Hydroxyurea Versus Aspirin and Hydroxyurea in Essential Thrombocythemia (FAST)

Assistance Publique - Hôpitaux de Paris

Status and phase: Unknown; Phase 3

Conditions: Essential Thrombocythemia; MPN

Treatments: Drug: Hydroxyurea treatment (HU); Other: Usual treatment by aspirin 100 mg/d in the active comparator arm; Other: Aspirin therapy interruption; Other: No interruption of aspirin in the Observational arm

Study type: Interventional

Funder types: Other

Identifiers

NCT02611973

P140933

Details and patient eligibility

About

The hypothesis is that efficient prevention of thrombosis with aspirin at diagnosis becomes less useful once patients have achieved a hematologic response (HR) (modified by amendment 1/03/2017) and/or that this benefit is hampered by an increased hemorrhagic risk especially in elderly patients.

Hence, investigator propose a prospective randomized study to assess the benefit / risk ratio of aspirin maintenance in high risk Essential thrombocythemia (ET) patients, in hematological response (modified by amendment 1/03/2017) on Hydroxyurea.

Full description

ET is a myeloproliferative neoplasm (MPN) characterized by a high platelet level. Increased occurrence of thrombosis and hemorrhages are the main complications in ET. In this regard, the key factors defining high risk ET include age over 60 years, past history of thrombosis, platelet > 1500 109/L and to a lesser degree cardiovascular risk factors. These criteria currently serve as therapeutic guidelines for the use of cytoreductive therapy, with hydroxyurea (HU) being the treatment of choice in the first line setting.

The use of antiplatelet agent i.e. low-dose aspirin is also generally recommended. However, the benefit of aspirin has never been formally demonstrated in ET. Only indirect evidence come from the ECLAP study that enrolled patients with polycythemia vera (PV). Of note in the ECLAP study, the efficacy of aspirin was assessed only at diagnosis but not correlated thereafter with the hematological response on cytoreductive therapy.

In general non-MPN population studies, primary prophylaxis with aspirin has been associated with a risk reduction of major vascular events, but an increased risk of hemorrhage, especially considering age and prior gastrointestinal history. In a recent retrospective study, the combination of aspirin and cytoreduction was reported to prevent thrombosis but concomitantly increase the bleeding risk when compared to HU alone , especially in patients older than 60 years, thus questioning the benefits of long term use of aspirin therapy. These data raise the question of the actual benefit of aspirin maintenance, once patients have been efficiently treated with cytoreductive therapy.

Hence, investigator propose a prospective randomized study to assess the benefit / risk ratio of aspirin maintenance in high risk ET patients, in hematological response (modified by amendment 1/03/2017) on Hydroxyurea. Patients for which Aspirin interruption will not be possible because of extra-ET indications will be enrolled in the control observational arm.

Enrollment: 2,250 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• > 18 years and older (modified by amendment 01/03/2017)

• Contraception considered effective by the investigator: for women of childbearing and for men whose partner is likely to procreate (added by amendment 01/03/2017)

  • Diagnosis of ET performed within the last 10 years (modified by amendment 01/03/2017) : with or without Janus kinase 2V617F (JAK2V617F) mutation according to the WHO 2008 criteria (TEFFERI,2007)
  • ET patients currently treated with hydroxyurea in first line, who have achieved a complete or partial hematologic response according to the ELN 2009 (BAROSI, 2009) modified (at least three month apart and at inclusion) (modified by amendment 01/03/2017)
  • Signed Written Informed Consent
  • Health insurance coverage.

Exclusion criteria

• Other myeloproliferative disorder than ET.

• Contra-indication to hydroxyurea.

• Other uncontrolled malignancies at the time of diagnosis or inclusion.

• History of haemostasis perturbation not related to ET, associated with a significant risk of hemorrhage or thrombosis (modified by amendment 01/03/2017)

  -.• Pregnancy or breastfeeding (added by amendment 01/03/2017)

• Inability to freely provide consent through judiciary or administrative condition.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,250 participants in 3 patient groups

HU without aspirin

Experimental group

Treatment:

Other: Aspirin therapy interruption

Drug: Hydroxyurea treatment (HU)

HU + aspirin maintenance

Active Comparator group

Treatment:

Other: Usual treatment by aspirin 100 mg/d in the active comparator arm

Drug: Hydroxyurea treatment (HU)

HU + AAG

Other group

Description:

Observational arm

Treatment:

Other: No interruption of aspirin in the Observational arm

Drug: Hydroxyurea treatment (HU)