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Polycythemia VeraPhase 3AVAJAKNCT05198960

AVAJAK: Apixaban/Rivaroxaban Versus Aspirin for Primary Prevention of Thrombo-embolic Complications in JAK2V617F-positive Myeloproliferative Neoplasms

A Phase 3 study testing Direct Oral Anticoagulants and Low-dose aspirin in people with Polycythemia Vera and Essential Thrombocythemia, run by University Hospital, Brest at 42 sites in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Philadelphia-negative myeloproliferative neoplasms (MPN) are frequent and chronic myeloid malignancies including Polycythemia Vera (PV), essential thrombocythemia (ET), Primary Myelofibrosis (PMF) and Prefibrotic myelofibrosis (PreMF). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Direct Oral Anticoagulants and Low-dose aspirin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,308 participants
Where
42 sitesFrance
Study dates
13 Jul 2022to 13 Jul 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with diagnosis of PV or ET or PreMF according to WHO or BSCH criteria (bone marrow biopsy not compulsory).
  • Patients with JAK2V617F mutation (threshold allele burden > 1%).
  • Patients considered as "high-risk" patients:
  • based on age (> 60-year-old)
  • based on thrombotic history (compatible with antithrombotic randomization) but aged ≥ 18-year-old.
  • Length of time from MPN diagnostic to inclusion will not exceed 12 months.

Who cannot join

  • Contra-indication to aspirin or DOAC due to allergic situation or recent history of major bleeding.
  • Formal indication of treatment with aspirin or DOAC (thus precluding randomization).
  • Inability to give informed consent.
  • Patients under curatorship/guardianship
  • Concomitant use of a strong inhibitor or inducer of CYP3A4 (like ruxolitinib).
  • Chronic liver disease or chronic hepatitis.
Show all 11Show fewer
  • Renal insufficiency with creatinine <30 ml/mn on Cockcroft and Gault Formula
  • Patient considered at high-risk of bleeding: patients with current or recent major or clinical relevant non major bleeding gastrointestinal or cerebral bleedings
  • Planned pregnancy within 24 months
  • No appropriate contraception (estrogen contraception or no contraception) in women of childbearing age or breastfeeding woman
  • PS>2 or life expectancy <12 months.

Trial locations and contacts

42 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Jean-Christophe IANOTTO, Pr contact

+33298223421

jean-christophe.ianotto@chu-brest.fr

42 sites in 1 country

France42 sites, 42 recruiting

  • CHU d'Angers

    Angers, 49933

    Corentin ORVAIN, PH, +33615270461, corentin.orvain@chu-angers.fr

    Corentin ORVAIN, PH

    Recruiting

  • CH d'Annecy

    Annecy, 74374

    Anne PARRY, PH, +33450635101, aparry@ch-annecygenevois.fr

    Anne PARRY, PH

    Not yet recruiting

  • CH d'Argenteuil

    Argenteuil, 95100

    Annalisa ANDREOLI, PH, annalisa.andreoli@ch-argenteuil.fr

    Annalisa ANDREOLI, PH

    Not yet recruiting

  • CH d'Avignon

    Avignon, 84000

    Borhane SLAMA, PH, bslama@ch-avignon.fr

    Borhane SLAMA, PH

    Recruiting

  • CH de la Côte Basque Bayonne

    Bayonne, 64100

    Frédéric BAUDUER, PH, frederic.bauduer@u-bordeaux.fr

    Frédéric BAUDUER, PH

    Not yet recruiting

  • CH de Béziers

    Béziers, 34500

    Alain Radwan SAAD, PH, alain.saad@ch-beziers.fr

    Alain Radwan SAAD, PH

    Not yet recruiting

  • CHU Bordeaux

    Bordeaux, 33604

    Clémence MEDIAVILLA, PH, clemence.mediavilla@chu-bordeaux.fr

    Clémence MEDIAVILLA, PH

    Recruiting

  • CHU Brest

    Brest, 29609

    Jean-Christophe Ianotto, PUPH, jean-christophe.ianotto@chu-brest.fr

    Jean-Christophe Ianotto, PUPH

    Recruiting

  • Hôpital privé Cesson-Sévigné

    Cesson-Sévigné, 35510

    Benoît BAREAU, PH, benoit.bareau@gmail.com

    Benoît BAREAU, PH

    Not yet recruiting

  • CHU de Clermont-Ferrand

    Clermont-Ferrand, 63003

    Benoît DE RENZIS, PH, bderenzis@chu-clermontferrand.fr

    Benoît DE RENZIS, PH

    Not yet recruiting

  • Hôpital Henri Mondor (APHP)

