Acute on Chronic Liver Failure
Conditions
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.
Interventions
DRUGLactulose
Syp lactulose
DRUGRifaximin
Rifaximin
OTHERStandard Medical treatment
Standard Medical treatment
Sponsors
Institute of Liver and Biliary Sciences, India
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 |
| Incidence of bacterial infection at day 4 and 7 in two arms | day 4 and 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 |
| 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 |
Countries
India
Contacts
Primary ContactDr Shreya Singh, MD
Backup ContactDr Ankur Jindal, DM
Outcome results
None listed