Efficacy and Safety of Early Initiation of Midodrine for Control and Prevention of Ascites and Its Related Complications in Acute-on-chronic Liver Failure.

NCT07422948 | Not Yet Recruiting

• 1 other identifier: ILBS-ACLF-26
• Study Type: interventional
• Target: 113
• Locations: 1 country
• Sites: 1

Brief Summary

Ascites is a cardinal and debilitating complication in patients with acute-on-chronic liver failure (ACLF), significantly correlating with disease severity and poor prognosis. The underlying pathophysiology is driven by severe splanchnic arterial vasodilation, which reduces effective arterial blood volume and triggers compensatory neurohumoral activation. This cascade leads to profound sodium retention, renal vasoconstriction, and circulatory instability. Consequently, patients with ACLF frequently experience diuretic intolerance and are at elevated risk for severe complications, including electrolyte disturbances, acute kidney injury (AKI), and hepatorenal syndrome (HRS). Current management strategies rely heavily on diuretics and albumin; however, the efficacy of diuretics is often limited by systemic hypotension and pre-existing renal impairment, leading to frequent treatment failure or diuretic-induced complications. Existing clinical guidelines lack definitive recommendations regarding the preemptive use of vasoconstrictors to stabilize hemodynamics before ascites becomes refractory. Midodrine, an oral alpha-1 adrenergic agonist, targets this circulatory dysfunction by increasing systemic vascular resistance and improving renal perfusion. This randomized controlled trial aims to evaluate the efficacy and safety of the early initiation of midodrine in achieving better control of ascites and preventing the progression to renal complications in patients with acute-on-chronic liver failure.

Conditions

Acute on Chronic Liver Failure

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with no ascites between the two groups at day 28.

  Day 28

Secondary Outcomes (23)

• Percentage of patients with no ascites

  Day 7 & 14

• Partial ascites response

  7,14,28 days

• Absent response or worsening of ascites

  28 day

• Large Volume Paracentesis requirement in two groups

  day 7 and 28

• Cumulative dose of diuretics/Albumin/midodrine/carvedilol

  day 28

Study Arms (2)

Midodrine+SMT

EXPERIMENTAL

1. Sodium restriction to ≤5 g/day. 2. Combination of spironolactone 50 mg + furosemide 20 mg daily as a fixed dose. a) Stepwise titration every 3 days if tolerated, with careful monitoring for AKI, hyponatremia, encephalopathy. Dose reduction or discontinuation if diuretic-related complications develop. 3. Other supportive measures: as per the clinician 1. Lactulose ± rifaximin for hepatic encephalopathy prophylaxis/management. 2. IV albumin during LVP 3. Antibiotic prophylaxis/treatment as indicated for SBP or systemic infections. 4. Correction of electrolytes and renal support as needed. 5. Management of precipitating factors (alcohol, infection, flare of hepatitis, GI bleed, etc.). 4. Midodrine: Start with 5 mg TDS. Increase 2.5 mg every day with target MAP increase of 10 mmHg, maximum upto 15 mg TDS.

Drug: Midodrine; Other: Standard Medical Treatment

Placebo+SMT

ACTIVE COMPARATOR

1. Sodium restriction to ≤5 g/day. 2. Combination of spironolactone 50 mg + furosemide 20 mg daily as a fixed dose. a) Stepwise titration every 3 days if tolerated, with careful monitoring for AKI, hyponatremia, encephalopathy. Dose reduction or discontinuation if diuretic-related complications develop. 3. Other supportive measures: as per the clinician 1. Lactulose ± rifaximin for hepatic encephalopathy prophylaxis/management. 2. IV albumin during LVP 3. Antibiotic prophylaxis/treatment as indicated for SBP or systemic infections. 4. Correction of electrolytes and renal support as needed. 5. Management of precipitating factors (alcohol, infection, flare of hepatitis, GI bleed, etc.). 4. Placebo

Other: Standard Medical Treatment

Interventions

Midodrine DRUG

Start with 5 mg TDS. Increase 2.5 mg every day with target MAP increase of 10 mmHg, maximum upto 15 mg TDS.

Midodrine+SMT

Standard Medical Treatment OTHER

1. Sodium restriction to ≤5 g/day. 2. Combination of spironolactone 50 mg + furosemide 20 mg daily as a fixed dose. a) Stepwise titration every 3 days if tolerated, with careful monitoring for AKI, hyponatremia, encephalopathy. Dose reduction or discontinuation if diuretic-related complications develop. 3. Other supportive measures: as per the clinician 1. Lactulose ± rifaximin for hepatic encephalopathy prophylaxis/management. 2. IV albumin during LVP 3. Antibiotic prophylaxis/treatment as indicated for SBP or systemic infections. 4. Correction of electrolytes and renal support as needed. 5. Management of precipitating factors (alcohol, infection, flare of hepatitis, GI bleed, etc.).

Midodrine+SMT; Placebo+SMT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years.
• ACLF
• Ascites (Grade II/III).
• Willing/able for salt restriction, labs, urine collections, and follow-ups; consent obtained.

You may not qualify if:

• SCr ≥ 1.5 mg/dL OR ongoing AKI \>stage I
• Persistent or uncorrectable severe hyponatremia (Na ≤120 mEq/L), hyperkalemia (\>6.0 mEq/L) or any other critical electrolyte imbalance.
• Refractory ascites
• Spontaneous bacterial peritonitis
• Hepatic encephalopathy grade II-III.
• Shock, need for IV vasopressors, SBP \<90 mmHg or MAP \<65 despite fluids/albumin.
• Active GI bleed, uncontrolled infection/sepsis, or SBP at screening.
• Severe cardiomyopathy, critical valvular disease, arrhythmias contraindicating α-agonists.
• ACLF patients on Mechanical ventilation/ICU/ionotropes/High flow oxygen
• Pregnancy, lactation.
• Hypersensitivity/intolerance to midodrine.
• Significant LUTS.

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (1)

Institute of Liver and Biliary Sciences

New Delhi, National Capital Territory of Delhi, 110070, India

Location

MeSH Terms

Conditions

Acute-On-Chronic Liver Failure

Interventions

Midodrine

Condition Hierarchy (Ancestors)

Liver Failure, Acute; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Central Study Contacts

Dr Chunnee Zangmu Bhutia, MD

CONTACT

01146300000; czb.cr7@gmail.com

Dr Ankur S Jindal, DM

CONTACT

01146300000; ankur.jindal3@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2026
• First Posted: February 20, 2026
• Study Start: February 5, 2026
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): August 30, 2027
• Last Updated: February 20, 2026

Record last verified: 2026-01

Locations

IN (1)