Apixaban for Extended Anticoagulation (APIDULCIS)

NCT ID: NCT03678506

Last Updated: 2023-02-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 800 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-16
• Study Completion Date: 2023-01-31

Brief Summary

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.

Detailed Description

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.

Conditions

Venous Thromboembolism; Anticoagulants

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Positive D-Dimer

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.

Group Type: EXPERIMENTAL

Apixaban

Intervention Type: DRUG

Apixaban 2.5 mg x 2 will be administered to patients with positive D-dimer results

Negative D-Dimer

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Apixaban

Apixaban 2.5 mg x 2 will be administered to patients with positive D-dimer results

Intervention Type: DRUG

Other Intervention Names

Apixaban and positive d-dimer

Eligibility Criteria

Inclusion Criteria

• First unprovoked Venous Thromboembolic Event
• Venous Thromboembolic events associated with one or more risk factors that are no longer present
• Age older than 18 or younger than 75 years
• Capacity to give written informed consent

Exclusion Criteria

• 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

• Pulmonary Embolism episode with shock or life-threatening
• Isolated pulmonary embolism with a systolic pulmonary artery pressure > 60 mmHg at presentation
• Deep vein thrombosis/ Pulmonary embolism associated with active cancer, antiphospholipid syndrome or long-standing medical illnesses
• More than one idiopathic event
• Index venous thromboembolic event in different sites than deep veins of the lower limbs or pulmonary arteries

• 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:

• deficiencies of natural anticoagulants (Antithrombin, Protein C, Protein S)
• homozygosity for Factor V Leiden or Factor II G20210A mutations
• double heterozygosity
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Arianna Anticoagulazione Foundation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniela Poli, MD

Role: STUDY_DIRECTOR

Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy

Locations

Daniela Poli

Florence, , Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 35914222 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017 002340 32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

FAA I1. 7-2017 (APIDULCIS)

Identifier Type: -

Identifier Source: org_study_id