Clinical trial NCT06245590: Evaluation of Low-dose Albumin and Midodrine Versus Midodrine Alone in Outcome of Recurrent Ascites in Patients With Decompensated Cirrhosis.
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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Decompensated Cirrhosis
Lead sponsor: Institute of Liver and Biliary Sciences, India
Sponsor class: OTHER
First posted: 2024-02-07
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Survival free of transplant and TIPS at 6 months.
timeFrame: 6 months
Secondary outcomes:
measure: The cumulative mean of the number of therapeutic paracentesis at 6 and 12 months would be compared between the two groups.
timeFrame: 6 & 12 months
measure: Proportion of patients achieving resolution of ascites (complete grade 1-0 without diuretics and partial as garde 0-1 ascites on diuretics)
timeFrame: 6 & 12 months
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Institute of Liver & Biliary Sciences
state: Delhi
city: Somajiguda
country: India
facility: Asian Institute of Gastroenterology
state: Hyderabad
Study officials:
References: