Probiotic Efficacy in VRE Eradication (PROVE)

The Effect of a Lactobacillus Probiotic Strain on Eradication of Vancomycin Resistant Enterococcus Faecium (VRE) in Non-symptomatic VRE-carriers - a Multicenter, Randomized, Placebo-controlled, Parallel-group Study With 4 Weeks Intervention

This study will evaluate the efficacy of a probiotic lactobacillus strain in eradicating VRE in non-symptomatic carriers after 4 weeks of treatment. It will also evaluate the long-term efficacy after 8,16 and 24 weeks.

Study Overview

• Status: Completed
• Conditions: VRE Colonization
• Intervention / Treatment: Other: placebo; Dietary supplement: lactobacillus probiotic strain

Detailed Description

With the increased number of Vancomycin-Resistant Enterococcus faecium (VRE) infected/colonized people it is evident that new treatment options are needed to reduce the number of VRE cases. One such option could be to use probiotics. We hypothesize that treatment with a probiotic lactobacillus strain can reduce the number of VRE carriers significantly. The aim is to investigate if this strain can eradicate VRE in non-symptomatic VRE-carriers measured as the number of subjects without VRE colonization at week 4.

This is a multi-center, randomized, double-blind, placebo-controlled parallel-group trial in non-symptomatic VRE-carriers.

The Trial consists of a 4 weeks intervention period followed by a 20-week follow-up period.

After patients have been confirmed as carriers of VRE, the subjects are randomized to 4 weeks' treatment with a lactobacillus probiotic strain (60 billion CFU per day) or to placebo. Subjects' VRE carrier-state is assessed at weeks 4, 8, 16 and 24, by an in-house PCR analysis. Stool samples are collected before intervention (baseline) and at week 4, 8, 16 and week 24.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen
    • Hvidovre, Copenhagen, Denmark, 2650
      • Hvidovre Hospital, Copenhagen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Subjects with VRE colonization (positive faecal swab)
• Subjects over 18 years of age
• Provided voluntary written informed consent

Exclusion Criteria:

• Symptomatic VRE infection
• Serious immunodeficiency
• Pancreatitis
• Planned or recent intraabdominal operation within a time window of14 days)
• Parenteral nutrition
• Antibiotic treatment for VRE one month prior to inclusion
• Terminal disease with expected survival time < 3 month
• Probiotic consumption within two weeks prior enrollment
• Pregnant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Other: placebo; placebo comparator
Experimental: lactobacillus probiotic strain; 60 billion CFU/day	Dietary supplement: lactobacillus probiotic strain; Approved Dietary supplement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with cleared VRE colonization at week 4	Fecal sample diagnosed by pcr and detection of the vanA gene	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clearance of VRE colonization at week 8, 16 and 24 respectively	Fecal sample diagnosed by pcr and detection of the vanA gene	8, 16 and 24 weeks
Number of VRE infections (isolation from non-intestinal foci)		24 weeks
Changes in fecal microbiota composition		24 weeks
Colonization with probiotic lactobacillus strain		24 weeks

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital
• Collaborators: Chr Hansen

Publications and helpful links

General Publications

• Rubin IMC, Mollerup S, Broholm C, Knudsen SB, Baker A, Helms M, Holm MKA, Kallemose T, Westh H, Dahl Knudsen J, Pinholt M, Petersen AM. No Effect of Lactobacillus rhamnosus GG on Eradication of Colonization by Vancomycin-Resistant Enterococcus faecium or Microbiome Diversity in Hospitalized Adult Patients. Microbiol Spectr. 2022 Jun 29;10(3):e0234821. doi: 10.1128/spectrum.02348-21. Epub 2022 Apr 27.

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2018
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): November 1, 2021

Study Registration Dates

• First Submitted: May 24, 2018
• First Submitted That Met QC Criteria: June 6, 2018
• First Posted (Actual): June 18, 2018

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: September 29, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: H-18011991

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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