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Venous ThromboembolismPhase 4APIDULCISNCT03678506

Apixaban for Extended Anticoagulation (APIDULCIS)

A Phase 4 study testing Apixaban in people with Venous Thromboembolism and Anticoagulants, run by Arianna Anticoagulazione Foundation at 1 site in Italy.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Venous Thromboembolism, Anticoagulants
What is being tested?
Apixaban
Could I receive a placebo?
No, everyone receives an active treatment
How many people
800 participants
Where
1 siteItaly
Study dates
16 Aug 2018to 31 Jan 2023
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 32Show fewer
  • 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
  • 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

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Daniela Poli

    Florence, 50134

Other trials in Italy

About this study

Official title: 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.

Read the 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.

Being tested
Apixaban
Keywords
Venous thromboembolism, D-Dimer, Apixaban, Extended treatment
Medical subject headings
Venous Thromboembolism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ApixabanDrug

    Also called Apixaban and positive d-dimer

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

Study groups in NCT03678506
Study groupRoleWhat they receive
Positive D-DimerExperimentalAt 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.
Receives: Drug: Apixaban
Negative D-DimerNo interventionPatients 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 being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

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

  2. 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

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

Secondary outcomes (4)

  1. Number of and rate of thromboembolic events

    Transient ischemic attack (TIA), Stroke, Myocardial infarction will be recorded in all patients

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

  2. Presence of severe post-thrombotic syndrome according to Villalta Score

    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

    Measured: 18 months

  3. 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

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

  4. 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

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2018
  2. Study start16 Aug 2018
  3. Primary completion1 Sep 2021
  4. Study completion31 Jan 2023

Why it stopped: 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)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
800 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03678506
Sponsor's protocol ID
FAA I1. 7-2017 (APIDULCIS)
Other IDs
2017 002340 32, 2017
Acronym
APIDULCIS
Status last verified
Feb 2023
First submitted
8 Sep 2018
Last updated
24 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: All collected data will be shared

Publications

  • 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.

    PubMed 35914222

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Apixaban in people with Venous Thromboembolism and Anticoagulants, run by Arianna Anticoagulazione Foundation at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: 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)). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03678506, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2023.

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