NCT07422948

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

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

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 113 (estimated)
• Sponsor: Institute of Liver and Biliary Sciences, India · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
DRUG	Midodrine	Start with 5 mg TDS. Increase 2.5 mg every day with target MAP increase of 10 mmHg, maximum upto 15 mg TDS.
OTHER	Standard Medical Treatment	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.).

Timeline

• Start date: 2026-02-05
• Primary completion: 2027-08-30
• Completion: 2027-08-30
• First posted: 2026-02-20
• Last updated: 2026-02-20

Locations

1 site across 1 country: India