    Créteil, 94010

    Lydia ROY, PH, lydia.roy@aphp.fr

    Lydia ROY, PH

    Recruiting

  • CHU Grenoble Alpes

    Grenoble, 38043

    Mathieu MEUNIER, PH, mmeunier2@chu-grenoble.fr

    Mathieu MEUNIER, PH

    Recruiting

  • CHD Vendée La Roche Sur Yon

    La Roche-sur-Yon, 85925

    Bruno VILLEMAGNE, PH, bruno.villemagne@chd-vendee.fr

    Bruno VILLEMAGNE, PH

    Recruiting

  • CHU Le Havre

    Le Havre, 76083

    Pierre LEBRETON, PH, pierre.lebreton@ch-havre.fr

    Pierre LEBRETON, PH

    Not yet recruiting

  • CH Le Mans

    Le Mans, 72000

    Kamel LARIBI, PH, klaribi@ch-lemans.fr

    Kamel LARIBI, PH

    Not yet recruiting

  • CH Libourne

    Libourne, 33500

    Diane LARA, PH, Diane.Lara@ch-libourne.fr

    Diane LARA, PH

    Not yet recruiting

  • CHU de Limoges - Hôpital Dupuytren

    Limoges

    Amélie PENOT, PH, amelie.penot@chu-limoges.fr

    Amélie PENOT, PH

    Recruiting

  • Centre Léon Bérard Lyon

    Lyon, 69000

    Franck-Emmanuel NICOLINI, PH, franc-emmanuel.nicolini@lyon-unicancer.fr

    Franck-Emmanuel NICOLINI, PH

    Not yet recruiting

  • CHU de Montpellier

    Montpellier, 34295

    Franciane PAUL, PH, f-paul@chu-montpellier.fr

    Franciane PAUL, PH

    Not yet recruiting

  • CH de Morlaix

    Morlaix, 29600

    Christophe NICOL, PH, cnicol@ch-morlaix.fr

    Christophe NICOL, PH

    Recruiting

  • CHU de Nancy

    Nancy, 54511

    Dana RANTA, PH, d.ranta@chu-nancy.fr

    Dana RANTA, PH

    Recruiting

  • CHU de Nantes - Hôtel-Dieu

    Nantes, 44093

    Viviane DUBRUILLE, PH, viviane.dubruille@chu-nantes.fr

    Viviane DUBRUILLE, PH

    Not yet recruiting

  • Hôpital Privé du Confluent Nantes

    Nantes, 44202

    Katell LE DU, PH, dr.ledu@groupeconfluent.fr

    Katell LE DU, PH

    Not yet recruiting

  • CHR d'Orléans

    Orléans, 45100

    Marlène OCHMANN, PH, marlene.ochmann@chr-orleans.fr

    Marlène OCHMANN, PH

    Recruiting

  • Hôpital St-Louis (APHP)

    Paris, 75010

    Jean-Jacques KILADJIAN, PUPH, jean-jacques.kiladjian@aphp.fr

    Jean-Jacques KILADJIAN, PUPH

    Recruiting

  • Hôpital Cochin (APHP)

    Paris, 75679

    Michaela FONTENAY, PH, michaela.fontenay@aphp.fr

    Michaela FONTENAY, PH

    Not yet recruiting

  • CH de Périgueux

    Périgueux, 24019

    Claire CALMETTE, PH, claire.calmettes@ch-perigueux.fr

    Claire CALMETTE, PH

    Recruiting

  • CH de Perpignan

    Perpignan, 66000

    Virginie ROLAND, PH, virginie.roland@ch-perpignan.fr

    Virginie ROLAND, PH

    Not yet recruiting

  • CHIC de Quimper

    Quimper, 29107

    Lénaïg LE CLECH, PH, l.leclech@ch-cornouaille.fr

    Lénaïg LE CLECH, PH

    Recruiting

  • CHU de Rennes

    Rennes, 35033

    Marc BERNARD, PH, marc.nernard@chu-rennes.fr

    Marc BERNARD, PH

    Not yet recruiting

  • CH de Rochefort

    Rochefort, 17300

    Guillaume DENIS, PH, guillaume.denis@ch-rochefort.fr

    Guillaume DENIS, PH

    Not yet recruiting

  • CH de Roubaix

    Roubaix, 59100

    Mathieu WEMEAU, PH, mathieu.wemeau@chu-roubaix.fr

    Mathieu WEMEAU, PH

    Recruiting

  • Centre Henri Becquerel de Rouen

    Rouen, 76038

    Fabrice JARDIN, PH, fabrice.jardin@chb.unicancer.fr

    Fabrice JARDIN, PH

    Recruiting

  • CHU La Réunion - Site Nord Félix GUYON

    Saint-Denis, 97405

    Stéphane VANDERBECKEN, PH, stephane.vanderbecken@chu-reunion.fr

    Stéphane VANDERBECKEN

    Not yet recruiting

  • CHU La Réunion - Site Sud

    Saint-Pierre, 97410

    Raphaëlle DINE, PH, raphaelle.dine@chu-reunion.fr

    Raphaëlle DINE, PH

    Not yet recruiting

  • Institut de Cancérologie Lucien Neuwirth St-Priest-en-Jarez

    Saint-Priest-en-Jarez, 42271

    Emilie CHALAYER, PH, emilie.chalayer@icloire.fr

    Emilie CHALAYER, PH

    Recruiting

  • Clinique Sainte Anne Strasbourg

    Strasbourg, 92210

    Anaïse BLOUET, PH, ablouet@solcrr.org

    Anaïse BLOUET, PH

    Not yet recruiting

  • CHU de Tours

    Tours, 37044

    Antoine MACHET, PH, a.machet@chu-tours.fr

    Antoine MACHET, PH

    Recruiting

  • CH Bretagne Atlantique Vannes

    Vannes, 56017

    Mélanie MERCIER, PH, melanie.mercier@ch-bretagne-atlantique.fr

    Mélanie MERCIER, PH

    Recruiting

  • CH de Versailles

    Versailles, 78150

    Juliette LAMBERT, PH, jlambert@ch-versailles.fr

    Juliette LAMBERT, PH

    Not yet recruiting

  • CH Paul-Brousse (APHP)

    Villejuif, 94800

    Laurence LE GROS, PH, laurence.legros@aphp.fr

    Laurence LE GROS, PH

    Not yet recruiting

  • Médipôle Hôpital Mutualiste Villeurbanne

    Villeurbanne, 69616

    Mathias BREHON, PH, m.brehon@resamut.fr

    Mathias BREHON, PH

    Recruiting

Other trials in France

About this study

Philadelphia-negative myeloproliferative neoplasms (MPN) are frequent and chronic myeloid malignancies including Polycythemia Vera (PV), essential thrombocythemia (ET), Primary Myelofibrosis (PMF) and Prefibrotic myelofibrosis (PreMF). These MPNs are caused by the acquisition of mutations affecting activation/proliferation pathways in hematopoietic stem cells. The principal mutations are JAK2V617F, calreticulin (CALR exon 9) and MPL W515. ET or MFP/PreMF patients who do not carry one of these three mutations are declared as triple-negative (3NEG) cases even if they are real MPN cases.

These diseases are at high risk of thrombo-embolic complications and with high morbidity/mortality. This risk varies from 4 to 30% depending on MPN subtype and mutational status.

Read more

In terms of therapy, all patients with MPNs should also take daily low-dose aspirin (LDA) as first antithrombotic drug, which is particularly efficient to reduce arterial but not venous events.

Despite the association of a cytoreductive drug and LDA, thromboses still occur in 5-8% patients/year.

All these situations have been explored in biological or clinical assays. All of them could increase the bleeding risk. We should look at different ways to reduce the thrombotic incidence: Direct Oral Anticoagulants (DOAC)? In the general population, in medical or surgical contexts, DOACs have demonstrated their efficiency to prevent or cure most of the venous or arterial thrombotic events.

At the present time, DOAC can be used in cancer populations according to International Society on Thrombosis and Haemostasis (ISTH) recommendations, except in patients with cancer at high bleeding risk (gastro-intestinal or genito-urinary cancers). Unfortunately, in trials evaluating DOAC in cancer patients, most patients have solid rather than hematologic cancers (generally less than 10% of the patients, mostly lymphoma or myeloma).

In cancer patients, DOAC are also highly efficient to reduce the incidence of thrombosis (-30 to 60%), but patients are exposed to a higher hemorrhagic risk, especially in digestive cancer patients.

In the cancer population, pathophysiology of both thrombotic and hemorrhagic events may be quite different between solid cancers and MPN. If MPN patients are also considered to be cancer patients in many countries, the pathophysiology of thrombosis is quite specific (hyperviscosity, platelet abnormalities, clonality, specific cytokines…) and they are exposed to a lower risk of digestive hemorrhages. It is thus difficult to extend findings from the "general cancer population" to MPN patients.

Unfortunately, only scarce, retrospective data regarding the use of DOAC in MPNs are available data.

We were the first to publish a "real-life" study about the use, the impact, and the risks in this population. In this local retrospective study, 25 patients with MPN were treated with DOAC for a median time of 2.1 years. We observed only one thrombosis (4%) and three major hemorrhages (12%, after trauma or unprepared surgery). Furthermore, we have compared the benefit/risk balance compared to patients treated with LDA without difference.

With the increasing evidences of efficacy and tolerance of DOAC in large cohorts of patients including cancer patients, with their proven efficacy on prevention of both arterial and venous thrombotic events and because of the absence of prospective trial using these drugs in MPN patients, we propose to study their potential benefit as primary thrombotic prevention in MPN.

