Assessing Feasibility of Thromboprophylaxis With Apixaban in JAK2-positive Myeloproliferative Neoplasm Patients

NCT04243122 | Completed Phase 2 DMC

• 1 other identifier: AIRPORT-MPN-001
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Myeloproliferative Neoplasm (MPN); Essential Thrombocythemia (ET); JAK2 Mutation; Polycythemia Vera (PV); Primary Myelofibrosis; Venous Thromboembolism (VTE)

Outcome Measures

Primary Outcomes (6)

• Average monthly subject recruitment rate of all study sites during a 6-month recruitment period

  For the duration of study enrollment period: 6 months

• 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

  For the duration of study enrollment period: 6 months

• Study Feasibility 1: Feasibility of recruitment

  Feasibility of recruitment efforts will be determined by the proportion of patients contacted for screening versus those who are consented

  For the duration of study enrollment period: 6 months

• Study Feasibility 2: Feasibility of enrollment

  Feasibility of enrollment will be determined by the proportion of patients consented vs those were enrolled and randomized

  For the duration of study enrollment period: 6 months

• Study Feasibility 3: Patient retention rate

  This will be defined as the proportion of patients who started study intervention versus those who completed each of the study follow-up visits.

  For the duration of the study follow-up period: 7 months

• 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.

  For the duration of the study follow-up period: 7 months

Secondary Outcomes (7)

• 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

  For the duration of the study follow-up period: 7 months

• Study visit compliance as assessed by the number of study visits (in person and/or phone call) completed

  For the duration of the study follow-up period: 7 months

• Percentage of incident and prevalent cases included in the study

  For the duration of study enrollment period: 6 months

• Rate of combined arterial and venous thrombotic events (MI, stroke, transient ischemic attack, peripheral arterial thrombosis, VTE)

  For the duration of the study follow-up period: 7 months

• Rate of major bleeding as per the International Society of Thrombosis and Hemostasis definitions

  For the duration of the study follow-up period: 7 months

Study Arms (2)

Aspirin and cytoreductive therapy (if applicable)

ACTIVE COMPARATOR

Patients who are randomized to this group will take a low-dose aspirin 81mg pill once per day (standard-of-care) for at least 6 months along with cytoreductive therapy, if applicable. Patients will then be treated and followed up as per standard of care at the discretion of his or her treating physician after the completion of the study.

Drug: Aspirin 81 mg

Apixaban and cytoreductive therapy (if applicable)

EXPERIMENTAL

Patients who are randomized to this group will receive apixaban 2.5mg twice daily for at least 6 months along with standard intervention, cytoreductive therapy, if applicable. Patients will then be treated and followed up as per standard of care at the discretion of their treating physician after the completion of the study.

Drug: Apixaban 2.5 MG Oral Tablet [ELIQUIS]

Interventions

Apixaban 2.5 MG Oral Tablet [ELIQUIS] DRUG

2.5mg twice per day for 6 months Then treated \& followed up as per standard of care

Also known as: Eliquis

Apixaban and cytoreductive therapy (if applicable)

Aspirin 81 mg DRUG

81mg once per day for 6 months Then treated \& followed up as per standard of care

Also known as: Acetylsalicylic acid

Aspirin and cytoreductive therapy (if applicable)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network: collaborator
• the Association médicale universitaire de l'Hôpital Montfort (AMUHM): collaborator
• Canadian Hematology Society: collaborator

Study Sites (1)

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

MeSH Terms

Conditions

Myeloproliferative Disorders; Thrombocythemia, Essential; Polycythemia Vera; Primary Myelofibrosis; Venous Thromboembolism

Interventions

apixaban; Tablets; Aspirin

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Aurelien Delluc, MD, PhD

  The Ottawa Hospital

  PRINCIPAL INVESTIGATOR

• Miriam Kimpton, MD

  The Ottawa Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2020
• First Posted: January 28, 2020
• Study Start: February 17, 2021
• Primary Completion: October 31, 2023
• Study Completion: May 3, 2024
• Last Updated: May 29, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)