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

Sponsor
Dr Yan Beauverd (Other)
Overall Status
Completed
CT.gov ID
NCT02912884
Collaborator
(none)
80
Enrollment
2
Locations
50
Actual Duration (Months)
40
Patients Per Site
0.8
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: No cytoreductive vs cytoreductive drugs

Study Design

Study Type:
Observational
Actual Enrollment :
80 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
Treatment of Polycythaemia Vera and Essential Thrombocythaemia: Influence on the Clot Structure
Actual Study Start Date :
Sep 1, 2016
Actual Primary Completion Date :
Oct 31, 2020
Actual Study Completion Date :
Oct 31, 2020

Arms and Interventions

ArmIntervention/Treatment
PV

Patients with a diagnosis of polycythaemia vera.

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

ET

Patients with a diagnosis of essential thrombocythaemia.

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

Outcome Measures

Primary Outcome Measures

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

  1. Clot permeation; permeation coefficient [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) [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) [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) [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) [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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).

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Geneva University HospitalsGenevaSwitzerland1205
2Guy's HospitalLondonUnited KingdomSE19RT

Sponsors and Collaborators

  • Dr Yan Beauverd

Investigators

  • Principal Investigator: Yan Beauverd, University Hospital, Geneva

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Dr Yan Beauverd, Physician, University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT02912884
Other Study ID Numbers:
  • CCER 2016-00950
First Posted:
Sep 23, 2016
Last Update Posted:
Nov 10, 2020
Last Verified:
Nov 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Nov 10, 2020