Clinical trial NCT04243122: Assessing Feasibility of Thromboprophylaxis With Apixaban in JAK2-positive Myeloproliferative Neoplasm Patients
Official title: A Phase 2 Pilot Randomized Controlled Trial Assessing Feasibility of Thromboprophylaxis With Apixaban in JAK2-positive Myeloproliferative Neoplasm Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myeloproliferative Neoplasm (MPN)
Essential Thrombocythemia (ET)
JAK2 Mutation
Polycythemia Vera (PV)
Primary Myelofibrosis
Venous Thromboembolism (VTE)
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network
name: the Association médicale universitaire de l'Hôpital Montfort (AMUHM)
name: Canadian Hematology Society
First posted: 2020-01-28
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Myeloproliferative neoplasms (MPNs) are blood disorders that occur when the body makes too many white or red blood cells, or platelets. This overproduction of blood cells in the bone marrow can create problems for blood flow and lead to various symptoms. One of the major problems is the formation of blood clots. These may form in the veins of a patient's legs or arms where they cause leg or arm pain, swelling or difficulty walking. These clots may travel to the lung and then cause chest pain, shortness of breath and sometimes death. Blood clots can also lead to poor or no blood flow to one's heart, brain, or other organs, causing damages that cannot be easily or ever repaired, such as stroke or heart attack.

Patients diagnosed with certain types of MPN are associated with a higher risk of developing blood clots and related complications. For this reason, MPN patients are usually treated with low-dose aspirin, a common drug used for blood clot prevention, on long-term basis to prevent the formation of blood clots and other complications. However, recent studies also show that the risk of blood clots remains elevated in MPN patients treated with aspirin, and there may not be improvement or reduction in fatal or other events that are associated with blood clots. In addition, since this medical condition is rare, so there's a lack of studies done with high quality results to help physicians decide the best treatment plan for these patients.

The study drug, apixaban, is a new type of orally-taken blood thinner that has been shown to be effective and safe for prevention and treatment of blood clots in various patient populations. The investigators will evaluate whether apixaban is safer and/or better at preventing blood clots and other complications in MPN patients compared to aspirin.


Eligibility criteria: Inclusion Criteria:

1. Male or female subjects aged 18 years or older,
2. Confirmed diagnosis of PV, JAK2ET or JAK2 pre-fibrotic MF, per local clinical definitions
3. Able and willing to comply with study procedures and follow-up examinations contained within the written consent form

Exclusion Criteria:

1. Known allergy to apixaban or aspirin,
2. Another need for anticoagulation or specific anti-platelet therapy,
3. Contraindication to thromboprophylaxis (which would specifically include but not be limited to platelets less than 50x10\^9/L and acquired Von Willebrand disease),
4. Current pregnancy or breast-feeding,
5. Renal dysfunction (Creatine Clearance \<25 mL/min),
6. Known liver disease
7. Currently on any medication with a known interaction to apixaban
8. Unwilling to use an effective means of contraception for women of childbearing potential
9. Overtly fibrotic myelofibrosis
10. Myelodysplastic/myeloproliferative neoplasms

Primary outcomes:
measure: Average monthly subject recruitment rate of all study sites during a 6-month recruitment period
timeFrame: For the duration of study enrollment period: 6 months
measure: Number of JAK2MPN patients recruited in 6 months in comparison to a target recruitment total of 39 prevalent cases and 5 incident cases at minimum
timeFrame: For the duration of study enrollment period: 6 months
measure: Study Feasibility 1: Feasibility of recruitment
timeFrame: For the duration of study enrollment period: 6 months
measure: Study Feasibility 2: Feasibility of enrollment
timeFrame: For the duration of study enrollment period: 6 months
measure: Study Feasibility 3: Patient retention rate
timeFrame: For the duration of the study follow-up period: 7 months
measure: Quality of life on apixaban and aspirin will be measured through the use of the RAND 36-Item Health Survey (SF-36), with scores being transformed into a 0-100 scale where the higher the score the less disability.
timeFrame: For the duration of the study follow-up period: 7 months
Secondary outcomes:
measure: Study drug compliance as assessed by the proportion of study drug prescribed to the patient versus the actual amount study drug taken by the patient
timeFrame: For the duration of the study follow-up period: 7 months
measure: Study visit compliance as assessed by the number of study visits (in person and/or phone call) completed
timeFrame: For the duration of the study follow-up period: 7 months
measure: Percentage of incident and prevalent cases included in the study
timeFrame: For the duration of study enrollment period: 6 months
measure: Rate of combined arterial and venous thrombotic events (MI, stroke, transient ischemic attack, peripheral arterial thrombosis, VTE)
timeFrame: For the duration of the study follow-up period: 7 months
measure: Rate of major bleeding as per the International Society of Thrombosis and Hemostasis definitions
timeFrame: For the duration of the study follow-up period: 7 months
measure: Rate of non-major clinically relevant bleeding as per the International Society of Thrombosis and Hemostasis definitions
timeFrame: For the duration of the study follow-up period: 7 months
measure: Rate of all-cause mortality
timeFrame: For the duration of the study follow-up period: 7 months
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
Study officials:
affiliation: The Ottawa Hospital
name: Aurelien Delluc, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Ottawa Hospital
name: Miriam Kimpton, MD
role: PRINCIPAL_INVESTIGATOR
References: