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

Institute of Liver and Biliary Sciences, India

Status

Completed

Conditions

Cirrhosis, Liver

Treatments

Other: Standard Medical Treatment

Drug: Midodrine Oral Tablet

Study type

Interventional

Funder types

Other

Identifiers

NCT05287100

ILBS-Cirrhosis-49

Details and patient eligibility

About

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

Full description

Aim: To determine the efficacy of midodrine in preventing development of complications in children with cirrhosis awaiting liver transplantation

Primary Objective:

To compare incidence of complications (Acute kidney injury, New onset ascites or increase in grade of ascites, Spontaneous bacterial peritonitis, Hyponatremia, Hepatic encephalopathy) of cirrhosis in patients receiving midodrine (at a dose of 0.25 - 0.5mg/kg/day) and standard medical therapy versus standard medical therapy alone for 6 months

Secondary Objectives:

Frequency of development of new onset ascites or increase in grade of ascites by 6 months
Change in serum sodium from baseline to 6 months
Change in Mean arterial pressure (MAP) at 1 week and then 2 weekly till the end of the study
Plasma renin activity at baseline, at 12 weeks and 24 weeks
Frequency of development of SBP over 6 months
Change in eGFR from baseline to 6 months
Frequency of developing AKI by 6 months
Frequency of development of Hepatic encephalopathy by 6 months
Proportion of patients developing hypertension at 6 months
Frequency of development of drug related adverse effects by 6 months
Requirement of albumin infusion in 2 groups
Transplant free survival

Methodology:

Study population :Children and Adolescents of age group upto 18 years with cirrhosis and PELD/ MELDNa score more than 14, on waitlist for liver transplantation following up in the Pediatric Hepatology Department
Study design: Open label RCT (computer based randomization - block randomization with block size of 4)
Study period: 6 months weeks for each patient; The study will be conducted between January 2022 and July 2023
Sample size:
Pilot study - 10 patients in each group

Enrollment

35 patients

Sex

All

Ages

10 days to 18 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Children and Adolescents of age group upto 18 years with cirrhosis and PELD/ MELDNa score more than 14, on waitlist for liver transplantation following up in the Pediatric Hepatology Department, ILBS will be prospectively included in this study after informed consent

Exclusion criteria

Presence of Portal vein thrombosis Renal or cardiovascular disease or arterial hypertension Presence of HCC

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

35 participants in 2 patient groups

Midodrine

Experimental group

Description:

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

Treatment:

Other: Standard Medical Treatment

Drug: Midodrine Oral Tablet

Standard medical therapy

Active Comparator group

Description:

Standard medical therapy as per departmental protocol

Treatment:

Other: Standard Medical Treatment