To Assess the Efficacy of Midodrine in Prevention of Cirrhosis Related Complications in Children Awaiting Liver Transplantation.

Summary

Children with cirrhosis awaiting transplantation are more proned to develop various complications. The pathogenesis of cirrhotic complications (ascites, hyponatremia, acute kidney injury) 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(RAAS) causing sodium and water retention and renal vasoconstriction \[1\].

The development of complications in these children may result in death or may preclude them from reaching upto liver transplantation \[2\].

Midodrine is an α1 adrenergic receptor agonist, which increases vascular tone causing rise in the blood pressure, thereby improving renal perfusion and causes RAAS deactivation. The effects of midodrine is documented in reduction of refractory ascites, hepatorenal syndrome and hyponatremia\[2-4\].

One group will receive only standard medical therapy and other group will receive midodrine and standard medical therapy for 6 months. Mean arterial pressure will be monitored at every OPD visit. At the end of 12 weeks, and 24 weeks, plasma renin activity, incidence of complications related to cirrhosis like new onset ascites, increase in grade of ascites, hyponatremia, acute kidney injury and spontaneous bacterial peritonitis will be assessed. Also the transplant free survival and need for albumin transfusion will be compared between the two groups.

In case of liver transplantation or death before 6 months, midodrine will be stopped

Conditions

• Cirrhosis, Liver

Interventions

DRUG

Midodrine Oral Tablet

Midodrine starting at 0.25mg/kg/day in 2-3 divided doses, increased to 0.5mg/kg/day after 7 days if MAP does not increase by \>10% ; Midodrine dosage will be decreased by 25% in case of arterial hypertension (\>95th centile BP for the age). Also Standard medical therapy as per departmental protocol will be continued

OTHER

Standard Medical Treatment

Albumin infusion 1g/kg/day - maximum 20gm/day and repeat till serum albumin reaches 2.8g/dl If serum albumin is \< 2.8g/dl SBP - Day 1 and Day 3 For Ascites : Restriction of sodium to \< 2meq/kg/day A combination of a distal-acting diuretic (spironolactone, 3-6 mg/ kg/day) and loop-acting diuretic (furosemide,0.5- 2 mg/kg per day) was given with dose escalation by one step at a time if there is no decrease in weight (by ≥ 0.5 %/day) after 5-7 days Therapeutic paracentesis (\>50ml/kg) with infusion of albumin (8 g/L) performed for tense, symptomatic ascites For Spontaneous Bacterial Peritonitis : IV antibiotics for 7 days Albumin Infusion on Day 1 and Day 3

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India

  lead OTHER

Principal Investigators

• Prof. Seema Alam, MD · ILBS

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

10 Days

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-01-01

Primary Completion

2023-05-30

Completion

2023-05-30

Countries

• India

Study Locations