Efficacy and Safety of Continuous Infusion of Terlipressin vs Bolus Terlipressin in ACLF Patients With Acute Esophageal Variceal Bleed

Efficacy and Safety of Continuous Infusion of Terlipressin vs Bolus Terlipressin in ACLF Patients With Acute Esophageal Variceal Bleed: Pilot Study

Acute portal hypertension, as measured by rapid rise in hepatic venous pressure gradient (HVPG) can lead to further dreaded complications, including acute variceal bleeding (AVB) AVB: 6-week mortality rates of around 15-20% in patients with chronic liver disease without ACLF.The overall prevalence of UGH in cirrhotic patients with AD was 34.4% and 35.7% in patients with ACLF.AVB is a well-recognized precipitant leading to the occurrence and development of ACLF. AVB is a well-recognized precipitant leading to the occurrence and development of ACLF. Medical therapy for esophageal variceal bleeding (EVB) aims to reduce the splanchnic blood flow and portal pressure. The most common vasoactive agents include terlipressin, vasopressin, somatostatin, and octreotide.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute on Chronic Liver Failure
• Intervention / Treatment: Drug: Terlipressin Injectable Product

Detailed Description

Aim and Objective - To assess the safety and efficacy of continuous terlipressin vs. Bolus terlipressin in the management of acute esophageal variceal bleeding in ACLF.

Study population: Adult patients (age ≥ 18 years) diagnosed with ACLF presenting with upper GI bleeding due to esophageal varices Study design: Pilot study Study period: 1 year Sample size: 60

Intervention:

Group I- Intravenous terlipressin (administered as a continuous infusion at 4 mg/24 hours). After 12 hours, if the hepatic venous pressure gradient (HVPG) does not show a reduction of less than 10%, increase the dose to 6 mg/24 hours.

Group II- Intravenous terlipressin (2 mg initially every 4 hourly for 2 days and then 1 mg every 4 hrs)

Monitoring and assessment: All patients would undergo vital and baseline parameter screening before randomization. Based on randomization they will receive either steroid or plasma exchange followed by steroid

Adverse effects:

Acute Diarrhea, chest pain, Arterial hypertension, Cardiac arrhythmias, Acute abdomen Stopping rule: chest pain, alteration of ECG, cyanosis, bradycardia, severe allergic rashes

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Dr Khushboo Yadav, MD; Phone Number: 01146300000; Email: ky29277@gmail.com
• Study Contact Backup: Name: Dr Vinod S Arora, DM; Phone Number: 01146300000; Email: VINOD_UCMS@yahoo.com

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of Liver & Biliary Sciences (ILBS)
      • Contact: Dr Khushboo Yadav, MD; Phone Number: 01146300000; Email: ky29277@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult patients (age ≥ 18 years) diagnosed with ACLF presenting with due to esophageal varices bleeding.

Exclusion Criteria:

1. Age < 18 years
2. History of coronary heart disease or ventricular arrhythmia,
3. Stroke or transient ischemic attack,
4. Bronchial asthma,
5. Epilepsy,
6. Pregnancy,
7. Rebleeding.
8. HCC
9. Gastric variceal bleed

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bolus terlipressin; 2 mg initially every 4 hourly for 2 days and then 1 mg every 4 hrs.	Drug: Terlipressin Injectable Product; Terlipressin Injectable Product
Experimental: Continous Infusion of Terlipressin; Administered as a continuous infusion at 4 mg/24 hours. After 12 hours, if the hepatic venous pressure gradient (HVPG) does not show a reduction of less than 10%, increase the dose to 6 mg/24 hours.	Drug: Terlipressin Injectable Product; Terlipressin Injectable Product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Hepatic venous Pressure Gradient (HVPG) reduction of more than 10% from baseline at 12-24 hours in both arms.	12-24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Failure to control hemostasis	5 days
Terlipressin-related complications within 5 days i.e. safety of the drug	5 days
Number of blood transfusions at 5 days	5 days
Rebleed within 42 day	42 days
Incidence of post-bleed Acute Kidney Injury within 5 days	5 days
6 weeks mortality in both groups.	6 weeks

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Estimated): February 10, 2025
• Primary Completion (Estimated): February 28, 2026
• Study Completion (Estimated): February 28, 2026

Study Registration Dates

• First Submitted: January 30, 2025
• First Submitted That Met QC Criteria: February 6, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 6, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Hepatic Insufficiency; Liver Failure, Acute; End Stage Liver Disease; Liver Failure; Acute-On-Chronic Liver Failure; Antihypertensive Agents; Vasoconstrictor Agents; Terlipressin
• Other Study ID Numbers: ILBS-ACLF-22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No