Efficacy and Safety of Midodrine in Refractory or Recurrent Ascites in Children With Cirrhosis.
Status:
Recruiting
Trial end date:
2023-03-01
Target enrollment:
Participant gender:
Summary
Refractory ascites is seen in 17% of cirrhotic patients with the 1year mortality rate being
high, upto 20-50% [1]. The pathogenesis of cirrhotic ascites includes release of vasodilatory
molecules like nitric oxide, damage associated molecular pathogens (DAMPs) and pattern
associated molecular pathogens (PAMPs) secondary to bacterial translocation, which causes
splanchnic bed vasodilation resulting in activation of renin-angiotensin and aldosterone axis
causing sodium and water retention. The standard medical therapy for the treatment of ascites
includes sodium restriction to 2mEq/kg/day with diuretics (Spirinolactone 3-6mg/kg/day and
furosemide 0.5-2 mg/kg/day) and therapeutic paracentesis (>50ml/kg/day) with albumin
replacement at 8g/L of ascitic fluid tapped. Refractory ascites is defined as ascites that
cannot be mobilized by sodium - restricted diet (maximum upto 2mEq/kg/day- 88meq=2gm of salt)
and high-dose diuretic treatment (6 mg/kg/day of spironolactone and 2 mg/kg/day of
furosemide) or optimum doses of diuretics cannot be given due to development of
diuretic-induced complications (Sodium <130mEq, AKI as per KDIGO, hypovolemia, hypo
(<3.5meq)/hyperkalemia (>5meq); new onset HE) and recurrent ascites as ascites that has
recurred within a 12 weeks period despite standard treatment. All the children and
adolescents upto 18 years of age with refractory or recurrent ascites will be included in the
study and randomized into 2 groups. One group will receive only standard medical therapy and
other group will receive midodrine and standard medical therapy for 12 weeks. Mean arterial
pressure will be monitored at every OPD visit. At the end of 12 weeks, plasma renin activity,
number of therapeutic paracentesis done, change in serum sodium, estimated glomerular
filtration rate and complications will be assessed.
If there is complete resolution of ascites, liver transplantation or death before 12 weeks,
midodrine will be stopped.