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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
113
Start with 5 mg TDS. Increase 2.5 mg every day with target MAP increase of 10 mmHg, maximum upto 15 mg TDS.
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.).
Institute of Liver and Biliary Sciences
New Delhi, National Capital Territory of Delhi, India
Proportion of patients with no ascites between the two groups at day 28.
Time frame: Day 28
Percentage of patients with no ascites
Time frame: Day 7 & 14
Partial ascites response
Time frame: 7,14,28 days
Absent response or worsening of ascites
Time frame: 28 day
Large Volume Paracentesis requirement in two groups
Time frame: day 7 and 28
Cumulative dose of diuretics/Albumin/midodrine/carvedilol
Time frame: day 28
Change in Intra Abdominal pressure measured by manometer between both groups
Time frame: Day 7
Change in MAP between both groups.
Time frame: 7 days, then day 14 and 28
Change in Weight change between both groups.
Time frame: 7 days, then day 14 and 28
Change in urine output daily between both groups
Time frame: 7 days, then day 14 and 28
Change in HR between both groups
Time frame: 7 days, then day 14 and 28
Change in urine Na
Time frame: day 3, 7 and 28 from baseline
Change in MELD score between both groups.
Time frame: day 4, 7 and 28
Change in AARC score between both groups.
Time frame: day 4, 7 and 28
Reduction in Hepatic Venous Pressure Gradient between both groups.
Time frame: 14 and 28 days.
Mortality
Time frame: day 28
New onset AKI between both groups.
Time frame: day 28
New onset SBP between both groups
Time frame: day 28
New onset AKI, SBP, HE, Hyponatremia, shock and need for MV
Time frame: day 28
New onset HE between both groups
Time frame: day 28
New onset Hyponatremia between both groups.
Time frame: day 28
New onset shock between both groups.
Time frame: day 28
New onset need for MV between both groups
Time frame: day 28
Treatment related adverse effects
Time frame: day 28
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