Use of Direct Oral Anticoagulants (DOACs) in Patients With Ph-negative Myeloproliferative Neoplasms (MPN-DOACs)

Patients with myeloproliferative neoplasms (MPN) are predisposed to have an increased thrombotic and hemorrhagic risk and, in this context, the use of newly approved direct oral anticoagulants (DOACs) may have improved bleeding risk compared to warfarin use. However, the published experience is very limited and does not allow any conclusion. In the cohort of patients with MPN and venous thromboembolism (VTE) of European Leukemia-net, only 3.3% of patients had been treated with DOACs. Similarly, in a recent publication of a series of 760 patients with single-center MPN, only 25 (3.3%) were treated with a DOAC (13 for atrial fibrillation and 12 for thrombotic events).

While it is known that the risk of thrombotic recurrence and haemorrhagic event during warfarin treatment is about 30% at 5 years from the first event, the actual risk of such events in MPN patients is not known.

The aim of the present study is therefore to obtain information on patients with MPN treated with DOAC for atrial fibrillation (AF) and VTE. This is an international multi-center retrospective survey aimed at describing the efficacy / safety of DOAC in the prevention of:

• cardioembolic stroke in patients with MPN with AF
• recurrent thrombosis in patients with MPN with VTE
• major bleeding in all patients with MPN.

The results will allow to design future prospective studies that evaluate the benefit / risk profile of DOAC compared to warfarin in these pathologies characterized by high risk of thrombosis and, in some subgroups, of bleeding.

Study Overview

• Status: Completed
• Conditions: Myeloproliferative Neoplasm
• Intervention / Treatment: Drug: DOACs

• Study Type: Observational
• Enrollment (Actual): 442

Contacts and Locations

Study Locations

• Canada
  • Toronto, Canada
    • Princess Margaret Cancer Centre Toronto
• France
  • Brest, France
    • Centre Hospitalier Universitaire de Brest
• Germany
  • Aachen, Germany
    • RWTH Aachen University
  • Minden, Germany
    • Johannes Wesling Klinikum Minden
• Italy
  • Bergamo, Italy, 24127
    • ASST- Papa Giovanni XXIII - S.I.M.T.
  • Bologna, Italy
    • Policlinico S. Orsola - Malpighi
  • Firenze, Italy
    • AOU Careggi di Firenze
  • Monza, Italy, 20900
    • ASST MONZA Ospedale San Gerardo Clinica Ematologica
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Universitaria Federico II di Napoli Divisione di Ematologia e Trapianti del Midollo
  • Palermo, Italy
    • AOU Policlinico di Palermo
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo S.C Ematologia
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario A. Gemelli IRCCS UCSC Ematologia
  • Torino, Italy, 10126
    • A.O.U. Città della Salute e della Scienza di Torino - Ospedale Molinette- S.C. Ematologia
  • Vicenza, Italy, 36100
    • Ospedale San Bortolo di Vicenza - U.O.C di Ematologia
  • Veneto
    • Verona, Veneto, Italy, 37134
      • Divisione Ematologia, Ospedale Borgo Roma
• Spain
  • Barcellona, Spain, 08034
    • Hospital Clinic, Hematology Department
• United Kingdom
  • London, United Kingdom
    • Guy's and St Thomas' NHS Foundation Trust
• United States
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai New York

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with MPN treated with any DOAC for AF or VTE

Description

Inclusion Criteria:

• diagnosis of Philadelphia-negative MPN according to World Health Organization (WHO) 2008 and/or 2016 criteria until 31/12/2018;
• diagnosis of atrial fibrillation (AF) and/or diagnosis of venous thromboembolism (VTE) including thrombosis of deep veins of the limbs and the abdomen, cerebral and splanchnic veins (hepatic, portal, mesenteric, and splenic veins) and pulmonary embolism;
• treatment with DOACs.

Exclusion Criteria:

• Administration of DOAC for any medical reason other than AF and/or VTE (excluding superficial vein thrombosis)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MPN patients treated with DOACs	Drug: DOACs; Direct Oral Anticoagulants; Other Names: Apixaban; Dabigatran; Edoxaban; Rivaroxaban

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of major thrombosis and bleeding	Cumulative incidence of major arterial and venous thrombosis and major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH)	At 5 year from the start of treatment with DOACs

Collaborators and Investigators

• Sponsor: Fondazione per la Ricerca Ospedale Maggiore

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2019
• Primary Completion (ACTUAL): March 31, 2020
• Study Completion (ACTUAL): December 31, 2020

Study Registration Dates

• First Submitted: December 5, 2019
• First Submitted That Met QC Criteria: December 6, 2019
• First Posted (ACTUAL): December 10, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 21, 2021
• Last Update Submitted That Met QC Criteria: February 19, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Real world data; Direct oral anticoagulants; Efficacy and safety profile
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Neoplasms; Myeloproliferative Disorders; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Dabigatran; Apixaban; Edoxaban
• Other Study ID Numbers: MPN-DOACs

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No