Evaluation of Low-dose Albumin and Midodrine Versus Midodrine Alone in Outcome of Recurrent Ascites in Patients With Decompensated Cirrhosis.

Evaluation of Low-dose Albumin and Midodrine Versus Midodrine Alone in Outcome of Recurrent Ascites in Patients With Decompensated Cirrhosis - An Open Label Multicentric Randomized Controlled Trial.

The project is about evaluation of albumin and midodrine versus midodrine alone in outcome of recurrent ascites in patients with decompensated cirrhosis.

Cirrhosis occcurs in 50% of patients over 10 years. The mortality is approximately 40% at 1 year and 50% at 2 years (12.7 per 100,000 population). A lot of times the prognosis is poor and the main factors leading to it are - acute kidney injury, hepatorenal syndrome, hyponatremia, grade of ascites-recurrent ascites, sarcopenia, low mean arterial pressure.

Post review of the literature, it is realized that there are some gap areas -

• It is unknown whether combination of vasoconstrictor with albumin versus vasoconstrictor alone is superior for ascites resolution in patients with recurrent ascites.
• There are no studies till date on using combination of vasoconstrictor with albumin versus vasoconstrictor alone in patients with recurrent ascites.
• There are no studies on impact of combining vasoconstrictor and albumin in preventing the development of AKI and chronic kidney disease in these patients.

In an effort to bridge these gap areas, this project works on the following hypothesis - "Midodrine would have a synergistic effect with albumin in improving the systemic hemodynamics and circulatory dysfunction and will cause rapid control of ascites, reduce the incidence of large volume paracentesis (LVP), complications, reduce the incidence of chronic kidney disease (HRS-CKD) and improve outcome of patients with recurrent ascites in patients with decompensated cirrhosis as compared to midodrine alone"

Primary objective: To assess the effect of midodrine alone vs. a combination of midodrine and albumin on the survival free of TIPS and liver transplant at 6 months

Secondary objective:

The effect of midodrine alone vs. combination of midodrine and albumin on the cumulative frequency of therapeutic paracentesis at 6 and 12 months Proportion of patients achieving control of ascites at 6 and 12 months

Study Overview

• Status: Not yet recruiting
• Conditions: Decompensated Cirrhosis
• Intervention / Treatment: Other: Standard of Care; Drug: Albumin; Drug: Midodrine

Detailed Description

• Study population: Consecutive patients with decompensated cirrhosis with recurrent ascites seen as inpatients or outpatients in the Department of Hepatology at Institute of Liver and Biliary Sciences, who meet the inclusion criteria and provide informed consent
• Study design: Multicentre Open-label Randomised Controlled Trial
• Sample Size: Assuming that survival rate with albumin and midodrine is 80%, whereas with midodrine alone is 50% (i.e. 30% absolute difference is observed with alpha of 5% power, beta of 80%) we need to enroll 43 cases in each arm and taking 15% drop out rate we need to enrol 50 cases in each group.
• Intervention: Group A will be treated with 20 grams/ week Albumin + Midodrine (5mg thrice daily and will be increased every 3 days upto 15 mg thrice daily with target MAP (>75 mm and <90) and Group B midodrine alone titrated based on MAP. Albumin infusions will be provided with large volume paracentesis and if the patient develops AKI, SBP in the recommended dosage in accordance to the International Club of ascites. The protocol will be followed for 6 months

Adverse effects: Allergic reactions to albumin, worsening of dyspnea, volume-overload

Stopping Rule: adverse reaction to Albumin

• Cardiopulmonary compromise
• Allergic reaction

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dr Rakhi Maiwall, DM; Phone Number: 01146300000; Email: rakhi_2011@yahoo.co.in

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of Liver & Biliary Sciences
      • Contact: Dr Rakhi Maiwall, DM; Phone Number: 01146300000; Email: rakhi_2011@yahoo.co.in
      • Principal Investigator: Dr Rakhi Maiwall, DM
  • Hyderabad
    • Somajiguda, Hyderabad, India, 500082
      • Asian institute of Gastroenterology
      • Contact: Dr Mithun Sharma, DM; Phone Number: 04023378888; Email: iecaig2044@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. 18 -70yr and Cirrhosis with recurrent ascites.

Exclusion Criteria:

1. Recent Gastrointestinal bleeding within 7 days
2. Systemic arterial hypertension (>160/90mmhg)
3. Presence of hepatocellular carcinoma or portal vein thrombosis, Budd-chiari syndrome.
4. Pregnancy
5. No use of drugs affecting systemic hemodynamics (excepting beta blockers) 7 days prior to enrolment.
6. Patients with Cardiovascular disease (NYHA > II) or chronic obstructive pulmonary disease
7. Refusal to participate
8. Known or suspected hypersensitivity to albumin
9. Prior TIPS
10. Post liver or kidney transplantation
11. Patients enrolled in other clinical trials
12. Extrahepatic malignancy
13. Patients on cardiac glycosides like digoxin, phenylephrine, ephedrine, thyroid hormones, ergot derivatives, salt retaining steroids like fludrocortisone, MAO inhibitors, alpha blockers metformin and ranitidine (known to have interactions with midodrine)
14. Patients with intrinsic kidney disease, organ nephropathy and CKD stage 4 and
15. MELD > 25 and extremely moribund patient
16. Serum albumin less than 2 gm/dl or >3.5 gm/dl
17. Significant ongoing alcohol with abstinence less than 3 months
18. Significant findings on ECHO with cardiac dysfunction

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
Experimental: Albumin + Midodrine; Albumin + Midodrine (5mg thrice daily and will be increased every 3 days upto 15 mg thrice daily with target MAP (>75 mm and <90).	Drug: Albumin; 20 grams/ week Albumin + Midodrine (5mg thrice daily and will be increased every 3 days upto 15 mg thrice daily with target MAP (>75 mm and <90).; Drug: Midodrine; Midodrine
Active Comparator: Midodrine +standard of care; Midodrine alone titrated based on MAP.	Other: Standard of Care; Standard of Care; Drug: Midodrine; Midodrine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Survival free of transplant and TIPS at 6 months.	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
The cumulative mean of the number of therapeutic paracentesis at 6 and 12 months would be compared between the two groups.	6 & 12 months
Proportion of patients achieving resolution of ascites (complete grade 1-0 without diuretics and partial as garde 0-1 ascites on diuretics)	6 & 12 months

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Estimated): February 10, 2024
• Primary Completion (Estimated): January 31, 2025
• Study Completion (Estimated): January 31, 2025

Study Registration Dates

• First Submitted: January 5, 2024
• First Submitted That Met QC Criteria: February 6, 2024
• First Posted (Estimated): February 7, 2024

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Ascites; 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: ILBS-Cirrhosis-58

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