Administration of Probiotics in Cirrhotic Patients Listed for Liver Transplantation

An Attempt to Optimize the Results of Liver Transplantation With Administration of Probiotics.

The aim of this study was to evaluate the impact of the administration of probiotics on outcomes of patients qualified for liver transplantation, both in the pre-transplant period and in the early postoperative period.

Study Overview

• Status: Completed
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Dietary supplement: Probiotic; Dietary supplement: Placebo

Detailed Description

Gut microflora plays an important role in the pathogenesis of complications of liver cirrhosis, mainly due to microbial translocation. According to several studies, administration of probiotics in patients with cirrhosis has positive effect on minimal hepatic encephalopathy. The aim of this study was to evaluate the impact of probiotics administration on outcomes of patients qualified for liver transplantation, both in the pre-transplant period and in the early postoperative period. This study will be performed on 200 patients randomized into the probiotic and placebo groups. Daily administration of either probiotics or placebo will be continued from the date of inclusion in the study until the date of liver transplantation. A quantitative and qualitative analyses of faecal microflora will be performed in each patient before and after 10 week period (or shorter, depending on the time on the waiting list) of administration of either probiotic or placebo. Microbiological analyses of air samples from patients' home environment will be performed in each case. Both groups of patients will be compared with respect to primary and secondary outcome measures.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Mazowieckie
    • Warsaw, Mazowieckie, Poland, 02-097
      • Department of General, Transplant and Liver Surgery, Medical University of Warsaw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Liver cirrhosis
• Active status on the waiting list for liver transplantation
• Confirmed etiology of liver disease

Exclusion Criteria:

• Malignancy
• Human Immunodeficiency Virus infection
• Immunosuppressive treatment prior to liver transplantation
• Cystic fibrosis
• Creatinine clearance rate < 50 mL/min

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic; Capsules with 3x10^9 colony forming units (Lactococcus lactis PB 411 - 50%; Lactobacillus casei PB 121 - 25%; Lactobacillus acidophilus PB 111 - 12,5%; Bifidobacterium bifidum PB 211 - 12,5%). 1 capsule a day from inclusion until liver transplantation	Dietary supplement: Probiotic; Capsules with 3x10^9 colony forming units of: Lactococcus lactis PB 411 (50%), Lactobacillus casei PB 121 (25%), Lactobacillus acidophilus PB 111 (12,5%), Bifidobacterium bifidum PB 211 (12,5)
Placebo Comparator: Placebo; Placebo, 1 capsule a day from inclusion until the date of liver transplantation	Dietary supplement: Placebo; Placebo, 1 capsule a day from inclusion until the date of liver transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
All-cause postoperative mortality	90 days after the date of liver transplantation
Postoperative infection	30 days from the date of liver transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality on the waiting list		From the date of inclusion until the date of liver transplantation
Infections in the pre-transplantation period		From the date of inclusion until the date of transplantation
Primary non-function after liver transplantation		14 days after the date of liver transplantation
Changes in model for end-stage liver disease score		From the date of inclusion until the date of transplantation
Changes in Child-Turcotte-Pugh class		From the date of inclusion until the date of transplantation
Number of hospital admissions due to infections in the pre-transplantation period		From the date of inclusion until the date of transplantation
Number of hospital admission due to complications of liver cirrhosis in the pre-transplantation period		From the date of inclusion until the date of transplantation
Serum activity of transaminases on the first 5 postoperative days		5 days after the date of liver transplantation
Serum bilirubin concentration in the first 5 postoperative days		5 days after the date of liver transplantation
International normalized ratio values during the first 5 postoperative days		5 days after the date of liver transplantation
Change in model for end-stage liver disease score in the pre-transplantation period	To be assessed if the period between inclusion in the study and liver transplantation would not be shorter than 10 weeks	10 weeks
Change in Chil-Turcotte-Pugh class in the pre-transplantation period	To be assessed if the period between inclusion in the study and liver transplantation would not be shorter than 10 weeks	10 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in faecal microflora	Differences in the number of colony forming units in 1 g of stool for particular bacterial and fungal species after 10 weeks of probiotic/placebo administration	10 weeks

Collaborators and Investigators

• Sponsor: Medical University of Warsaw
• Collaborators: Ministry of Science and Higher Education, Poland
• Investigators: Principal Investigator: Michał Grąt, M.D., Medical University of Warsaw, Department of General, Transplant and Liver Surgery; Study Chair: Marek Krawczyk, Professor, Medical University of Warsaw, Department of General, Transplant and Liver Surgery

Publications and helpful links

General Publications

• Cooper TE, Scholes-Robertson N, Craig JC, Hawley CM, Howell M, Johnson DW, Teixeira-Pinto A, Jaure A, Wong G. Synbiotics, prebiotics and probiotics for solid organ transplant recipients. Cochrane Database Syst Rev. 2022 Sep 20;9(9):CD014804. doi: 10.1002/14651858.CD014804.pub2.
• Grąt M, Grąt K, Krawczyk M, Lewandowski Z, Krasnodębski M, Masior Ł, Patkowski W, Zieniewicz K. Post-hoc analysis of a randomized controlled trial on the impact of pre-transplant use of probiotics on outcomes after liver transplantation. Sci Rep. 2020 Nov 17;10(1):19944. doi: 10.1038/s41598-020-76994-3.
• Grat M, Wronka KM, Lewandowski Z, Grat K, Krasnodebski M, Stypulkowski J, Holowko W, Masior L, Kosinska I, Wasilewicz M, Raszeja-Wyszomirska J, Rejowski S, Bik E, Patkowski W, Krawczyk M. Effects of continuous use of probiotics before liver transplantation: A randomized, double-blind, placebo-controlled trial. Clin Nutr. 2017 Dec;36(6):1530-1539. doi: 10.1016/j.clnu.2017.04.021. Epub 2017 May 4.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: November 23, 2012
• First Submitted That Met QC Criteria: November 27, 2012
• First Posted (Estimate): November 28, 2012

Study Record Updates

• Last Update Posted (Estimate): July 29, 2016
• Last Update Submitted That Met QC Criteria: July 28, 2016
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Liver transplantation; Probiotics; Mortality; Infections; Liver cirrhosis; Liver function
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: 1WB/3DG1