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Completed

NCT Number: NCT02912884

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

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Geneva University Hospitals, Geneva, Switzerland

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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).

Treatment and study plan

No cytoreductive vs cytoreductive drugs

Drug

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

Primary outcomes

  1. Fibrin polymerization; lag-time (in seconds)

    Time frame: At time of inclusion

    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).

  2. Fibrin polymerization; maximal absorbance

    Time frame: At time of inclusion

    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.

  3. Clot lysis time (in minutes)

    Time frame: At time of inclusion

    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)

Secondary outcomes

  1. Clot permeation; permeation coefficient

    Time frame: At time of inclusion

    Clot permeation will be reported as the calculated permeation coefficient (Ks).

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

    Time frame: At time of inclusion

    The measurement of thrombin generation is performed by the technique of calibrated automated thrombogram (CAT). Endogenous thrombin potential will be reported in nM*minutes.

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

    Time frame: At time of inclusion

    The measurement of thrombin generation is performed by the technique of calibrated automated thrombogram (CAT). Peak will be reported in nM.

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

    Time frame: At time of inclusion

    The measurement of thrombin generation is performed by the technique calibrated automated thrombogram (CAT). Time to peak will be reported in minutes.

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

    Time frame: At time of inclusion

    The fibrin density was determined by counting the number of fibres crossing an arbitrary line of 100 μm drawn through a single optical section. Each fibrin clot is prepared in duplicate and 20 density measurements were performed on each sample.

Sponsors and collaborators

Lead sponsor

Dr Yan Beauverd

Other

Registry information

Acronym: MPNClot

Important dates

Study start
2016
Primary completion
2020
Study completion
2020
First posted
Sep 23, 2016
Registry last updated
Nov 10, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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