Efficacy and Safety of Midodrine in Refractory or Recurrent Ascites in Children With Cirrhosis.

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.

Conditions

• Refractory Ascites in Children With Cirrhosis

Interventions

DRUG

Midodrine

Midodrine starting at 0.25mg/kg/day in divided doses, increased to 0.5mg/kg/day after 7 days if MAP does not increase by \>10% (maximum dose - 15mg/day) • Midodrine dosage will be decreased by 25% in case of arterial hypertension (\>95th centile BP for the age)

OTHER

Standard medical treatment

Standard Medical Treatment will be continued in all, which includes, * To continue restriction of sodium to \< 2meq/kg/day * To continue maximum tolerable dose of diuretics * Repeat LVP with infusion of albumin (8 g/L) performed for tense, symptomatic ascites * Albumin infusion for serum albumin \<2.5g/dl - dose 1g/kg/day (maximum 20g/day)

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

6 Months

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-11-01

Primary Completion

2023-02-28

Completion

2023-03-31

Countries

• India

Study Locations