Efficacy of Conventional Dose Protocol vs Low Dose Protocol Albumin Use in Patients With Cirrhosis and High Risk Spontaneous Bacterial Peritonitis

The role of Albumin in prevention and Treatment of Acute Kidney Injury (AKI) in patients with Spontaneous Bacterial Peritonitis (SBP) who are at high risk of AKI development has been clearly defined, which decreases the morbidity and mortality. However the conventional dose recommended by the guidelines is usually not tolerated by the Indian population. Investigator propose that the low dose is as beneficial as the standard dose in patients with high risk SBP in the prevention/progression of renal dysfunction in cirrhotic patients with high risk spontaneous bacterial peritonitis. If confirmed, these results could support a significant cost reduction in the management of ascites in cirrhotic patients and decrease the side effects of the volume overload in the patient of the cirrhosis.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Cirrhosis; Spontaneous Bacterial Peritonitis
• Intervention / Treatment: Other: Standard Medical Treatment; Biological: 20% High Dose Albumin; Biological: 20% Reduced Dose Albumin

Detailed Description

Hypothesis Alternate Hypothesis: Low dose albumin is as effective as conventional dose albumin in cirrhosis with high risk SBP patients having AKI development or progression by day 4.

Aim:-To compare the efficacy and safety of low dose albumin with conventional dose albumin in AKI development or progression in patients with cirrhosis and high risk spontaneous bacterial peritonitis.

Study population: Patients of age > 18 years of age with cirrhosis of liver who are admitted in ward/ICU diagnosed with high risk SBP.

Study design: Randomized controlled trial Study period:1.5year Sample size: 300 (150 cases in each group) Assuming that the rate of AKI development in conventional dose albumin group - 10% and low dose albumin group 15%, Power- 80%, Alpha- 10% ONE SIDED, Non inferiority limit- 5, cases needed to enroll are 270, further assuming 10% dropout, investigator decided to enroll total 300 cases, randomly allocated with 150 cases in each arm by block randomization method with Block size of 10 Cases will be randomly allocated in 2 groups by block randomization method with block size taken as 10.

STATISTICAL ANALYSIS:

Continuous variables- Mean +/- SD Categorical variables as percentages (%) or Frequencies Student t test will be applied in continuous data compared with two groups Survival analysis like Cox-Regression model and Kaplan-Meir plots will be plotted to find the possible factors responsible for mortality Besides these, Intent to treat (ITT) and Per Protocol (PP) will be done at the time of data analysis.

Adverse effects:

Patients receiving Albumin may experience Nausea, Vomiting, Fever with chills, dyspnea Wheezing, Volume overload, Anaphylactic reaction

Stopping rule of study:

Adverse reaction to drug Cardiopulmonary compromise

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dr Sourav Paul, MD; Phone Number: 01146300000; Email: saurav.paul79@gmail.com

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of Liver & Biliary Sciences
      • Contact: Dr Saurabh Paul, MD; Phone Number: 01146300000; Email: saurav.paul79@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age >18years
2. Cirrhosis with SBP (community acquired /Health care associated/ nosocomial)
3. High risk SBP : Patients with S Bil >4 mg/dL and/or s creat > 1 mg/dl at presentation

Exclusion Criteria:

1. Antibiotic treatment within one week before the diagnosis of SBP (except for prophylactic treatment with norfloxacin)
2. Significant cardiac failure, pulmonary disease
3. Known CKD or findings suggestive of organic nephropathy (proteinuria, haematuria, or abnormal findings on renal USG)
4. Hepatocellular carcinoma
5. HIV infection
6. GI bleed within 1 month before the study
7. Grade 3 to 4 hepatic encephalopathy
8. Shock (MAP < 65)
9. Serum creatinine level of > 3 mg/decilitre
10. Presence of any potential causes of dehydration (such as diarrhea or an intense response to diuretic treatment within one week before the diagnosis of SBP).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High Dose Arm; Human Albumin 20% 1.5 g/kg body weight (Maximum 100g) on day 1 after the diagnosis, followed by 1 g/kg body weight (Maximum 100g)on day 3 along with standard medical therapy.	Other: Standard Medical Treatment; Standard Medical Treatment; Biological: 20% High Dose Albumin; A]. Patients in the conventional albumin Arm will receive Human Albumin 20% 1.5 g/kg body weight (Maximum 100g) on day 1 after the diagnosis, followed by 1 g/kg bodyweight (Maximum 100g)on day 3 along with standard medical therapy
Active Comparator: Reduced Dose Albumin+Standard Medical therapy; Human Albumin 20% 1.0 g/kg body weight (Maximum 100g) on day 1 after the diagnosis, followed by 0.5 g/kg bodyweight (Maximum 100g) on day 3 along with standard medical therapy.	Other: Standard Medical Treatment; Standard Medical Treatment; Biological: 20% Reduced Dose Albumin; B]. Patients in the low dose albumin Arm will receive Human Albumin 20% 1.0 g/kg body weight (Maximum 100g) on day 1 after the diagnosis, followed by 0.5 g/kg bodyweight (Maximum 100g) on day 3 along with standard medical therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients developing new AKI or having progression of AKI by day 4.	Day 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resolution of Spontaneous Bacterial Peritonitis by day 5	Resolution is defined as decrease in ascitic fluid PMN > 25% from baseline	Day 5
Change on Serum Ascites Albumin Gradient (SAAG) in both the groups.		Day 5
Change in cell count (PMN) in both groups.		Day 5
Changes in PRA levels from baseline to day 7		day 7
Changes in TNF-alpha levels from baseline to day 7		day 7
Changes in IL-6 levels from baseline to day 7		day 7
Changes in endotoxin levels from baseline to day 7		day 7
Changes in renal resistive index from baseline to day 7		day 7
Number of patients with development of complications in both groups		90 days
Number of Participants with changes in ProBNP from baseline to day 4 or if shortness of breath occurs		Day 4
Number of Participants with changes in vWF-Ag from baseline to day 4		Day 4
Number of patients expired in both the groups		Day 7
Number of patients expired in both the groups		Day 28
Number of patients expired in both the groups		Day 90
Duration of hospital stay		90 days

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Estimated): September 5, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: August 17, 2023
• First Submitted That Met QC Criteria: September 6, 2023
• First Posted (Actual): September 7, 2023

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 8, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Peritoneal Diseases; Liver Diseases; Intraabdominal Infections; Fibrosis; Liver Cirrhosis; Peritonitis
• Other Study ID Numbers: ILBS-Cirrhosis-59

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No