To Compare the Response Rate of Noradrenaline vs. Terlipressin in Hepatorenal Syndrome in Patients With Acute on Chronic Liver Failure

Study Overview
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Brief Summary
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Continous infusion of nor adrenaline + albumin Continous infusion of terlipressin + albumin Response will assessed at every 48 hour (i) Complete response: Regression of acute kidney injury stage with reduction of S. Cr within 0.3 mg/dl of baseline (ii) Partial response: Regression of acute kidney injury stage with reduction of S. Cr to ≥0.3 mg/dl above baseline (iii) No response: No regression of acute kidney injury Treatment will be extended until reversal of HRS (decrease in creatinine below 1.5 mg/dL) or for a maximum of 7 days after rescue treatment will be followed. If intolerant to terlipressin, excluded from study and rescue treatment will be given in form of noradrenaline or octreotide and midodrine.

Official Title
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''To Compare the Response Rate of Noradrenaline vs. Terlipressin in Hepatorenal Syndrome in Patients With Acute on Chronic Liver Failure'

Conditions
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Acute on Chronic Liver Failure

Intervention / Treatment
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* Drug: Nor adrenaline + albumin
* Drug: Terlipressin + albumin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with acute on chronic liver failure presenting with hepatorenal syndrome Patients consented for the study protocol by signing the informed consent. Exclusion Criteria: Age less than 18 years Decompensated cirrhotics Evidence of chronic kidney disease Patients undergoing renal replacement therapy (hemo-dialysis/renal transplantation). Post liver transplantation patients. History of coronary artery disease, ischaemic cardiomyopathy, ventricular arrhythmia, or peripheral vascular disease. Patients with obstructive uropathy. Patient who withdrew or non complaint to the study protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nor Adrenaline + Albumin<br>Intravenous continous infusion of terlipressin at the dose of 2 mg every 24 hours with the maximum daily cumulative dose of 12 mg/day. In case of no response the dose of the terlipressin will be progressively increased to the maximum infusion dose of 12 mg/24 hour. Patients will be given 1g/Kg of albumin per day, which will be discontinued if CVP is more than 18 cm H2O. | Drug: Nor adrenaline + albumin<br> <br> |
| Active Comparator: Terlipressin + Albumin<br>Continuous IV infusion of NA starting at 0.5 mg/h with doubling of dose after every 4 hours designed to achieve an increase in MAP of at least 10 mmHg or an increase in 4-h urine output of more than 200 ml. When one of these goals was not achieved, the noradrenaline dose was increased every 4 h in steps of 0.5 mg/h, up to the maximum dose of 3 mg/h. Patients will be given 1g/Kg of albumin per day, which will be discontinued if CVP is more than 18 cm H2O. | Drug: Terlipressin + albumin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to treatment in each intervention group | Complete response: Regression of acute kidney injury stage with reduction of S. Cr within 0.3 mg/dl of baseline (ii) Partial response: Regression of acute kidney injury stage with reduction of S. Cr to ≥0.3 mg/dl above baseline (iii) No response: No regression of acute kidney injury. | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | 28 days | 
| Drug related Side effects/complications |  | 28 days |