Apixaban/rivaroxaban Versus Aspirin for primary prevention of thrombo-embolic complications in JAK2V617F-positive myeloproliferative neoplasms

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Regional Et Universitaire De Brest

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2024-08-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515362-13-00

EudraCT number

2020-004652-15

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To demonstrate that low-dose DOAC is more effective than LDA in the primary prevention of arterial or venous thrombosis in JAK2V617F-positive high-risk MPN patients

Secondary objectives 12

1. To compare the risk of antithrombotic-related bleeding in patients receiving low-dose DOAC as compared to those receiving LDA
2. To compare the efficacy of low-DOAC versus LDA on the prevention of arterial thrombosis
3. To compare the efficacy of low-DOAC versus LDA on the prevention of venous thrombosis
4. To compare the efficacy and toxicity of low-DOAC versus LDA in terms of MPN subtypes
5. To compare the efficacy and toxicity of low-DOAC versus LDA in terms of cytoreductive associated drugs
6. To evaluate the risk of other adverse events
7. To evaluate the benefit of prevention by low-dose DOAC versus LDA in terms of overall survival and event free survival with venous and arterial thrombosis and clinically significant bleeding complications considered as events
8. To evaluate the non cardiovascular and cardiovascular deaths for patients treated with low-dose DOAC versus LDA
9. To compare treatment compliance to antithrombotic drugs patients treated with low-dose DOAC versus LDA
10. To compare the incidence of atrial fibrillation in the low-dose DOAC group versus the LDA group
11. To compare the quality of life of patients treated with low-dose DOAC versus LDA
12. To provide economic evaluation of the use of low-dose DOACs for thrombosis prevention

Conditions and MedDRA coding

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

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Patients with diagnosis of Polycythemia Vera or Essential Thrombocythemia or Prefibrotic myelofibrosis according to WHO or BSCH criteria (bone marrow biopsy not compulsory).
2. Patients with JAK2V617F mutation (threshold allele burden > 1%).
3. Patients considered as “high-risk” patients: - 1°) based on age (> 60-year-old) - 2°) based on thrombotic history (compatible with antithrombotic randomization) but aged ≥ 18-year-old
4. Length of time from MPN diagnostic to inclusion will not exceed 12 months

Exclusion criteria 11

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to occurrence of arterial or venous thromboembolic events

Secondary endpoints 12

1. Time to occurrence of major and clinically relevant non-major bleedings as defined by ISTH
2. Time to occurrence of arterial thromboembolic events
3. Time to occurrence of venous thromboembolic events
4. Time to occurrence of thromboembolic and bleeding events according to PV or ET or PreMF status
5. Time to occurrence of thromboembolic and bleeding events according to the cytoreductive associated drugs
6. Time to occurrence of serious adverse events others than thromboses and hemorrhages
7. Occurrence of atrial fibrillation episodes (time to occurrence)
8. Overall survival and event free survival (events defined above) at 24 months
9. Adjudicated mortality (non-cardiovascular and cardiovascular), time to occurence
10. Therapeutic adherence will be studied (Girerd auto-questionnaire) during the study treatment period of 24 months
11. Quality of life will be studied (EQ-5D-5L and MPN-SAF-TSS auto-questionnaire) during the study treatment period of 24 months
12. Evaluation of costs and incremental cost utility ratio (cost per QALY) of low-dose DOAC compared to LDA

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Regional Et Universitaire De Brest

Sponsor organisation

Centre Hospitalier Regional Et Universitaire De Brest

Address

5 Avenue Marechal Foch, Bp 824 Bp 824

City

Brest Cedex 2

Postcode

29609

Country

France

Scientific contact point

Organisation

Centre Hospitalier Regional Et Universitaire De Brest

Contact name

Pr Jean-Christophe IANOTTO

Public contact point

Organisation

Centre Hospitalier Regional Et Universitaire De Brest

Contact name

Pr Jean-Christophe IANOTTO

Locations

1 EU/EEA country · 44 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications