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

November 9, 2020 updated by: Dr Yan Beauverd

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

80

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Geneva, Switzerland, 1205
        • Geneva University Hospitals
  • United Kingdom
      • London, United Kingdom, SE19RT
        • Guy's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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).

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
At time of inclusion
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.
At time of inclusion
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)
At time of inclusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clot permeation; permeation coefficient
Time Frame: At time of inclusion
Clot permeation will be reported as the calculated permeation coefficient (Ks).
At time of inclusion
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.
At time of inclusion
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.
At time of inclusion
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.
At time of inclusion
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.
At time of inclusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dr Yan Beauverd

Investigators

  • Principal Investigator: Yan Beauverd, University Hospital, Geneva

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 1, 2016

Primary Completion (ACTUAL)

October 31, 2020

Study Completion (ACTUAL)

October 31, 2020

Study Registration Dates

First Submitted

September 10, 2016

First Submitted That Met QC Criteria

September 20, 2016

First Posted (ESTIMATE)

September 23, 2016

Study Record Updates

Last Update Posted (ACTUAL)

November 10, 2020

Last Update Submitted That Met QC Criteria

November 9, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCER 2016-00950

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Polycythemia Vera

Clinical Trials on No cytoreductive vs cytoreductive drugs

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Gambia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe