Apixaban for Extended Anticoagulation (APIDULCIS)

NCT03678506 | Terminated Phase 4 DMC

• 2 other identifiers: FAA I1. 7-2017 (APIDULCIS)2017 002340 32
• Study Type: interventional
• Target: 800
• Locations: 1 country
• Sites: 1

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.

Conditions

Venous Thromboembolism; Anticoagulants

Keywords

Venous thromboembolism; D-Dimer; Apixaban; Extended treatment

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (4)

• Number of and rate of thromboembolic events

  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

  18 months

• Number and rate of non major bleeding complications

  From date of enrollment until the date of first documented event assessed up to18 months

• Number and rate of dead patients (overall mortality)

  From date of enrollment until the date of first documented event assessed up to 18 months

Study Arms (2)

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.

Drug: Apixaban

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.

Interventions

Apixaban DRUG

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

Also known as: Apixaban and positive d-dimer

Positive D-Dimer

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Arianna Anticoagulazione Foundation: lead

Study Sites (1)

Daniela Poli

Florence, 50134, Italy

Location

Related Publications (1)

• 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.

  PMID: 35914222 DERIVED

MeSH Terms

Conditions

Venous Thromboembolism

Interventions

apixaban

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Daniela Poli, MD

  Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 8, 2018
• First Posted: September 19, 2018
• Study Start: August 16, 2018
• Primary Completion: September 1, 2021
• Study Completion: January 31, 2023
• Last Updated: February 24, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 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
• Access Criteria: Data access requests will be reviewed by the Scientific board of the study.

Locations

IT (1)