in all patients | From date of enrollment until the date of first documented event assessed up to 18 months |
| Number and rate of major Bleeding events (defined according to International Society on Thrombosis and Haemostasis guidelines (safety) | Fatal bleeding; intracranial; intraspinal; intraocular; pericardial; intra-articular; intramuscular with compartment syndrome; retroperitoneal,; acute clinically overt bleeding will be recorded in all patients | From date of enrollment until the date of first documented event assessed up to18 months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of and rate of thromboembolic events | Transient ischemic attack (TIA), Stroke, Myocardial infarction will be recorded in all patients | From date of enrollment until the date of first documented event assessed up to 18 months |
| Presence of severe post-thrombotic syndrome according to Villalta Score |
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Inclusion Criteria:
Exclusion Criteria:
A) Exclusion criteria regarding the index event
Events usually associated with low risk of recurrence
Deep vein thrombosis/ Pulmonary embolism occurred within 3 months from major surgery or major trauma
Isolated Distal deep vein thrombosis (thrombosis of calf veins)
Events associated with a very high risk of recurrence or occurrence of life-threatening recurrent events
Index venous thromboembolic event in different sites than deep veins of the lower limbs or pulmonary arteries
B) Exclusion criteria present at the moment of patients' screening:
Age younger than 18 or older than 75 years
More documented unprovoked venous thromboembolic episodes
Pregnancy or puerperium
Severe post-thrombotic syndrome (≥ 15 points at the Villalta score)
Solid neoplasia or blood disease in active phase or requiring chemotherapy/radiotherapy
All the clinical conditions requiring prolonged treatment with Low Molecular Weight Heparin
Presence of overt, active chronic diseases (i.e. inflammatory bowel disease)
Known serious thrombophilic alterations:
Presence of antiphospholipid syndrome
Presence of vein cava filter
Concomitant conditions (such as atrial fibrillation) requiring indefinite anticoagulation
Severe cardio-respiratory insufficiency (NYHA 3 or 4)
Any absolute contraindications to anticoagulation treatment
Any other contraindications to Apixaban as per local SmPC
Life expectancy shorter than 1 year
Refuse interruption of anticoagulation to perform serial D-dimer assessment
Geographically inaccessible location
Inability or refusal to give consent
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| Name | Affiliation | Role |
|---|---|---|
| Daniela Poli, MD | Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Daniela Poli | Florence | 50134 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35914222 | Derived | Palareti G, Poli D, Ageno W, Legnani C, Antonucci E, Bucherini E, Testa S, Paoletti O, Chistolini A, Serrao A, Martinelli I, Bucciarelli P, Falanga A, Tosetto A, Sarti L, Mastroiacovo D, Cosmi B, Visona A, Santoro RC, Zanatta N, Grandone E, Bertu L, Pengo V, Caiano L, Prandoni P. D-dimer and reduced-dose apixaban for extended treatment after unprovoked venous thromboembolism: the Apidulcis study. Blood Adv. 2022 Dec 13;6(23):6005-6015. doi: 10.1182/bloodadvances.2022007973. |
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All collected data will be shared
The data will be available after the publication of global results of the study or after 18 months from the enrollment of the last patients
Data access requests will be reviewed by the Scientific board of the study.
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 16, 2018 | Sep 12, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 16, 2018 | Sep 12, 2018 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D054556 | Venous Thromboembolism |
| ID | Term |
|---|---|
| D013923 | Thromboembolism |
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| C522181 | apixaban |
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The patients included in the study will receive a serial determination of D-dimer assay (a maximum of four determinations in case of negative results).The D-dimer measurements should be performed at the moment of patient screening, when patients still assume their anticoagulant treatment (T0), at 15±2 days (T1), 30±4 days (T2), and 60±5 (T3) days after their anticoagulant treatment has been stopped. At the first positive D-dimer result patients resume anticoagulation with apixaban 2.5 mg bis in die for the next 18 months. Patients with negative D-Dimer results at all determinations stop anticoagulation definitely and will followed up for the next 18 months.
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Patient with deep vein thrombosis as index event will be evaluated, at the and of follow-up, applying Villalta score, commonly used to diagnose post-thrombotic syndrome in the subacute phase of thrombosis. The presence of venous ulcer of the leg or a score > of 15 points indicate the occurrence of severe post-thrombotic syndrome. The maximum score is 33. The score from 5 to 9 points indicate mild post-thrombotic syndrome and from 10 to 15 points indicate moderate post-thrombotic syndrome |
| 18 months |
| Number and rate of non major bleeding complications | In all patients will be recorded any sign or symptom of hemorrhage that does not fit the criteria for the definition of major bleeding but does meet at least one of the following criteria: 1)requiring medical intervention by a healthcare professional; 2) leading to hospitalization or increased level of care;3) prompting a face to face evaluation | From date of enrollment until the date of first documented event assessed up to18 months |
| Number and rate of dead patients (overall mortality) | VTE-related death; cardiovascular related-death; bleeding-related death; death for: cancer, infectious disease and unknown cause; sudden death will be recorded in all patients | From date of enrollment until the date of first documented event assessed up to 18 months |