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.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 113
- 试验地点
- 1
- 主要终点
- Proportion of patients with no ascites between the two groups at day 28.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years.
- •Ascites (Grade II/III).
- •Willing/able for salt restriction, labs, urine collections, and follow-ups; consent obtained.
排除标准
- •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.
研究组 & 干预措施
Midodrine+SMT
- Sodium restriction to ≤5 g/day.
- 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
- Lactulose ± rifaximin for hepatic encephalopathy prophylaxis/management.
- IV albumin during LVP
- Antibiotic prophylaxis/treatment as indicated for SBP or systemic infections.
- Correction of electrolytes and renal support as needed.
- Management of precipitating factors (alcohol, infection, flare of hepatitis, GI bleed, etc.).
- Midodrine: Start with 5 mg TDS. Increase 2.5 mg every day with target MAP increase of 10 mmHg, maximum upto 15 mg TDS.
干预措施: Midodrine (Drug)
Midodrine+SMT
- Sodium restriction to ≤5 g/day.
- 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
- Lactulose ± rifaximin for hepatic encephalopathy prophylaxis/management.
- IV albumin during LVP
- Antibiotic prophylaxis/treatment as indicated for SBP or systemic infections.
- Correction of electrolytes and renal support as needed.
- Management of precipitating factors (alcohol, infection, flare of hepatitis, GI bleed, etc.).
- Midodrine: Start with 5 mg TDS. Increase 2.5 mg every day with target MAP increase of 10 mmHg, maximum upto 15 mg TDS.
干预措施: Standard Medical Treatment (Other)
Placebo+SMT
- Sodium restriction to ≤5 g/day.
- 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
- Lactulose ± rifaximin for hepatic encephalopathy prophylaxis/management.
- IV albumin during LVP
- Antibiotic prophylaxis/treatment as indicated for SBP or systemic infections.
- Correction of electrolytes and renal support as needed.
- Management of precipitating factors (alcohol, infection, flare of hepatitis, GI bleed, etc.).
- Placebo
干预措施: Standard Medical Treatment (Other)
结局指标
主要结局
Proportion of patients with no ascites between the two groups at day 28.
时间窗: Day 28
次要结局
- 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)
- Change in Intra Abdominal pressure measured by manometer between both groups(Day 7)
- Change in MAP between both groups.(7 days, then day 14 and 28)
- Change in Weight change between both groups.(7 days, then day 14 and 28)
- Change in urine output daily between both groups(7 days, then day 14 and 28)
- Change in HR between both groups(7 days, then day 14 and 28)
- Change in urine Na(day 3, 7 and 28 from baseline)
- Change in MELD score between both groups.(day 4, 7 and 28)
- Change in AARC score between both groups.(day 4, 7 and 28)
- Reduction in Hepatic Venous Pressure Gradient between both groups.(14 and 28 days.)
- Mortality(day 28)
- New onset AKI between both groups.(day 28)
- New onset SBP between both groups(day 28)
- New onset AKI, SBP, HE, Hyponatremia, shock and need for MV(day 28)
- New onset HE between both groups(day 28)
- New onset Hyponatremia between both groups.(day 28)
- New onset shock between both groups.(day 28)
- New onset need for MV between both groups(day 28)
- Treatment related adverse effects(day 28)