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Midodrine Plus Albumin Versus Midodrine Alone to Prevent Cirrhosis Related Complications in Children With Cirrhosis and Ascites

Primary Purpose

Liver Cirrhosis

Status
Not yet recruiting
Phase
Not Applicable
Locations
India
Study Type
Interventional
Intervention
Midodrine
albumin
Standard Medical Treatment
Sponsored by
Institute of Liver and Biliary Sciences, India
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Cirrhosis

Eligibility Criteria

12 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Children (≤ 18 years) Cirrhosis based on histological/ radiological + endoscopic evidence Clinical ascites (≥ grade 2 ascites) Informed consent from parents (Assent > 12 years) Exclusion Criteria: Arterial hypertension (Mean Arterial Pressure ≥ 95th centile for age) Presence of Portal vein thrombosis Hepatorenal Syndrome Congestive Heart failure Respiratory failure(PF ratio <200) Septic shock Presence of Hepatocellular Carcinoma Transjugular intrahepatic Porto Systemic Shunt

Sites / Locations

  • Institute of Liver & Biliary Sciences (ILBS)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Midodrine+Albumin+SMT

Midodrine+SMT

Arm Description

Albumin infusion 1g/kg/day (max 20g) every two weeks (if pre-infusion serum albumin is < 3.5 gm/dl Plus 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% . In addition, standard medical therapy will be administered to patients in both the arms.

• 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% In addition, standard medical therapy will be administered to patients in both the arms.

Outcomes

Primary Outcome Measures

To compare difference in composite incidence of complications of cirrhosis (Acute kidney injury, ascites, hyponatremia, hepatic encephalopathy) in patients receiving midodrine and albumin versus those receiving midodrine alone.

Secondary Outcome Measures

To compare the rate of control of ascites by 6 months in the 2 groups
To compare the change in Mean arterial pressure (MAP) at 1 week, 2 weeks, 4 weeks, 3 months, and 6 months in the 2 groups
To compare the Plasma renin activity at baseline, 4 weeks, 3mo, 6mo in the 2 groups
Evaluate the change in serum sodium from baseline to 6 months in the 2 groups
To compare the Creatinine from baseline to 6 months in the 2 groups
To compare the Frequency of development of drug related adverse effects by 6 months
To compare the Transplant free survival in the 2 groups
To compare the Cytokines levels at baseline and 6 months in the 2 groups
To compare the presence of Minimal Hepatic encephalopathy in the 2 groups

Full Information

First Posted
October 13, 2023
Last Updated
October 13, 2023
Sponsor
Institute of Liver and Biliary Sciences, India
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1. Study Identification

Unique Protocol Identification Number
NCT06091345
Brief Title
Midodrine Plus Albumin Versus Midodrine Alone to Prevent Cirrhosis Related Complications in Children With Cirrhosis and Ascites
Official Title
Midodrine Plus Albumin Versus Midodrine Alone to Prevent Cirrhosis Related Complications in Children With Cirrhosis and Ascites - An Open Label Randomized Controlled Trial.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 25, 2023 (Anticipated)
Primary Completion Date
February 27, 2025 (Anticipated)
Study Completion Date
February 27, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institute of Liver and Biliary Sciences, India

