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

NCT06808009 | Not Yet Recruiting

• 1 other identifier: ILBS-ACLF-23
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute on Chronic Liver Failure

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• 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

Study Arms (2)

lactulose and rifaximin

EXPERIMENTAL

T. Rifaximin 550 mg po bd Syp Lactulose to ensure 2-3 motions

Drug: Lactulose; Drug: Rifaximin

Standard Medical Treatment

ACTIVE COMPARATOR

Routine medicines, Albumin Iv antibiotics,Protein powder , branched chain amino acids

Other: Standard Medical treatment

Interventions

Lactulose DRUG

Syp lactulose

lactulose and rifaximin

Rifaximin DRUG

Rifaximin

lactulose and rifaximin

Standard Medical treatment OTHER

Standard Medical treatment

Standard Medical Treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• \. 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

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (1)

Institute of Liver & Biliary Sciences (ILBS)

New Delhi, National Capital Territory of Delhi, 110070, India

Location

MeSH Terms

Conditions

Acute-On-Chronic Liver Failure

Interventions

Lactulose; Rifaximin

Condition Hierarchy (Ancestors)

Liver Failure, Acute; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Central Study Contacts

Dr Shreya Singh, MD

CONTACT

01146300000; shreyasingh2746@gmail.com

Dr Ankur Jindal, DM

CONTACT

01146300000; ankur.jindal3@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2025
• First Posted: February 4, 2025
• Study Start: February 5, 2025
• Primary Completion: February 28, 2026
• Study Completion: February 28, 2026
• Last Updated: February 4, 2025

Record last verified: 2025-01

Locations

IN (1)