Goal-Directed Hemostatic Resuscitation Trial in ACLF Induced Coagulopathy (GOODHEART-ACLF)

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

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.

Study Overview

• Status: Completed
• Conditions: Cirrhosis, Liver; Acute on Chronic Liver Failure; Variceal Hemorrhage; Thromboelastometry; Thrombosis;Portal
• Intervention / Treatment: Diagnostic test: Rotational thromboelastometry

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.

• Study Type: Interventional
• Enrollment (Actual): 262
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Choose Any State/Province
    • Chandigarh, Choose Any State/Province, India, 160012
      • Postgraduate Institute of Medical Education and Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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. Active bleeding on endoscopy with refractory variceal bleeding, need for balloon tamponade or self expandable metal stents (SEMS)
4. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ROTEM-arm; Treatment of significant blood loss using point-of-care testing of whole blood viscoelasticity (ROTEM) monitoring coagulopathy or hyperfibrinolysis	Diagnostic test: Rotational thromboelastometry; ROTEM-guided protocol of hemostatic resuscitation
Active Comparator: Control-arm; 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; ROTEM-guided protocol of hemostatic resuscitation

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	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

Collaborators and Investigators

• Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2021
• Primary Completion (Actual): January 15, 2026
• Study Completion (Actual): January 15, 2026

Study Registration Dates

• First Submitted: November 5, 2021
• First Submitted That Met QC Criteria: November 5, 2021
• First Posted (Actual): November 17, 2021

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency; Fibrosis; Liver Failure, Acute; Pathological Conditions, Signs and Symptoms; Liver Cirrhosis; Acute-On-Chronic Liver Failure
• Other Study ID Numbers: PGI/IEC/2020/000268; PGI/IEC/2024/EIC000462 27.3.24 (Other Identifier: PGIMER Institutional review board)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No