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Children with decompensated cirrhosis are more prone 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. The development of complications in these children may result in death or may preclude them from reaching upto liver transplantation. 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. Albumin is a protien that works by both increasing the colloidal oncotic pressure and improving systemic circulation as well as by effecting the body with anti-inflammatory and antioxidant properties. We have already demonstrated the safety and efficacy of midodrine as well as albumin in cirrhotic children. However, none of these drugs alone provided survival benefit to the patients. Hence, we have planned this study with the ojective to evaluate if combining these 2 drugs (midodrine and albumin) would further reduce the complications and improve the survival in decompensated cirrhotic children.
Detailed Description
Aim: To evaluate whether a combination of midodrine and intravenous albumin reduces complications of cirrhosis in decompensated (ascites) cirrhotic children as compared to midodrine alone. Primary objective: To compare difference in composite incidence of complications of cirrhosis (Acute kidney injury, ascites, hyponatremia, hepatic encephalopathy) in patients receiving midodrine and albumin versus those receiving midodrine alone. Secondary objectives: To compare the rate of control of ascites by 6 months in the 2 groups To compare the change in Mean arterial pressure (MAP) at 1 week, 2 weeks, 4 weeks, 3 months, and 6 months in the 2 groups To compare the Plasma renin activity at baseline, 4 weeks, 3mo, 6mo in the 2 groups Evaluate the change in serum sodium from baseline to 6 months in the 2 groups To compare the Creatinine from baseline to 6 months in the 2 groups To compare the Frequency of development of drug related adverse effects by 6 months To compare the Transplant free survival in the 2 groups To compare the Cytokines levels at baseline and 6 months in the 2 groups To compare the presence of Minimal Hepatic encephalopathy in the 2 groups Study population :Children and Adolescents of age group upto 18 years with decompensated cirrhosis with clinical ascites, following up in the Pediatric Hepatology Department, ILBS will be prospectively included in this study after informed consent Study design: Open-label Randomized Controlled Trial Study period: 6 months weeks for each patient; The study will be conducted from the time of ethical approval to June 2025. Sample size: In a pilot trial done at our center comparing midodrine and SMT the composite incidence of complication was 61.2% in midodrine arm. In absence of a pediatric study we assume a 25% reduction of complication by adding albumin along with midodrine keeping a power of study 80% , the sample size was calculated to be 30 in each arm.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cirrhosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Midodrine+Albumin+SMT
Arm Type
Experimental
Arm Description
Albumin infusion 1g/kg/day (max 20g) every two weeks (if pre-infusion serum albumin is < 3.5 gm/dl Plus 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% . In addition, standard medical therapy will be administered to patients in both the arms.
Arm Title
Midodrine+SMT
Arm Type
Active Comparator
Arm Description
• 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% In addition, standard medical therapy will be administered to patients in both the arms.
Intervention Type
Drug
Intervention Name(s)
Midodrine
Intervention Description
• 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%
Intervention Type
Biological
Intervention Name(s)
albumin
Intervention Description
• Albumin infusion 1g/kg/day (max 20g) every two weeks (if pre-infusion serum albumin is < 3.5 gm/dl
Intervention Type
Other
Intervention Name(s)
Standard Medical Treatment
Intervention Description
Standard Medical Treatment
Primary Outcome Measure Information:
Title
To compare difference in composite incidence of complications of cirrhosis (Acute kidney injury, ascites, hyponatremia, hepatic encephalopathy) in patients receiving midodrine and albumin versus those receiving midodrine alone.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
To compare the rate of control of ascites by 6 months in the 2 groups
Time Frame
6 months
Title
To compare the change in Mean arterial pressure (MAP) at 1 week, 2 weeks, 4 weeks, 3 months, and 6 months in the 2 groups
Time Frame
1 week, 2 weeks, 4 weeks, 3 months, and 6 months
Title
To compare the Plasma renin activity at baseline, 4 weeks, 3mo, 6mo in the 2 groups
Time Frame
baseline, 4 weeks, 3months, 6months
Title
Evaluate the change in serum sodium from baseline to 6 months in the 2 groups
Time Frame
6 months
Title
To compare the Creatinine from baseline to 6 months in the 2 groups
Time Frame
6 months
Title
To compare the Frequency of development of drug related adverse effects by 6 months
Time Frame
6 months
Title
To compare the Transplant free survival in the 2 groups
Time Frame
6 months
Title
To compare the Cytokines levels at baseline and 6 months in the 2 groups
Time Frame
6 months
Title
To compare the presence of Minimal Hepatic encephalopathy in the 2 groups
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Children (≤ 18 years) Cirrhosis based on histological/ radiological + endoscopic evidence Clinical ascites (≥ grade 2 ascites) Informed consent from parents (Assent > 12 years) Exclusion Criteria: Arterial hypertension (Mean Arterial Pressure ≥ 95th centile for age) Presence of Portal vein thrombosis Hepatorenal Syndrome Congestive Heart failure Respiratory failure(PF ratio <200) Septic shock Presence of Hepatocellular Carcinoma Transjugular intrahepatic Porto Systemic Shunt
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dr Samannay Das, MD
Phone
01146300000
Email
rimon100393@gmail.com
Facility Information:
Facility Name
Institute of Liver & Biliary Sciences (ILBS)
City
New Delhi
State/Province
Delhi
ZIP/Postal Code
110 070
Country
India
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Samannay Das, MD
Phone
01146300000
Email
rimon100393@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
No

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Midodrine Plus Albumin Versus Midodrine Alone to Prevent Cirrhosis Related Complications in Children With Cirrhosis and Ascites

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