Efficacy and Safety of Early Initiation of Midodrine for Control and Prevention of Ascites and Its Related Complications in Acute-on-chronic Liver Failure.
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Midodrine, Standard Medical Treatment.
- Who it may be relevant to
- Registry conditions: Acute on Chronic Liver Failure. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- India
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
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.
Overview
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.
Interventions
- 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/tre
Primary outcome measures
- Proportion of patients with no ascites between the two groups at day 28. [Time frame: Day 28]
Secondary outcome measures (12)
- 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]
Eligibility criteria
Inclusion criteria
- Age ≥18 years.
- ACLF
- Ascites (Grade II/III).
- Willing/able for salt restriction, labs, urine collections, and follow-ups; consent obtained.
Exclusion criteria
- 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
India · 1 center
- Institute of Liver and Biliary Sciences — New Delhi
Identifiers
NCT: NCT07422948 · ILBS-ACLF-26