Clinical trial NCT05287100: To Assess the Efficacy of Midodrine in Prevention of Cirrhosis Related Complications in Children Awaiting Liver Transplantation.
Official title: To Assess the Efficacy of Midodrine in Prevention of Cirrhosis Related Complications in Children Awaiting Liver Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cirrhosis, Liver
Lead sponsor: Institute of Liver and Biliary Sciences, India
Sponsor class: OTHER
First posted: 2022-03-18
Enrollment: 35
Sex: ALL
Minimum age (years): 10
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

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

Primary Objective:

1) 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

Eligibility criteria: 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

Primary outcomes:
measure: Complications between the two groups
timeFrame: 6 months
Secondary outcomes:
measure: • Frequency of development of new onset ascites or increase in grade of ascites by 6 months
timeFrame: 6 months
measure: Change in serum sodium from baseline to 6 months
timeFrame: 6 months
measure: Change in Mean arterial pressure (MAP) at 1 week and then 2 weekly till the end of the study
timeFrame: 6 months
measure: Plasma renin activity at baseline, at 12 weeks and 24 weeks
timeFrame: 6 months
measure: Frequency of development of SBP over 6 months
timeFrame: 6 months
measure: Change in eGFR from baseline to 6 months
timeFrame: 6 months
measure: Frequency of developing AKI by 6 months
timeFrame: 6 months
measure: Frequency of development of Hepatic encephalopathy by 6 months
timeFrame: 6 months
measure: Proportion of patients developing hypertension at 6 months
timeFrame: 6 months
measure: Frequency of development of drug related adverse effects by 6 months
timeFrame: 6 months
measure: Requirement of albumin infusion in 2 groups
timeFrame: 6 months
measure: Transplant free survival
timeFrame: 6 months
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Institute of liver and biliary sciences
Study officials:
affiliation: ILBS
name: Prof. Seema Alam, MD
role: STUDY_DIRECTOR
References: