Evaluation of Low-dose Albumin and Midodrine Versus Midodrine Alone in Outcome of Recurrent Ascites in Patients With Decompensated Cirrhosis.

Decompensated Cirrhosis Clinical Trial

Official title:

Evaluation of Low-dose Albumin and Midodrine Versus Midodrine Alone in Outcome of Recurrent Ascites in Patients With Decompensated Cirrhosis - An Open Label Multicentric Randomized Controlled Trial.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06245590
• Other study ID #: ILBS-Cirrhosis-58
• Status: Not yet recruiting
• Phase: N/A
• Start date: February 10, 2024
• Est. completion date: January 31, 2025

Study information

• Verified date: June 2023
• Source: Institute of Liver and Biliary Sciences, India
• Contact: Dr Rakhi Maiwall, DM
• Phone: 01146300000
• Email: rakhi_2011[@]yahoo.co.in
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The project is about evaluation of albumin and midodrine versus midodrine alone in outcome of recurrent ascites in patients with decompensated cirrhosis.

Cirrhosis occcurs in 50% of patients over 10 years. The mortality is approximately 40% at 1 year and 50% at 2 years (12.7 per 100,000 population). A lot of times the prognosis is poor and the main factors leading to it are - acute kidney injury, hepatorenal syndrome, hyponatremia, grade of ascites-recurrent ascites, sarcopenia, low mean arterial pressure.

Post review of the literature, it is realized that there are some gap areas -

• It is unknown whether combination of vasoconstrictor with albumin versus vasoconstrictor alone is superior for ascites resolution in patients with recurrent ascites.

• There are no studies till date on using combination of vasoconstrictor with albumin versus vasoconstrictor alone in patients with recurrent ascites.

• There are no studies on impact of combining vasoconstrictor and albumin in preventing the development of AKI and chronic kidney disease in these patients.

In an effort to bridge these gap areas, this project works on the following hypothesis - "Midodrine would have a synergistic effect with albumin in improving the systemic hemodynamics and circulatory dysfunction and will cause rapid control of ascites, reduce the incidence of large volume paracentesis (LVP), complications, reduce the incidence of chronic kidney disease (HRS-CKD) and improve outcome of patients with recurrent ascites in patients with decompensated cirrhosis as compared to midodrine alone"

Primary objective: To assess the effect of midodrine alone vs. a combination of midodrine and albumin on the survival free of TIPS and liver transplant at 6 months

Secondary objective:

The effect of midodrine alone vs. combination of midodrine and albumin on the cumulative frequency of therapeutic paracentesis at 6 and 12 months Proportion of patients achieving control of ascites at 6 and 12 months

Description:

• Study population: Consecutive patients with decompensated cirrhosis with recurrent ascites seen as inpatients or outpatients in the Department of Hepatology at Institute of Liver and Biliary Sciences, who meet the inclusion criteria and provide informed consent

• Study design: Multicentre Open-label Randomised Controlled Trial

• Sample Size: Assuming that survival rate with albumin and midodrine is 80%, whereas with midodrine alone is 50% (i.e. 30% absolute difference is observed with alpha of 5% power, beta of 80%) we need to enroll 43 cases in each arm and taking 15% drop out rate we need to enrol 50 cases in each group.

• Intervention: Group A will be treated with 20 grams/ week Albumin + Midodrine (5mg thrice daily and will be increased every 3 days upto 15 mg thrice daily with target MAP (>75 mm and <90) and Group B midodrine alone titrated based on MAP. Albumin infusions will be provided with large volume paracentesis and if the patient develops AKI, SBP in the recommended dosage in accordance to the International Club of ascites. The protocol will be followed for 6 months

Adverse effects: Allergic reactions to albumin, worsening of dyspnea, volume-overload

Stopping Rule: adverse reaction to Albumin

• Cardiopulmonary compromise

• Allergic reaction

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: January 31, 2025
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. 18 -70yr and Cirrhosis with recurrent ascites.

Exclusion Criteria:

1. Recent Gastrointestinal bleeding within 7 days

2. Systemic arterial hypertension (>160/90mmhg)

3. Presence of hepatocellular carcinoma or portal vein thrombosis, Budd-chiari syndrome.

4. Pregnancy

5. No use of drugs affecting systemic hemodynamics (excepting beta blockers) 7 days prior to enrolment.

6. Patients with Cardiovascular disease (NYHA > II) or chronic obstructive pulmonary disease

7. Refusal to participate

8. Known or suspected hypersensitivity to albumin

9. Prior TIPS

10. Post liver or kidney transplantation

11. Patients enrolled in other clinical trials

12. Extrahepatic malignancy

13. Patients on cardiac glycosides like digoxin, phenylephrine, ephedrine, thyroid hormones, ergot derivatives, salt retaining steroids like fludrocortisone, MAO inhibitors, alpha blockers metformin and ranitidine (known to have interactions with midodrine)

14. Patients with intrinsic kidney disease, organ nephropathy and CKD stage 4 and

15. MELD > 25 and extremely moribund patient

16. Serum albumin less than 2 gm/dl or >3.5 gm/dl

17. Significant ongoing alcohol with abstinence less than 3 months

18. Significant findings on ECHO with cardiac dysfunction

Related Conditions & MeSH terms

• Ascites
• Decompensated Cirrhosis
• Fibrosis
• Liver Cirrhosis

Intervention

Drug:
• Albumin
20 grams/ week Albumin + Midodrine (5mg thrice daily and will be increased every 3 days upto 15 mg thrice daily with target MAP (>75 mm and <90).
• Midodrine
Midodrine

Other:
• Standard of Care
Standard of Care

Locations

Country	Name	City	State
India	Institute of Liver & Biliary Sciences	New Delhi	Delhi
India	Asian Institute of Gastroenterology	Somajiguda	Hyderabad

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Liver and Biliary Sciences, India

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival free of transplant and TIPS at 6 months.		6 months
Secondary	The cumulative mean of the number of therapeutic paracentesis at 6 and 12 months would be compared between the two groups.		6 & 12 months
Secondary	Proportion of patients achieving resolution of ascites (complete grade 1-0 without diuretics and partial as garde 0-1 ascites on diuretics)		6 & 12 months