Hepatic Venous Pressure Gradient and Platelet Activation in Chronic Liver Disease

Chronic Liver Disease Clinical Trial

Official title:

Association of Hepatic Venous Pressure Gradient With Platelet Activation in Chronic Liver Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02618798
• Other study ID #: HVPG_Platelets_Version_4.0
• Status: Recruiting
• Phase: N/A
• First received: November 23, 2015
• Last updated: November 30, 2015
• Start date: January 2014
• Est. completion date: January 2016

Study information

• Verified date: November 2015
• Source: Medical University of Vienna
• Contact: Sibylle Pramhas, M.D.
• Phone: +43140400
• Email: sibylle.pramhas[@]meduniwien.ac.at
• Is FDA regulated: No
• Health authority: Austria: Ethics Commitee Medical University Vienna
• Study type: Observational

Clinical Trial Summary

Background: Thrombosis may be crucial in driving the progression of fibrosis in chronic liver disease (CLD). The potential role of platelets and platelet activation in this process is unclear. Platelets participate in inflammation by secretion of pro-inflammatory mediators which may advance hepatic fibrosis. Hepatitis B virus transgenic mice, developed significantly smaller necroinflammatory foci and their serum ALT levels were 80% lower, if they were pre-treated with anti-platelet antibodies. Sinusoidal aggregation of activated platelets also occurs in chronic hepatitis C in humans. It may contribute to thrombocytopenia observed in CLD. Platelet activation is generally believed to be compromised in CLD. However, there is data suggesting that CLD may even be associated with an enhancement of platelet activation. Measurement of hepatic venous pressure gradient (HVPG) constitutes the most common method for estimation of portal venous pressure. HVPG is significantly correlated with histological indices of CLD progression.

Study hypotheses:

1. HVPG as a marker for advancement of hepatic fibrosis and progression of CLD is associated with an increase in platelet activation.

2. Platelet activation and function is not generally compromised in CLD. Comparison of platelet function in CLD to a control group of healthy volunteers is intended to clarify whether CLD leads to a manifest platelet dysfunction

Methods: Study design is observational. 100 patients with CLD of various origins (viral, alcoholic, cholestatic) scheduled for routine HVPG measurement will be enrolled. 30 healthy volunteers will donate blood as a control group. Platelet function and activation will be evaluated by multiple electrode aggregometry (primary outcome variable area under the curve (AUC). Plasma levels of P-selectin (ELISA), PFA (Platelet Function Analyzer) 100™ parameters (EPI-CT and ADP-CT), percentage of P-selectin, GPIIb/IIIa, thrombin receptor positive platelets after stimulation (flow-cytometry) will constitute secondary outcome parameters. Plasmatic coagulation will be evaluated by rotational thrombelastometry (ROTEM). Platelet count and routine coagulation parameters will be monitored. HVPG measurement by hepatic vein catheterization and patient blood sampling will be carried out via the internal jugular vein. Blood sampling in volunteers will be performed via the antecubital vein

Study Rationale: If higher levels of platelet activation are associated with increased HVPGs, this would provide an insight into the pathogenesis of CLD. It would also point toward a possible benefit of anti-platelet therapy in CLD. Verification of platelet dysfunction in CLD is relevant to clinical practice in anaesthesiology and intensive care as procedures are often postponed in CLD-patients for fear of bleeding complications. CLD patients may also receive prophylactic platelet concentrates prior to interventions which is costly, fraught with risk of bacterial infection and may be unnecessary in the absence of platelet dysfunction.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years to 90 Years

Eligibility

Inclusion Criteria:

• Confirmed chronic liver disease (CLD), alcoholic, viral, cholestatic.

• CHILD-PUGH Stage A, B, C, and non-cirrhotics

• Planned routine measurement of HVPG.

• Age: 19 years or older

Exclusion Criteria:

• Impaired kidney function (Creatinine > 1.3mg/dl)

• Platelet count < 50,000/µl

• Participation in a clinical trial in the 3 weeks preceding the study

• IFN-therapy within 6 months of inclusion into the study.

• Use of anti-thrombotic or anticoagualant medication

• Pregnancy

• Intra or extra-hepatic malignancy

• Haemostatic diseases other than cirrhosis

• Current abuse of alcohol (Abstinence from alcohol for at least 6 weeks preceding the study is required)

Study Design

Observational Model: Case-Only, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Chronic Liver Disease
• Liver Diseases

Locations

Country	Name	City	State
Austria	Department of Special Anesthesia and Pain Therapy, Medical University of Vienna, AKH Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Multiple electrode aggregometry (MEA) parameter area under the curve (AUC)		Single measurement within study duration of two years	No
Secondary	MEA parameters velocity (AU/min)		Single measurement within study duration of two years	No
Secondary	Aggregation (AU)		Single measurement within study duration of two years	No
Secondary	Percentage (%) of P-selectin positive platelets	FACS	Single measurement within study duration of two years	No
Secondary	Percentage (%) GPIIa/IIIb receptor positive platelets	FACS	Single measurement within study duration of two years	No
Secondary	Percentage (%) thrombin receptor positive platelets	FACS	Single measurement within study duration of two years	No
Secondary	P-selectin plasma level		Single measurement within study duration of two years	No
Secondary	Serotonin plasma level		Single measurement within study duration of two years	No
Secondary	Rotational thrombelastometry parameter: CT (coagulation time) (seconds)		Single measurement within study duration of two years	No
Secondary	Rotational thrombelastometry parameter: CFT (clot formation time) (seconds)		Single measurement within study duration of two years	No
Secondary	Rotational thrombelastometry parameter: MCF (maximum clot firmness) (mm)		Single measurement within study duration of two years	No