Clinical trial NCT06808009: Goal Directed Ammonia Lowering Therapy in Hyperammonemic ACLF Patients With no Overt HE to Reduce Major Adverse Liver Related Outcomes (GOAL Trial)
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Acute on Chronic Liver Failure
Lead sponsor: Institute of Liver and Biliary Sciences, India
Sponsor class: OTHER
First posted: 2025-02-04
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: Day 7
Secondary outcomes:
measure: Incidence of bacterial infection at day 4 and 7 in two arms
timeFrame: day 4 and 7
measure: Incidence of overt HE at day 4 and 7 in two arms
timeFrame: day 4 and 7
measure: Proportion of patients with AARC III ACLF at day 4 and 7 in two arms
timeFrame: day 4 and 7
measure: Incidence of new AKI, SBP, Variceal bleed at day 4 and 7 in two arms
timeFrame: day 4 and 7
measure: Proportion of patients with ammonia <79.5 mmol/L(135mcg/dl) at day 1,2,3 and day 7 in 2 arms
timeFrame: day 1,2,3 and day 7
measure: Proportion of patients with >25% and 50% ammonia reduction at day 1,2,3 and day 7 in 2 arms
timeFrame: day 1,2,3 and day 7
measure: Liver related mortality at day 28 and day 90
timeFrame: day 28 and day 90
measure: Changes in markers of systemic inflammation from baseline and day 7 in two arms
timeFrame: day 7
measure: Adverse effect of ammonia lowering therapies
timeFrame: day 90
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Institute of Liver & Biliary Sciences (ILBS)
state: Delhi
Study officials:
References: