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

Официальное название

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.

Обзор

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.

Вмешательства

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

Первичные конечные точки

• Proportion of patients with no ascites between the two groups at day 28. [Срок оценки: Day 28]

Вторичные конечные точки (12)

• Percentage of patients with no ascites [Срок оценки: Day 7 & 14]
• Partial ascites response [Срок оценки: 7,14,28 days]
• Absent response or worsening of ascites [Срок оценки: 28 day]
• Large Volume Paracentesis requirement in two groups [Срок оценки: day 7 and 28]
• Cumulative dose of diuretics/Albumin/midodrine/carvedilol [Срок оценки: day 28]
• Change in Intra Abdominal pressure measured by manometer between both groups [Срок оценки: Day 7]
• Change in MAP between both groups. [Срок оценки: 7 days, then day 14 and 28]
• Change in Weight change between both groups. [Срок оценки: 7 days, then day 14 and 28]
• Change in urine output daily between both groups [Срок оценки: 7 days, then day 14 and 28]
• Change in HR between both groups [Срок оценки: 7 days, then day 14 and 28]
• Change in urine Na [Срок оценки: day 3, 7 and 28 from baseline]
• Change in MELD score between both groups. [Срок оценки: day 4, 7 and 28]

Критерии участия

Критерии включения

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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Индия · 1 центр

• Institute of Liver and Biliary Sciences — New Delhi

Идентификаторы

NCT: NCT07422948 · ILBS-ACLF-26

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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