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Apixaban for Extended Anticoagulation (APIDULCIS) (APIDULCIS)

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ClinicalTrials.gov Identifier: NCT03678506
Recruitment Status : Recruiting
First Posted : September 19, 2018
Last Update Posted : March 19, 2021
Sponsor:
Information provided by (Responsible Party):
Arianna Anticoagulazione Foundation

Tracking Information
First Submitted Date  ICMJE September 8, 2018
First Posted Date  ICMJE September 19, 2018
Last Update Posted Date March 19, 2021
Actual Study Start Date  ICMJE August 16, 2018
Estimated Primary Completion Date October 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 17, 2019)
  • 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
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: September 18, 2018)
  • Number and rate of patients witn 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
  • 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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2018)
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Apixaban for Extended Anticoagulation (APIDULCIS)
Official Title  ICMJE APIDULCIS: Extended Anticoagulation With Low-dose Apixaban After a Standard Course Anticoagulation in Patients With a First Venous Thromboembolism Who Have Positive D-dimer
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Prevention
Condition  ICMJE
  • Venous Thromboembolism
  • Anticoagulants
Intervention  ICMJE Drug: Apixaban
Apixaban 2.5 mg x 2 will be administered to patients with positive D-dimer results
Other Name: Apixaban and positive d-dimer
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Apixaban
  • 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.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 18, 2018)
1200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2023
Estimated Primary Completion Date October 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Cristina Legnani, BSc, PhD 0039 051 2812339 c.legnani@fondazionearianna.org
Contact: Emilia Antonucci, CR 0039 051 4291116 e.antonucci@fondazionearianna.org
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03678506
Other Study ID Numbers  ICMJE FAA I1. 7-2017 (APIDULCIS)
2017 002340 32 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: All collected data will be shared
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (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.
Responsible Party Arianna Anticoagulazione Foundation
Study Sponsor  ICMJE Arianna Anticoagulazione Foundation
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Daniela Poli, MD Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy
PRS Account Arianna Anticoagulazione Foundation
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP