Clinical trial NCT05124041: Goal-Directed Hemostatic Resuscitation Trial in ACLF Induced Coagulopathy
Official title: Thromboelastometry Guided Transfusion Protocol Versus Standard Care in Acute-on-Chronic Liver Failure with Bleeding: a Prospective Intervention Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute on Chronic Liver Failure
Variceal Hemorrhage
Cirrhosis, Liver
Thromboelastometry
Thrombosis;Portal
Lead sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh
Sponsor class: OTHER
First posted: 2021-11-17
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 260 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

Revised Eligibility criteria as per Baveno VII ACLF with variceal bleeding with any indication for blood component transfusion as below

Indications for transfusion in either arm are

1. Multiple sites of bleed e.g. diffuse mucosal ooze, post EVL ulcers, diffuse portal hypertensive gastropathy, etc which are associated with coagulation dysfunction against a background of portal hypertensive bleeding
2. Failure to control bleeding
3. Early rebleeding
4. Active bleeding on endoscopy with refractory variceal bleeding, need for balloon tamponade or self expandable metal stents (SEMS)
5. At the time of bridge therapy to a more definite treatment such as PTFE covered TIPS.
Primary purpose: DIAGNOSTIC

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 260 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

There will be a 'no intervention' group with well controlled bleeding who will undergo VETs but not be offered coagulation correction prophylactically in accordance with the Baveno VII consensus. This control group will be followed up in parallel with the main intervention groups.

The ROTEM or SCT based correction will only be offered to patients who have high risk for rebleeding/ failure to control bleeding/ active bleeding at endoscopy/ need SEMS/TIPS and such individuals will be randomized to 2 arms ROTEM vs SCT, with 130 in each arm.

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.

Eligibility criteria: Patient with ACLF with variceal bleeding is eligible for the study if one or more of the criteria are met following primary endoscopic intervention.

1. Multiple sites of bleed e.g. diffuse mucosal ooze, post EVL ulcers, diffuse portal hypertensive gastropathy, etc which are associated with coagulation dysfunction against a background of portal hypertensive bleeding
2. Failure to control bleeding
3. Early rebleeding
4. Active bleeding on endoscopy with refractory variceal bleeding, need for balloon tamponade or self expandable metal stents (SEMS)
5. At the time of bridge therapy to a more definite treatment such as PTFE covered TIPS.

If one of the above criteria is met, then the patient is enrolled provided they meet the criteria below.

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

Primary outcomes:
measure: Number of participants with clinical control of bleeding
timeFrame: 24 hours
measure: Number of participants with clinical control of bleeding
timeFrame: 5 days
measure: Number of participants with clinical control of bleeding
timeFrame: 42 days
Secondary outcomes:
measure: Duration of Intensive care admission
timeFrame: 30 days after bleeding episode treated by transfusion protocol
measure: Duration of hospital stay
timeFrame: 30 days after bleeding episode treated by transfusion protocol
measure: Number of Participants with Transfusion-related side effects
timeFrame: 30 days after bleeding episode treated by transfusion protocol
measure: Number of Participants with Thromboembolic events
timeFrame: 30 days after bleeding episode treated by transfusion protocol
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education and Research
state: Choose Any State/Province
Study officials:
References: