Evaluation of Albumin and Midodrine Versus Albumin Alone in Outcome of Refractory Ascites in Patients With Decompensated Cirrhosis.

Evaluation of Albumin and Midodrine Versus Albumin Alone in Outcome of Refractory Ascites in Patients With Decompensated Cirrhosis - A Double Blind Randomized Controlled Trial."

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

Cirrhosis is a leading cause of disability and mortality worldwide. Cirrhosis occurs in 50% of patients over 10 years. Decompensated cirrhosis carries a poor prognosis because the median survival time is about 2 years and it imposes a heavy burden on health care costs mainly due to the need for repeated hospital admission. 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 - AKI/HRS-NAKI, Hyponatremia, Grade of ascites-Refractory 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 further decreases the need for paracentesis in patients of refractory ascites.
• There are no studies till date on using combination of vasoconstrictor with albumin for refractory ascites.
• There are no studies evaluating the prevalence and incidence of HRS-NAKI using the new definitions in patients with refractory ascites and impact of combining vasoconstrictor and albumin in improving renal outcomes in these patients.

Study Overview

• Status: Recruiting
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Other: Placebo; Other: Standard Medical Treatment; Drug: Midodrine; Biological: Albumin

Detailed Description

Study population All patients with decompensated cirrhosis with refractory ascites who get admitted under the Department of Hepatology at Institute of Liver and Biliary Sciences, who fulfilthe inclusion criteria, exclusion criteria and provide informed consent

• Study design Single Centre Placebo Controlled an open level Randomised Controlled Trial
• Study period 1 year from ethics approval.
• Sample size Assuming that survival rate with albumin and midodrine is 80%, whereas with albumin alone is 60% ( ie. 20% absolute difference is observed with alpha of 5% power so we need to enroll 170 cases allotted in 2 groups further taking 10% as dropout rate. It was decided to enroll 200 cases allotted in 2 groups randomly by block randomization method taking block size as 10
• Intervention Group A will be treated with SMT + 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 with SMT + Albumin: 80grams/week for 2 weeks followed by 40gram/week + Placebo

Stopping ruleAdverse reaction to Albumin

• Cardiopulmonary compromise
• Allergic reaction

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dr Priti Gupta, MD; Phone Number: 01146300000; Email: priti7vns@gmail.com

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Recruiting
      • Institute of Liver & Biliary Sciences
      • Contact: Dr Priti Gupta, MD; Phone Number: 01146300000; Email: priti7vns@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- Cirrhosis with refractory ascites

Exclusion Criteria:

- Recent Gastrointestinal bleeding within 7 days

• Systemic arterial hypertension (>160/90mmhg)
• Presence of hepatocellular carcinoma or portal vein thrombosis, Budd-chiari syndrome.
• Pregnancy
• No use of drugs affecting systemic hemodynamics 7 days prior to enrolment
• Patients with Cardiovascular disease (NYHA > II) or chronic obstructive pulmonary disease
• Refusal to participate
• Known or suspected hypersensitivity to albumin
• Prior TIPS
• Post liver or kidney transplantation
• Patients enrolled in other clinical trials
• Extrahepatic malignancy
• 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)
• Patients with intrinsic kidney disease, organ nephropathy and CKD stage 4 and
• MELD > 30 and extremely moribend patient

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Midodrine + Albumin +Standard Medical Treatment; SMT + Albumin + Midodrine (5mg thrice daily and will be increased every 3 days upto 15 mg thrice daily with target MAP (>75 mm and <90).	Other: Standard Medical Treatment; Standard Medical Treatment; Drug: Midodrine; 5mg thrice daily and will be increased every 3 days upto 15 mg thrice daily with target MAP (>75 mm and <90); Biological: Albumin; 80grams/week for 2 weeks followed by 40gram/week
Active Comparator: Albumin + Standard Medical Treatment+ Placebo; 80grams/week for 2 weeks followed by 40gram/week + Placebo	Other: Placebo; Placebo; Other: Standard Medical Treatment; Standard Medical Treatment; Biological: Albumin; 80grams/week for 2 weeks followed by 40gram/week

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of liver-related complications		3 months
Cumulative incidence of liver-related complications		6 months
Cumulative incidence of liver-related complications		12 months
Survival free of liver transplant in both groups		1 year
Survival free of TIPS in both groups		1 year
Incidence of HRS-AKD, in both groups at 1 year		1 year
Incidence of HRS-CKD in both groups at 1 year		1 year
Incidence of HRS AKI in both groups at 1 year		1 year
Cumulative frequency of large volume paracentesis		3 months
Cumulative frequency of large volume paracentesis		6 months
Cumulative frequency of large volume paracentesis		12 months
Improvement in fraility	AS PER MAYO FRAITITY INDEX , FRAITILY IS CLASSIFIED AS PRE FRAIL, FRAIL AND ROBUST.	3 months
Improvement in fraility	AS PER MAYO FRAITITY INDEX , FRAITILY IS CLASSIFIED AS PRE FRAIL, FRAIL AND ROBUST.	6 months
Improvement in fraility	AS PER MAYO FRAITITY INDEX , FRAITILY IS CLASSIFIED AS PRE FRAIL, FRAIL AND ROBUST.	12 months
Survival free of TIPS		6 months
Survival free of transplant at 6 months		6 months

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2021
• Primary Completion (Anticipated): March 19, 2022
• Study Completion (Anticipated): March 19, 2022

Study Registration Dates

• First Submitted: March 15, 2021
• First Submitted That Met QC Criteria: March 24, 2021
• First Posted (Actual): March 25, 2021

Study Record Updates

• Last Update Posted (Actual): June 15, 2021
• Last Update Submitted That Met QC Criteria: June 12, 2021
• Last Verified: March 1, 2021

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-40

Drug and device information, study documents

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