Apixaban for Extended Anticoagulation (APIDULCIS) (APIDULCIS)

February 22, 2023 updated by: Arianna Anticoagulazione Foundation

APIDULCIS: Extended Anticoagulation With Low-dose Apixaban After a Standard Course Anticoagulation in Patients With a First Venous Thromboembolism Who Have Positive D-dimer

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

800

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Firenze, Italy, 50134
        • Daniela Poli

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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:

  • 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

    • 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

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:

    • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Apixaban
Apixaban 2.5 mg x 2 will be administered to patients with positive D-dimer results
Other Names:
  • Apixaban and positive d-dimer
No Intervention: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number and rate of patients with confirmed recurrent VTE and VTE-related death (efficacy).
Time Frame: From date of enrollment until the date of first documented event assessed up to 18 months
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)
Time Frame: From date of enrollment until the date of first documented event assessed up to18 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of and rate of thromboembolic events
Time Frame: From date of enrollment until the date of first documented event assessed up to 18 months
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
Time Frame: 18 months
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
Time Frame: From date of enrollment until the date of first documented event assessed up to18 months
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)
Time Frame: From date of enrollment until the date of first documented event assessed up to 18 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Arianna Anticoagulazione Foundation

Investigators

  • Study Director: Daniela Poli, MD, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 16, 2018

Primary Completion (Actual)

September 1, 2021

Study Completion (Actual)

January 31, 2023

Study Registration Dates

First Submitted

September 8, 2018

First Submitted That Met QC Criteria

September 18, 2018

First Posted (Actual)

September 19, 2018

Study Record Updates

Last Update Posted (Actual)

February 24, 2023

Last Update Submitted That Met QC Criteria

February 22, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FAA I1. 7-2017 (APIDULCIS)
  • 2017 002340 32 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All collected data will be shared

IPD Sharing 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

IPD Sharing Access Criteria

Data access requests will be reviewed by the Scientific board of the study.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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