To Assess Safety and Efficacy of Bolus Versus Continuous Infusion of Terlipressin in Acute Variceal Bleeding

Study Overview
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Brief Summary
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The study is single centered; prospective, parallel arm randomized controlled trial.The patients will be who presented to Institute of Liver & Biliary Sciences with esophageal variceal bleeding or develop esophageal bleeding during hospital stay. All patients will be managed with continuous non-invasive cardiac and hemodynamic monitoring including cardiac rhythm, pulse rate, blood pressure, and oxygen saturation. Hemoglobin (Hb) will checked every 6 h for the initial 48 h and then every 12 h till discharge. Likewise, serum creatinine will checked daily. Packed red blood cells will be transfused to maintain target Hb of ⩾8 g/dl. Patients will be started on IV Proton Pump Inhibitor, with bolus dose of terlipressin (2mg) followed by Endoscopic variceal ligation. All patients will received prophylactic antibiotics; antibiotics will be stopped if there will no other indication to continue. After confirmation of EVB (Esophageal Variceal Bleeding) and successful initial hemostasis with emergency EVBL (Endoscopic Variceal Band ligation), patients will be randomly assigned into Group -A (Bolus terlipressin at 2mg every 4hourly) and Group-B (Continuous infusion of terlipressin @ 4mg/24hour initially) therapy for esophageal varices . They will then undergo HVPG (Hepatic Venous Pressure Gradient) measurement at baseline, 12hours and 24hours. Patient in continuous group will titrate dose. accordingly to HVPG (Hepatic Venous Pressure Gradient) measurement at 12 and 24 hours. At 24 hours patient will be directed to receive either TIPS (Transjugular Intrahepatic Portosystemic Shunt) or will continue Terlipressin for 48 hours.

Official Title
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To Assess Safety and Efficacy of Bolus Versus Continuous Infusion of Terlipressin in Acute Variceal Bleeding: A Randomized Comparison

Conditions
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Acute Variceal Bleeding

Intervention / Treatment
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* Drug: Terlipressin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any patient with only acute esophageal variceal bleeding (as defined by Asian pacific Association for the study of Liver Disease) Informed consent to participate in the study Age 18 to 70 years Exclusion Criteria: Pregnant and lactation Prior treatment with any vasoactive drugs Significant heart or respiratory failure Peripheral arteriopathy clinically significant Previous heart stroke or significant alteration of the Electrocardiogram Hemodynamically unstable Refusal to participate in the study Hypertension

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Bolus Terlipressin<br>Injection terlipressin after 2 mg bolus it will be given 2 mg QID | Drug: Terlipressin<br> <br> |
| Active Comparator: Terlipressin continuous(4mg/24hours)<br>Injection terlipressin after 2 mg bolus it will be given 4 mg over 24 hours,and dose will be titrated as per HVPG (Hepatic Venous Pressure Gradient) | Drug: Terlipressin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of HVPG (hepatic venous pressure gradient) at 24 hours >10% |  | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death in both groups |  | 42 days | 
| Terlipressin related complications in both groups |  | 72 hours | 
| Rebleed within 42 days |  | 42 days | 
| number of blood transfusion requirement at 5 days |  | 5 days | 
| Incidence of ischaemic hepatitis within 5 days |  | 5 days | 
| Incidence of post bleed acute kidney injury within 5 days |  | 5 days | 
| Incidence of post EVL(endoscopic band ligation) ulcer bleed within 5 days |  | 5 days |