Goal-Directed Hemostatic Resuscitation Trial in ACLF Induced Coagulopathy

Study Overview
=================
Brief Summary
-----------------
In this project, we plan to evaluate whether a new, rotational thromboelastometry-guided algorithm (ROTEM) to guide hemostatic resuscitation decreases the use of allogeneic blood products, the total amount of bleeding, transfusion related side effects, thromboembolic complications and costs. Its effect on each patient's post-operative hemostatic profile is also measured. We plan to enroll 140 patients having ACLF with variceal bleeding randomized into two groups: one will be treated conventionally using clinical judgement and standard coagulation tests such as prothrombin time, platelet count, etc. the other treated using a ROTEM-based algorithm. They will be followed for development of rebleeding, complications of transfusion and any signs of infection after hospitalization

Detailed Description
-----------------
Patients with acute-on-chronic liver failure (ACLF) have coagulation failure in the setting of systemic inflammatory syndrome (SIRS), sepsis and extra-hepatic organ failures. The utility of thromboelastography/thromboelastometry currently has unvalidated clinical benefit in the assessment and reversal of coagulopathy among cirrhotic patients as compared to standard coagulation testing.Need for periprocedural blood transfusion is still high in patients with decompensated cirrhosis or ACLF who present with major bleeding. Allogeneic blood transfusion may be detrimental in patients with cirrhosis, due to volume overload and acute lung injury. Viscoelastic testing of global coagulation such as thromboelastometry has been proposed as a superior tool to rapidly diagnose and help guide resuscitation with blood products. In prior studies, we have clarified the pathophysiology of hemostasis in relation to the evidence of sepsis in liver disease and described the accuracy of various available laboratory tests in assessment of these patients. We have described the role of endogenous heparinoids in severe alcoholic hepatitis and the pathogenesis of the coagulation defect in ACLF. We determined the influence of sepsis on coagulation disorders in ACLF patients, to correctly identify the type and optimal quantity of blood product requirement in at risk patients.

Official Title
-----------------
Thromboelastometry Guided Transfusion Protocol Versus Standard Care in Acute-on-Chronic Liver Failure With Bleeding: A Prospective Intervention Trial

Conditions
-----------------
Acute on Chronic Liver Failure, Variceal Hemorrhage, Cirrhosis, Liver, Thromboelastometry, Thrombosis;Portal

Intervention / Treatment
-----------------
* Diagnostic Test: Rotational thromboelastometry


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-65 years ACLF, as diagnosed by CANONIC/ APASL criteria . Upper gastrointestinal bleeding Exclusion Criteria: Current therapy: Recent blood or blood component transfusion in the last 2 weeks. HIV positive/ AIDS patients Patients requiring antiplatelet therapy, Renal insufficiency requiring dialysis Active malignancy within the last 5 years Patient with other neurological disease and metabolic disorders, unbalanced heart failure and/or respiratory failure or end-stage renal disease Administration of anticoagulants, antifibrinolytics, Not willing to participate in the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 140 patients having ACLF with bleeding will be randomized into two groups. One will be treated conventionally, i.e. using clinical judgement and conventional coagulation tests, the other treated using a ROTEM-based algorithm
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ROTEM-arm<br>Treatment of significant blood loss using point-of-care testing of whole blood viscoelasticity (ROTEM) monitoring coagulopathy or hyperfibrinolysis | Diagnostic Test: Rotational thromboelastometry<br>* ROTEM-guided protocol of hemostatic resuscitation<br>|
| Active Comparator: Control-arm<br>Treatment of significant blood loss conventionally, ie. using clinical judgement and conventional coagulation tests, such as prothrombin time (as international normalized ratio, INR), activated partial thrombin time (APTT), fibrinogen in plasma | Diagnostic Test: Rotational thromboelastometry<br>* ROTEM-guided protocol of hemostatic resuscitation<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with clinical control of bleeding | Clinical control of bleeding at 24 hours, at Day 5 and day 42 | 24 hours | 
| Number of participants with clinical control of bleeding | Clinical control of bleeding at 24 hours, at Day 5 and day 42 | 5 days | 
| Number of participants with clinical control of bleeding | Clinical control of bleeding at 24 hours, at Day 5 and day 42 | 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Intensive care admission |  | 30 days after bleeding episode treated by transfusion protocol | 
| Duration of hospital stay |  | 30 days after bleeding episode treated by transfusion protocol | 
| Number of Participants with Transfusion-related side effects |  | 30 days after bleeding episode treated by transfusion protocol | 
| Number of Participants with Thromboembolic events |  | 30 days after bleeding episode treated by transfusion protocol |