Efficacy and Safety of Terlipressin With Albumin Versus Midodrine With Albumin Versus Albumin Alone in Prevention of Paracentesis Induced Circulatory Dysfunction in Cirrhosis

Study Overview
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Brief Summary
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Study Population: Patients admitted or seen in Out Patient Department, Department of Hepatology, Institute of Liver and Biliary Sciences. Study Design: Prospective Open Labeled Randomized Controlled Trial. Study Period: January 2017 to December 2017 Intervention- Subjects will be randomized to 3 groups All patients will receive Standard medical therapy - Albumin-8g/L of tap- one half of dose at beginning of tap and rest half after 6 hours of tapping. Group A - Subjects will receive Terlipressin 1mg intravenous bolus at the onset of paracentesis and the remaining as 1 mg doses intravenous at 8 and 16 h after the first dose. ( total -3mg) Group B - Midodrine 7.5 mg TDS x 3 days Group C - Standard medical therapy only Monitoring and Assessment: Clinical evaluation will be done at regular intervals. Adverse Effects: Rise in blood pressure, arrthymias, hyponatremia and rarely cardiovascular side effects have been noted. Stopping Rule: Development of PICD, hypertension ( BP>160/90mmhg-JNC class II)

Official Title
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Randomized Trial Comparing the Efficacy and Safety of Terlipressin With Albumin Versus Midodrine With Albumin Versus Albumin Alone in Prevention of Paracentesis Induced Circulatory Dysfunction in Cirrhosis

Conditions
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Cirrhosis

Intervention / Treatment
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* Drug: Terlipressin
* Drug: Midodrine
* Drug: Albumin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with cirrhosis who undergo Large volume paracentesis (> 5L) Patients with age from 18-75 years Exclusion Criteria: Renal failure ( Creatinine>1.5mg/dl) Recent Gastrointestinal bleeding within 7 days Spontaneous bacterial Peritonitis Patients with Cardiovascular disease (Electrocardiogram, 2D Echo) Systemic arterial hypertension ( >160/90mmhg) Presence of hepatocellular carcinoma or portal vein thrombosis, Budd chiari syndrome Patients with active untreated sepsis Pregnancy Patients with hepatic encephalopathy No use of drugs affecting systemic hemodynamic 3 days prior to enrollment Refusal to participate

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: Terlipressin<br>Terlipressin 1mg intravenous bolus at the onset of paracentesis and the remaining as 1 mg doses intravenous at 8 and 16 h after the first dose. ( total -3mg) | Drug: Terlipressin<br>* Terlipressin 1mg intravenous bolus at the onset of paracentesis and the remaining as 1 mg doses intravenous at 8 and 16 h after the first dose. ( total -3mg)<br>|
| Active Comparator: Midodrine<br>Midodrine 7.5 mg thrice daily for 3 days. | Drug: Midodrine<br>* Terlipressin 1mg intravenous bolus at the onset of paracentesis and the remaining as 1 mg doses intravenous at 8 and 16 h after the first dose. ( total -3mg)<br>|
| Active Comparator: Standard Medical Therapy<br>Albumin-8g/L of tap- one half of dose at beginning of tap and rest half after 6 hours of tapping. | Drug: Albumin<br>* Albumin-8g/L of tap- one half of dose at beginning of tap and rest half after 6 hours of tapping.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Paracentesis Induced Circulatory Dysfunction (PICD). |  | Day 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of hospital admission withing 28 days in all the 3 groups |  | 28 days | 
| Development of Hyponatremia in all the 3 groups | Hyponatremia is defined as S.Na < 130 meq/dL. | Day 28 | 
| Development of Hepatic Encephalopathy in all the 3 groups | Hepatic Encephalopathy defined as West Haven Grade > 1 | Day 28 | 
| Recurrence of ascites in all the 3 groups |  | Day 28 | 
| Development of Acute Kidney Injury in all the 3 groups | Acute Kidney Injury is defined as increase S.Creatinine by more than 0.3 mg/dL | Day 28 | 
| Survival in all the 3 groups |  | Day 28 |