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

Not Applicable

Not yet recruiting

• Conditions: Liver Cirrhosis
• Interventions: Drug: Midodrine; Biological: albumin; Other: Standard Medical Treatment

• Registration Number: NCT06091345
• Lead Sponsor: Institute of Liver and Biliary Sciences, India

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:

1. To compare the rate of control of ascites by 6 months in the 2 groups

2. 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

3. To compare the Plasma renin activity at baseline, 4 weeks, 3mo, 6mo in the 2 groups

4. Evaluate the change in serum sodium from baseline to 6 months in the 2 groups

5. To compare the Creatinine from baseline to 6 months in the 2 groups

6. To compare the Frequency of development of drug related adverse effects by 6 months

7. To compare the Transplant free survival in the 2 groups

8. To compare the Cytokines levels at baseline and 6 months in the 2 groups

9. 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.

Study Timeline

• Status Verified: 2023-10
• Study First Submitted: 2023-10-13
• Study First Submitted QC: 2023-10-13
• Last Update Submitted: 2023-10-13
• Study First Posted: 2023-10-19
• Last Update Posted: 2023-10-19
• Study Start: 2023-10-25
• Primary Completion: 2025-02-27
• Study Completion: 2025-02-27

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Children (≤ 18 years)
2. Cirrhosis based on histological/ radiological + endoscopic evidence
3. Clinical ascites (≥ grade 2 ascites)
4. Informed consent from parents (Assent > 12 years)

Exclusion Criteria

1. Arterial hypertension (Mean Arterial Pressure ≥ 95th centile for age)
2. Presence of Portal vein thrombosis
3. Hepatorenal Syndrome
4. Congestive Heart failure
5. Respiratory failure(PF ratio <200)
6. Septic shock
7. Presence of Hepatocellular Carcinoma
8. Transjugular intrahepatic Porto Systemic Shunt

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Midodrine+Albumin+SMT	albumin	* 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+Albumin+SMT	Standard Medical Treatment	* 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+SMT	Standard Medical Treatment	• 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+Albumin+SMT	Midodrine	* 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+SMT	Midodrine	• 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.

Primary Outcome Measures

Name	Time	Method
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.	6 months

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Institute of Liver & Biliary Sciences (ILBS); 🇮🇳 New Delhi, Delhi, India