Midodrine Versus Albumin for Prevention of Paracentesis Induced Circulatory Disturbance

Midodrine Versus Albumin During Large-volume Paracentesis and Its Effect on Paracentesis Induced Circulatory Disturbance in Patients With Acute on Chronic Liver Failure - A Randomized Controlled Trial

Paracentesis-induced circulatory disturbance (PICD) is a very common cause of mortality and morbidity in patients undergoing large-volume paracentesis. Albumin is commonly used in decompensated cirrhosis during large-volume paracentesis. However, it may not be cost-effective and has side effects like volume overload and transfusion reactions.

Therefore the investigator proposed to use midodrine which is a drug that increases the mean arterial pressure. The investigators hypothesized that midodrine may be effective in preventing PICD in acute on chronic liver failure patients requiring modest paracentesis. This has already been found to be effective in initial studies in decompensated cirrhosis

Study Overview

• Status: Completed
• Conditions: Paracentesis-Induced Circulatory Dysfunction
• Intervention / Treatment: Drug: Human Albumin 20%; Drug: Midodrine Hydrochloride

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Telangana
    • Hyderabad, Telangana, India, 500032
      • Asian Institute of Gastroenterology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Consecutive patients above 18 years of age who fulfilled Asia Pacific Association of study of liver disease (APASL) criteria for ACLF and required paracentesis for moderate to tense ascites were included in the study.
2. Acute on Chronic Liver Failure (ACLF) was defined as an acute hepatic insult manifesting as jaundice (Serum bilirubin ≥ 5 mg/dL (85 micromole/L) and coagulopathy (INR ≥ 1.5 or prothrombin activity < 40%) complicated within 4 weeks by clinical ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease/cirrhosis and is associated with a high 28-day mortality -

Exclusion Criteria:

1. Patients with acute kidney injury defined as serum creatine of > 0.3 mg/dl above the baseline
2. Severe cardiopulmonary disease
3. History of urinary retention
4. Pheochromocytoma
5. Thyrotoxicosis
6. Persistent and excessive supine hypertension define by systolic blood pressure > 150 mm Hg
7. Pregnant patients
8. Unable to give informed consent were excluded from the study -

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm receiving 20% Human Albumin; 20% Human albumin given intravenously over 4 hours	Drug: Human Albumin 20%; Human ALbumin 20% for prevention of paracentesis induced circulatory disturbance
Experimental: Arm receiving Midodrine; Tablet Midodrine 2.5 mg - 3 tablets thrice daily orally starting just before paracentesis	Drug: Midodrine Hydrochloride; Midodrine hydrochloride for PICD prevention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevention of Paracentesis induced circulatory disturbance	Measure the value of plasma renin activity on sixth day after paracentesis	Day 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost effectiveness of Midodrine versus Albumin	Cost effectiveness of use of Midodrine compared to Albumin	Day 6
Hepatic Encephalopathy as measured by West-Haven criteria	Hepatic encephalopathy as measured by the West Haven criteria on day 6 in both midodrine and albumin groups	Day 6
Renal outcome post paracentesis	Serum creatinine, serum sodium and serum potassium values on day 6 after paracentesis	Day 6

Collaborators and Investigators

• Sponsor: Asian Institute of Gastroenterology, India
• Investigators: Principal Investigator: MITHUN SHARMA, MD FACG AGAF, Asian Institute of Gastroenterology

Publications and helpful links

General Publications

• Shrestha DB, Budhathoki P, Sedhai YR, Baniya R, Awal S, Yadav J, Awal L, Davis B, Kashiouris MG, Cable CA. Safety and efficacy of human serum albumin treatment in patients with cirrhotic ascites undergoing paracentesis: A systematic review and meta-analysis. Ann Hepatol. 2021 Dec;26:100547. doi: 10.1016/j.aohep.2021.100547. Epub 2021 Oct 6.
• Kulkarni AV, Kumar P, Sharma M, Sowmya TR, Talukdar R, Rao PN, Reddy DN. Pathophysiology and Prevention of Paracentesis-induced Circulatory Dysfunction: A Concise Review. J Clin Transl Hepatol. 2020 Mar 28;8(1):42-48. doi: 10.14218/JCTH.2019.00048. Epub 2020 Mar 26.
• Bai M, Han G. Midodrine for paracentesis-induced circulatory dysfunction. J Clin Gastroenterol. 2014 Mar;48(3):300. doi: 10.1097/MCG.0b013e3182a8bfaf. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2021
• Primary Completion (Actual): May 1, 2022
• Study Completion (Actual): May 5, 2022

Study Registration Dates

• First Submitted: January 3, 2022
• First Submitted That Met QC Criteria: February 14, 2022
• First Posted (Actual): February 15, 2022

Study Record Updates

• Last Update Posted (Actual): May 10, 2022
• Last Update Submitted That Met QC Criteria: May 9, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Ascites; Paracentesis-Induced Circulatory Dysfunction; Paracentesis
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Adrenergic alpha-1 Receptor Agonists; Midodrine
• Other Study ID Numbers: AIGHEPAT007

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
• product manufactured in and exported from the U.S.: No