Albumin in Acute Variceal Bleeding

Albumin in acute variceal bleeding: A randomized controlled trial: ALB-AVB Trial

Introduction:

Albumin has been found to reduce mortality in patients with acute variceal bleeding in retrospective trials. However, there is no prospective data on this issue. We aim to conduct a randomized controlled trial on the role of albumin in patients with acute variceal bleeding.

Review of the literature Acute variceal bleeding is an important decompensating event in patients with cirrhosis. It is associated with 20-30% mortality in six weeks. Standard therapy with splanchnic vasoconstrictors and endoscopic band ligation is the mainstay of treatment. Previous studies have shown that albumin may decrease the mortality and re-bleeding rate in patients with AVB, however, there is no prospective data on this.

Apart from its oncotic properties albumin has different pleiotropic effects in patients with cirrhosis. It is an anti-oxidant and also binds to cytokines. Its anti-inflammatory property is responsible for reducing portal pressure and the risk of rebleeding. Currently, albumin is used in patients with acute kidney injury, spontaneous bacterial peritonitis and during large-volume paracentesis. There is also a theoretical risk of an increase in portal pressure in patients receiving albumin. The role of albumin in AVB is largely unknown. The current recommendation does not support its use in AVB however there is no strong evidence against it too. Currently, albumin has been shown to decrease mortality and decompensation in patients with cirrhosis. Large retrospective data from China have shown that albumin infusion is associated with reduced risk of rebleeding and mortality. In that study IV albumin of 40 grams/ day was associated with reduced mortality in patients with CTP-C cirrhosis. A perfectly designed RCT is warranted to explore the role of albumin in ABV.

Aim of the study:

To explore the role of albumin in patients with AVB. Study Methodology: It will be a randomised controlled trial conducted in the department of gastroenterology, KGMU Study Centre: Department of Gastroenterology, King George Medical University Lucknow Duration of the study: 6 months after the ethical approval

Sample Size Calculation:

Primary Outcome:

The primary endpoint is re-bleeding during hospitalization and at 6 weeks.

Standard Statistical Assumptions:

Expected re-bleeding rate in the control group (no albumin): 30% Expected reduction with intervention (albumin): 15% Significance level (α): 0.05 Power (1-β): 0.8

Formula for Binary Outcomes (Re-bleeding or No Re-bleeding):

n=(〖〖(Z〗_(∝/2)+Z_β)〗^2×[p_1 (1-p_1 )+p_2 (1-p_2 )])/(p_1-p_2 )^2

Where:

p1=0.30 (control event rate) p2=0.15 (intervention event rate) Zα/2=1.96 (for 95% confidence) Zβ=0.84 (for 80% power) Adding an attrition of minimum to 5% (0.05), the sample size for study obtained was that of 126 patients that is 63 patients in each arm. But for feasibility purposes it was rounded off to achieve a final sample size of 60 patients randomly allocated in each arm.

Inclusion criteria

• All adult patients with acute variceal bleeding and cirrhosis presenting to Medical Gastroenterology department at KGMU, Lucknow, U.P. India.

Exclusion criteria

• Age < 18 years and > 70 years
• Patients with portal vein thrombosis
• Hepatocellular carcinoma
• Non-cirrhotic portal fibrosis
• Extrahepatic portal vein thrombosis
• Patients who received albumin in the last one month
• Patients who require fresh frozen plasma
• Patients with heart failure
• Patients with chronic kidney disease
• Volume overload state