Comparison of Three Transfusion Strategies for Central Venous Catheterization in Cirrhotics: A Randomized Clinical Trial

Study Overview
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Brief Summary
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The aim of this study is to compare three different blood transfusion strategies for coagulopathy correction before central venous catheterization in patients with chronic liver failure (cirrhosis and/or chronic liver graft dysfunction) admitted in intensive care unit.

Detailed Description
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Central venous catheterization is a ubiquitous procedure in intensive care units and is mainly used for drug administration, hemodynamic monitoring and hemodialysis. Only in US more than five million catheters are inserted annually. One of the main complications associated to central venous lines are the mechanical ones, i.e. arterial puncture, bleeding and hematoma formation, which varies between 5% and 19%. The use of real-time ultrasonography to accomplish central venous catheterization was associated to a drastic reduction in complication rates, and when performed by trained personnel, some series show complications rates <1%, even in patients with coagulopathy. Patients presenting with chronic liver failure has a complex coagulation system balance, resulting from reduction in the majority of procoagulant and anticoagulant factors, opposed by preservation of thrombin generation. Thus, these patients are prone to develop hemorrhagic and thrombotic phenomena. The coagulation of cirrhotic patients have been classically evaluated by standard coagulation tests. Nevertheless, these tests present important limitations, as evaluation of plasmatic component only, and do not predict bleeding risk. The thromboelastometry is a point-of-care real-time coagulation system evaluation with the advantage of evaluating the cellular and plasmatic components of the coagulation and present a more comprehensive evaluation of blood coagulation, specially in cirrhotics. This technology is associated with reduced costs in diverse clinical settings. In clinical practice, approximately 90% of physicians empirically transfuse blood components to cirrhotic patients before invasive procedures. This practice is associated to increased risks related to blood transfusion per se, e.g. blood borne infections, immunologic and non-immunologic adverse reactions, to cite some. Several randomized clinical trials have shown that restrictive blood transfusion strategies are associated to better outcomes, including mortality.

Official Title
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Point-of-care Versus Standard Coagulation Tests Versus Restrictive Strategy to Guide Transfusion in Chronic Liver Failure Patients Requiring Central Venous Line: Prospective Randomized Trial

Conditions
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Liver Cirrhosis

Intervention / Treatment
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* Other: Coagulogram-based protocol
* Other: Thromboelastometry-based protocol
* Other: Restrictive strategy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic liver failure (cirrhosis or chronic graft dysfunction) from any cause and medical indication of central venous line placement Exclusion Criteria: Acute liver failure or Use of therapeutic doses of oral or parenteral anticoagulants (unfractionated heparin or low molecular weight heparin or oral anticoagulants) or Use of oral or parenteral platelet aggregation inhibitors or Patients with von Willebrand syndrome or Over-the-guidewire central venous catheter changing Patients previously included in this study protocol during the same hospital stay

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Coagulogram-based protocol<br>Arm based on standard coagulation tests protocol to guide blood transfusion before central venous catheterization. The possible components to be used include fresh frozen plasma, platelets (random or aphaeresis) and or cryoprecipitate. | Other: Coagulogram-based protocol<br>* The interventions for this protocol include transfusion of fresh frozen plasma, platelets (random or aphaeresis) and/or cryoprecipitate, based on international normalised ratio (INR), partial thromboplastin time (PTT), platelet count and/or fibrinogen. If INR >1.5 or PTT >50 sec., fresh frozen plasma is administered (dose: 10 mL/Kg); and/or platelets <50,000/microliter, random or aphaeresis platelets are administered (01 unit/Kg or 01 aphaeresis); and/or fibrinogen <150 mg/dL, cryoprecipitate is administered (dose: 01 unit/Kg).<br>|
| Experimental: Thromboelastometry-based protocol<br>Arm based on rotational thromboelastometry (ROTEM(R)) protocol to guide blood transfusion before central venous catheterization. The possible components to be used include fresh frozen plasma, platelets (random or aphaeresis) and or cryoprecipitate. | Other: Thromboelastometry-based protocol<br>* The interventions for this protocol include transfusion of fresh frozen plasma, platelets (random or aphaeresis) and/or cryoprecipitate, based on rotational thromboelastometry (ROTEM(R)). If CTex <80 sec. and A10ex >40 mm, then no blood transfusion is performed; when CTex >80s, then fresh frozen plasma is administered (dose: 10 mL/Kg); and/or A10ex <40 mm or A10fib >10 mm, random or aphaeresis platelets are administered (01 unit/Kg or 01 aphaeresis); and/or A10ex <40 mm or A10fib <10 mm, cryoprecipitate is administered (dose: 01 unit/Kg).<br>|
| Experimental: Restrictive strategy<br>Arm based on a restrictive protocol strategy based on INR/PT and platelets count. The possible components to be used include fresh frozen plasma and/or platelets (random or aphaeresis). | Other: Restrictive strategy<br>* The interventions for this protocol include transfusion of fresh frozen plasma and/or platelets (random or aphaeresis), based on INR and platelet count. If INR >5, fresh frozen plasma is administered (dose: 10 mL/Kg); and/or platelets <25,000/microliter, random or aphaeresis platelets are administered (01 unit/Kg or 01 aphaeresis).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients submitted to blood components transfusion - i.e. fresh frozen plasma, platelets and/or cryoprecipitate - before central venous catheterization |  | Day of randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of hemorrhagic complications associated to central venous catheterization procedure |  | Day 1 | 
| Incidence of acute immunologic and non-immunologic adverse effects of blood transfusion |  | Day 1 | 
| Costs assessments (laboratory and blood transfusion) between the three strategies |  | Day 1 | 
| Length of stay in ICU |  | Up to 90 days | 
| Length of stay in hospital |  | Up to 180 days | 
| Mortality rate |  | Up to 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver cirrhosis, Blood coagulation, Thromboelastography, Blood transfusion, Catheterization, central venous