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

NCT05287100 | Completed

• 1 other identifier: ILBS-Cirrhosis-49
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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

Conditions

Cirrhosis, Liver

Outcome Measures

Primary Outcomes (1)

• Complications between the two groups

  • 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

  6 months

Secondary Outcomes (12)

• • Frequency of development of new onset ascites or increase in grade of ascites by 6 months

  6 months

• Change in serum sodium from baseline to 6 months

  6 months

• Change in Mean arterial pressure (MAP) at 1 week and then 2 weekly till the end of the study

  6 months

• Plasma renin activity at baseline, at 12 weeks and 24 weeks

  6 months

• Frequency of development of SBP over 6 months

  6 months

Study Arms (2)

Midodrine

EXPERIMENTAL

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

Drug: Midodrine Oral Tablet; Other: Standard Medical Treatment

Standard medical therapy

ACTIVE COMPARATOR

Standard medical therapy as per departmental protocol

Other: Standard Medical Treatment

Interventions

Midodrine Oral Tablet DRUG

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

Midodrine

Standard Medical Treatment OTHER

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

Midodrine; Standard medical therapy

Eligibility Criteria

• Age: 10 Days - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Institute of Liver and Biliary Sciences, India: lead

Study Sites (1)

Institute of liver and biliary sciences

New Delhi, 110070, India

Location

Related Publications (1)

• Ashritha A, Lal BB, Khanna R, Sood V, Sood AK, Alam S. Midodrine reduces new-onset acute kidney injury and hyponatremia in children with cirrhosis and ascites awaiting liver transplantation: Results from an open-label RCT. J Pediatr Gastroenterol Nutr. 2024 Feb;78(2):350-359. doi: 10.1002/jpn3.12077. Epub 2023 Dec 11.

  PMID: 38374552 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

Midodrine

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Study Officials

• Prof. Seema Alam, MD

  ILBS

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2022
• First Posted: March 18, 2022
• Study Start: January 1, 2022
• Primary Completion: May 30, 2023
• Study Completion: May 30, 2023
• Last Updated: October 10, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)