Treatment of Polycythaemia Vera and Essential Thrombocythaemia: Influence on the Clot Structure

NCT02912884 | Completed

• 1 other identifier: CCER 2016-00950
• Study Type: observational
• Target: 80
• Locations: 2 countries
• Sites: 2

Brief Summary

Myeloproliferative neoplasms (MPN) such as Polycythemia Vera (PV) and, Essential Thrombocythaemia (ET) are rare clonal myeloid neoplasms associated with an increased risk of both venous and arterial thrombosis. Thrombotic complications are the main determinant of morbidity and in a less extend mortality. Routine haemostasis analysis (TP, aPTT) are usually normal and are useless to demonstrate a hypercoagulable state. However, previous evidence suggests that global coagulation tests such as thrombin generation or thromboelastometry are able to detect signs of procoagulant imbalance in MPN. Similarly, current data seems to demonstrate that fibrin clot properties (clot permeability, turbidimetry, clot lysis time) properties is altered suggesting an hypercoagulable state. Goals of PV and ET treatments are to control blood count to reduce the risk of thrombotic events. Moreover, new drugs such as Janus Kinase Inhibitors (JAKi) were recently licensed for PV and are under investigations on clinical trial for ET. It is currently unknown if treatments that were used for ET and PV, and especially JAKi are able to modify the hypercoagulable state that is observed in those diseases, and if there is difference between drugs. To evaluate impact of MPN treatment on prothrombotic haemostatic profile, we propose to evaluate global coagulation and fibrin clot properties in MPN, depending on the treatment.

Conditions

Polycythemia Vera; Thrombocythemia, Essential

Outcome Measures

Primary Outcomes (3)

• Fibrin polymerization; lag-time (in seconds)

  Fibrin polymerization will be assessed by turbidity assay on plasma. Fibrin polymerization will be monitored at 340 nm after incubation with human thrombin and CaCl2. Results will report lag-time (seconds).

  At time of inclusion

• Fibrin polymerization; maximal absorbance

  Fibrin polymerization will be assessed by turbidity assay on plasma. Fibrin polymerization will be monitored at 340 nm after incubation with human thrombin and CaCl2. Results will report maximal absorbance.

  At time of inclusion

• Clot lysis time (in minutes)

  Fibrinolysis will be assessed by turbidity assay on plasma. Fibrinolysis will be monitored by adding tissue plasminogen activator (tPA). Results will report clot lysis time (minutes)

  At time of inclusion

Secondary Outcomes (5)

• Clot permeation; permeation coefficient

  At time of inclusion

• Quantitative parameters of thrombin generation test (TGT); endogenous thrombin potential (nM*minutes)

  At time of inclusion

• Quantitative parameters of thrombin generation test (TGT); peak (nM)

  At time of inclusion

• Quantitative parameters of thrombin generation test (TGT); time to peak (minutes)

  At time of inclusion

• Fibrin density by laser scanner confocal microscopy (number per 100 μm)

  At time of inclusion

Study Arms (2)

PV

Patients with a diagnosis of polycythaemia vera.

Drug: No cytoreductive vs cytoreductive drugs

ET

Patients with a diagnosis of essential thrombocythaemia.

Drug: No cytoreductive vs cytoreductive drugs

Interventions

No cytoreductive vs cytoreductive drugs DRUG

No cytoreductive treatment vs cytoreductive drugs (hydroxycarbamide, alpha-interferon, ruxolitinib).

ET; PV

Eligibility Criteria

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

Study Population

Screening for participation for MPN patients will occur at the outpatient clinic of the division of Haematology at the Geneva University Hospitals (Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland) and at the outpatient clinic of the division of Haematology at Guy's Hospitals (Great Maze Pond, London SE1 9RT, United Kingdom).

You may qualify if:

• All men and women, older than 18 years, with a diagnosis of PV or ET (primary or secondary) according to the 2008 World Health Organization (WHO) classification.

You may not qualify if:

• Lack of participant's consent;
• Concomitant treatment with anticoagulant drugs (anti-vitamin K, heparin or direct oral anticoagulant drugs);
• Active cancer other than non-melanoma skin cancer (defined as cancer diagnosis \<5 years or treatment \<2 years);
• Recent infection (\<30d);
• Recent surgery (\<30d);
• Recent hospitalization (\<30d);
• Recent thromboembolic or cardiovascular event (\<3m).

Sponsors & Collaborators

• Dr Yan Beauverd: lead

Study Sites (2)

Geneva University Hospitals

Geneva, 1205, Switzerland

Location

Guy's Hospital

London, SE19RT, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma samples

MeSH Terms

Conditions

Polycythemia Vera; Thrombocythemia, Essential

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders

Study Officials

• Yan Beauverd

  University Hospital, Geneva

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Physician

Study Record Dates

• First Submitted: September 10, 2016
• First Posted: September 23, 2016
• Study Start: September 1, 2016
• Primary Completion: October 31, 2020
• Study Completion: October 31, 2020
• Last Updated: November 10, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); CH (1)