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

Polycythemia Vera Clinical Trial

— MPNClot  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02912884
• Other study ID #: CCER 2016-00950
• Status: Completed
• Start date: September 2016
• Est. completion date: October 31, 2020

Study information

• Verified date: November 2020
• Source: University Hospital, Geneva
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: October 31, 2020
• Est. primary completion date: October 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Polycythemia
• Polycythemia Vera
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

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

Locations

Country	Name	City	State
Switzerland	Geneva University Hospitals	Geneva
United Kingdom	Guy's Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Dr Yan Beauverd

Countries where clinical trial is conducted

Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Clot permeation; permeation coefficient	Clot permeation will be reported as the calculated permeation coefficient (Ks).	At time of inclusion
Secondary	Quantitative parameters of thrombin generation test (TGT); endogenous thrombin potential (nM*minutes)	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
Secondary	Quantitative parameters of thrombin generation test (TGT); peak (nM)	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
Secondary	Quantitative parameters of thrombin generation test (TGT); time to peak (minutes)	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
Secondary	Fibrin density by laser scanner confocal microscopy (number per 100 µm)	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