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

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

• 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)

Study Overview

• Status: Completed
• Conditions: Cirrhosis
• Intervention / Treatment: Drug: Terlipressin; Drug: Midodrine; Drug: Albumin

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of liver and Biliary Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with cirrhosis who undergo Large volume paracentesis (> 5L)
2. Patients with age from 18-75 years

Exclusion Criteria:

1. Renal failure ( Creatinine>1.5mg/dl)
2. Recent Gastrointestinal bleeding within 7 days
3. Spontaneous bacterial Peritonitis
4. Patients with Cardiovascular disease (Electrocardiogram, 2D Echo)
5. Systemic arterial hypertension ( >160/90mmhg) Presence of hepatocellular carcinoma or portal vein thrombosis, Budd chiari syndrome
6. Patients with active untreated sepsis
7. Pregnancy
8. Patients with hepatic encephalopathy
9. No use of drugs affecting systemic hemodynamic 3 days prior to enrollment
10. Refusal to participate

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Terlipressin; 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; 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)
Active Comparator: Midodrine; Midodrine 7.5 mg thrice daily for 3 days.	Drug: Midodrine; 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)
Active Comparator: Standard Medical Therapy; Albumin-8g/L of tap- one half of dose at beginning of tap and rest half after 6 hours of tapping.	Drug: Albumin; Albumin-8g/L of tap- one half of dose at beginning of tap and rest half after 6 hours of tapping.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2017
• Primary Completion (Actual): April 30, 2018
• Study Completion (Actual): April 30, 2018

Study Registration Dates

• First Submitted: May 5, 2017
• First Submitted That Met QC Criteria: May 8, 2017
• First Posted (Actual): May 9, 2017

Study Record Updates

• Last Update Posted (Actual): September 5, 2018
• Last Update Submitted That Met QC Criteria: September 1, 2018
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Adrenergic alpha-1 Receptor Agonists; Terlipressin; Midodrine
• Other Study ID Numbers: ILBS-Cirrhosis-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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