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

Not Applicable

Not yet recruiting

• Conditions: Acute on Chronic Liver Failure
• Interventions: Drug: Lactulose; Other: Standard Medical treatment; Drug: Rifaximin

• Registration Number: NCT06808009
• Lead Sponsor: Institute of Liver and Biliary Sciences, India

Brief Summary

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.

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 Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-01-29
• Study First Submitted QC: 2025-02-03
• Last Update Submitted: 2025-02-03
• Study First Posted: 2025-02-04
• Last Update Posted: 2025-02-04
• Study Start: 2025-02-05
• Primary Completion: 2026-02-28
• Study Completion: 2026-02-28

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 90

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
lactulose and rifaximin	Lactulose	T. Rifaximin 550 mg po bd Syp Lactulose to ensure 2-3 motions
lactulose and rifaximin	Rifaximin	T. Rifaximin 550 mg po bd Syp Lactulose to ensure 2-3 motions
Standard Medical Treatment	Standard Medical treatment	Routine medicines, Albumin Iv antibiotics,Protein powder , branched chain amino acids

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

Institute of Liver & Biliary Sciences (ILBS); 🇮🇳 New Delhi, Delhi, India