Goal Directed Ammonia Lowering Therapy in Hyperammonemic ACLF Patients With no Overt HE to Reduce Major Adverse Liver Related Outcomes (GOAL Trial)

Goal Directed Ammonia Lowering Therapy in Hyperammonemic ACLF Patients With no Overt HE to Reduce Major Adverse Liver Related Outcomes (GOAL Trial)- A Randomized Controlled Trial

SIRS in ACLF exacerbate adverse effects of ammonia - sarcopenia, infections, immune dysfunction, HE and organ dysfunction Persistent or incident hyperammonemia during first week of hospitalization in patients with ACLF is associated with increased risk of organ failure and death. Prospective studies on the efficacy of ammonia lowering therapies on major adverse liver related outcomes (MALO) (any of AARC III, bacterial infection, overt HE grade or death) in hyperammonemic ACLF patients with no overt HE are limited. In this study we aim to to compare the safety and efficacy of ammonia lowering therapy (goal directed lactulose and rifaximin) compared to SMT to prevent major liver related outcomes (MALO) (any of AARC III, bacterial infection, overt HE grade or death) in hyperammonemic ACLF patients with no overt HE.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute on Chronic Liver Failure
• Intervention / Treatment: Drug: Rifaximin; Drug: Lactulose; Other: Standard Medical treatment

Detailed Description

Hypothesis: Goal directed ammonia lowering therapy in hyperammonemic ACLF patients with no overt HE leads to reduced incidence of major adverse liver related outcomes (MALO) (any of AARC III, bacterial infection, overt HE grade or death) at day 7, 28 and day 90.

AIM:- To compare the safety and efficacy of ammonia lowering therapy (goal directed lactulose and rifaximin) compared to SMT to prevent major liver related outcomes (MALO) (any of AARC III, bacterial infection, overt HE grade or death) in hyperammonemic ACLF patients with no overt HE.

Study design:

• A Prospective Randomized Controlled Trial.
• Single Centre.
• Open label.
• Block Randomization will be done , it will be implemented by IWRS method.
• The study will be conducted in Department of Hepatology, ILBS.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dr Ankur Jindal, DM; Phone Number: 01146300000; Email: ankur.jindal3@gmail.com
• Study Contact Backup: Name: Dr Shreya Singh, MD; Phone Number: 01146300000; Email: shreyasingh2746@gmail.com

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of Liver & Biliary Sciences (ILBS)
      • Contact: Dr Shreya Singh, MD; Phone Number: 01146300000; Email: shreyasingh2746@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-70 years
2. ACLF as per APASL criteria (AARC grade I/II)
3. Baseline ammonia levels of ≥135ug/dl or 79.5umol/l
4. Given informed consent

Exclusion Criteria:

• 1. Overt HE 2. AARC grade III 3. Confirmed or suspected bacterial infection 4. Extrahepatic organ failure 5. Renal dysfunction lasting for more than 48 hours or need for vasoconstrictors 6. Paralytic ileus 7. Patients with hepatocellular carcinoma beyond Milan criteria or any other neoplastic disorder 8. Pregnant and lactating women 9. Use of lactulose, rifaximin or LOLA in past 48h 10. Uncontrolled DM, HT, CAD 11. Patients with allergy or other contraindications of the used drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lactulose and rifaximin; T. Rifaximin 550 mg po bd Syp Lactulose to ensure 2-3 motions	Drug: Rifaximin; Rifaximin; Drug: Lactulose; Syp lactulose
Active Comparator: Standard Medical Treatment; Routine medicines, Albumin Iv antibiotics,Protein powder , branched chain amino acids	Other: Standard Medical treatment; Standard Medical treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients achieving composite endpoint target NH3 level < 79.5 mmol/L (135mcg/dl) and /or Incidence of major adverse liver related outcomes (MALO) (any of AARC III, bacterial infection, overt HE grade or death) at day 7 in two arms.	Day 7

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of bacterial infection at day 4 and 7 in two arms	day 4 and 7
Incidence of overt HE at day 4 and 7 in two arms	day 4 and 7
Proportion of patients with AARC III ACLF at day 4 and 7 in two arms	day 4 and 7
Incidence of new AKI, SBP, Variceal bleed at day 4 and 7 in two arms	day 4 and 7
Proportion of patients with ammonia <79.5 mmol/L(135mcg/dl) at day 1,2,3 and day 7 in 2 arms	day 1,2,3 and day 7
Proportion of patients with >25% and 50% ammonia reduction at day 1,2,3 and day 7 in 2 arms	day 1,2,3 and day 7
Liver related mortality at day 28 and day 90	day 28 and day 90
Changes in markers of systemic inflammation from baseline and day 7 in two arms	day 7
Adverse effect of ammonia lowering therapies	day 90

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Estimated): February 5, 2025
• Primary Completion (Estimated): February 28, 2026
• Study Completion (Estimated): February 28, 2026

Study Registration Dates

• First Submitted: January 29, 2025
• First Submitted That Met QC Criteria: February 3, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 3, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Hepatic Insufficiency; Liver Failure, Acute; End Stage Liver Disease; Liver Failure; Acute-On-Chronic Liver Failure; Anti-Bacterial Agents; Anti-Infective Agents; Gastrointestinal Agents; Rifaximin; Lactulose
• Other Study ID Numbers: ILBS-ACLF-23

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