Being tested
Direct Oral Anticoagulants, Low-dose aspirin
Keywords
Venous ThromboEmbolism, Arterial Thrombosis, Hemorrhage
Medical subject headings
Polycythemia Vera, Thrombocythemia, Essential, Primary Myelofibrosis, Venous Thromboembolism, Hemorrhage

What participants receive

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

  • Direct Oral AnticoagulantsDrug

    Patients randomized to receive DOAC, at the choice of the investigator: Apixaban 2.5 mg both in day or Rivaroxaban 10 mg once daily.

  • Low-dose aspirinDrug

    Patients allocated to receive LDA: Aspirin 100 mg OD once daily.

Study groups in NCT05198960
Study groupRoleWhat they receive
Experimental groupExperimentalPatients randomized to receive Direct Oral Anticoagulants, at the choice of the investigator Apixaban 2.5 mg both in day or Rivaroxaban 10 mg one per day, at the choice of the investigator
Receives: Drug: Direct Oral Anticoagulants
Control groupActive comparatorPatients randomized to receive Low-Dose Aspirin Aspirin 100 mg one per day
Receives: Drug: Low-dose aspirin

What is being measured

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

  1. Time to occurrence of arterial or venous thromboembolic events.

    Nb and type of thrombotic events during the FU

    Measured: Time to occurrence up to 24 months of patient follow-up

Secondary outcomes (11)

  1. Time to occurrence of major and clinically relevant non-major bleedings as defined by International Society on Thrombosis and Haemostasis

    Nb and type of new hemorrhagic events

    Measured: Time to occurrence up to 24 months of patient follow-up

  2. Time to occurrence of arterial thromboembolic events.

    Nb and type of new arterial events

    Measured: Time to occurrence up to 24 months of patient follow-up

  3. Time to occurrence of venous thromboembolic

    Nb and type of new venous events

    Measured: Time to occurrence up to 24 months of patient follow-up

  4. Time to occurrence of thromboembolic and bleeding events according to the cytoreductive associated drugs

    Nb and type of new thromboembolic and hemorrhage events

    Measured: Time to occurrence up to 24 months of patient follow-up

  5. Time to occurrence of serious adverse events others than thromboses and hemorrhages hemorrhages

    Nb, type and grade of adverse events observed

    Measured: Time to occurrence up to 24 months of patient follow-up

  6. Overall survival and event-free survival

    Time to last news and time to first event

    Measured: 24 months

  7. Therapeutic adherence

    Therapeutic adherence by Girerd auto-questionnaire

    Measured: 24 months

  8. Occurrence of atrial fibrillation episode (time to occurrence).

    Nb and timing of atrial fibrillation event

    Measured: 24 months

  9. Evaluation of Quality of life under antithrombotic drugs

    Evaluation of QoL by the use of MPN-SAF Quality of life

    Measured: 24 months

  10. Evaluation of costs and incremental cost utility ratio of low-dose DOAC compared to low-dose aspirin

    Evaluation of benefits/costs under antithrombotic drugs

    Measured: 24 months

  11. Evaluation of Quality of life under antithrombotic drugs

    Evaluation of QoL by the use of EQ-5D-5L Quality of life

    Measured: 24 months

Timeline

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

  1. First posted20 Jan 2022
  2. Study start13 Jul 2022
  3. Primary completion13 Jul 2027 (estimated)
  4. Study completion13 Jul 2027 (estimated)

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 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
AVAJAK is an academic multicenter phase 3 prospective, randomized, and open label trial. \> Randomization of the patients: Patients corresponding to inclusion criteria will be randomized based on a 1:1 distribution. * Experimental group (Patients allocated to receive low-dose DOAC, at the choice of the investigator) * Apixaban 2.5 mg BID or * Rivaroxaban 10 mg OD, at the choice of the investigator. * Control group (Patients allocated to receive LDA) \- Aspirin 100 mg OD Dispensation of treatments every 6 months for 24 months * Stratification: * First stratification will be done by center * Second stratification will be done by pathology (PV/ET/ PreMF) * No stratification will be made based on DOAC drugs.
Masking
None (open label)
Enrolment
1,308 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05198960
Sponsor's protocol ID
29BRC20.0263 (AVAJAK)
Acronym
AVAJAK
Status last verified
Mar 2026
First submitted
9 Nov 2021
Last updated
20 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: All collected data that underlie results in a publication

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Direct Oral Anticoagulants and Low-dose aspirin in people with Polycythemia Vera and Essential Thrombocythemia, run by University Hospital, Brest at 42 sites in France.

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 6 inclusion and 11 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: looking for participants now, as of the sponsor's last update on 20 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 42 sites in France. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Contact Jean-Christophe IANOTTO, Pr (+33298223421, jean-christophe.ianotto@chu-brest.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to occurrence of arterial or venous thromboembolic events. (time frame: Time to occurrence up to 24 months of patient follow-up). 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 NCT05198960.

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 20 Mar 2026.

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