Bezlotoxumab Yielded Outcomes by Addressing Personalized Needs in Clostridioides Difficile Infection

NCT05304715 | Completed Phase 2 Results

• 2 other identifiers: BEYOND2021-005473-10
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 11

Brief Summary

Previous data have shown that integrated information from single nucleotide polymorphisms (SNPs) of the host DNA, interleukin 8 (IL-8) and the enrichment of the stool microbiome can indicate the patients with infection by Clostridioides difficile (CDI) who are at risk for unfavorable outcome. This integrated information is forming the BEYOND score. The aim of the BEYOND randomized clinical trial (RCT) is to investigate if adjunctive bezlotoxumab treatment to the current standard-of-care may decrease the likelihood of unfavorable outcome for patients who score positive by the BEYOND score.

Conditions

Clostridioides Difficile Infection; Stool Microbiome; Organ Dysfunction Syndrome; Clostridioides Difficile Infection Recurrence; Mortality

Keywords

Bezlotoxumab

Outcome Measures

Primary Outcomes (1)

• The Superiority of Bezlotoxumab Over Placebo to Reduce the Occurence of an Unfavorable Outcome by Day 40.

  Unfavorable outcome is defined as the presence of any of: organ dysfunction; CDI relapse; and/or death. Progression into organ dysfunction is defined as any increase of the baseline total SOFA score by at least 2 points. Need for colectomy or admission in the Intensive Care Unit counts also as organ dysfunction. The primary endpoint is tested on Day 40 from start of blind treatment

  40 days

Secondary Outcomes (5)

• The Superiority of Bezlotoxumab Over Placebo Regarding the Time to First Organ Dysfunction.

  1-40 days

• The Superiority of Bezlotoxumab Over Placebo to Reduce the Number of Participants Experiencing a CDI Relapse.

  1-40 days

• The Superiority of Bezlotoxumab Over Placebo to Reduce the Occurence of Death by Day 40.

  1-40 days

• The Superiority of Bezlotoxumab Over Placebo to Reduce the Overall Cost of Hospitalization

  1-40 days

• Validation of the BEYOND Score

  1-40 days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Patients will be treated with 250ml of normal saline 0.9% or 5% dextrose water as single intravenous infusion of one hour within 72 hours from the start of standard-of-care treatment. Standard-of-care treatment will be prescribed to all patients at the discretion of the attending physicians according to local guidelines or to their own decision.

Drug: Normal saline 0.9% or 5% dextrose water

Bezlotoxumab

ACTIVE COMPARATOR

Patients will be treated with bezlotoxumab at a dose of 10mg per kg of body weight (up to maximum of 1000mg) dissolved in 250ml of normal saline 0.9% or 5% dextrose water as single intravenous infusion of one hour within 72 hours from the start of standard-of-care treatment. Standard-of-care treatment will be prescribed to all patients at the discretion of the attending physicians according to local guidelines or to their own decision.

Drug: Bezlotoxumab

Interventions

Bezlotoxumab DRUG

Single intravenous infusion of bezlotoxumab

Also known as: Standard-of-care treatment according to local guidelines or to the decision of the attending physicians.

Bezlotoxumab

Normal saline 0.9% or 5% dextrose water DRUG

Single intravenous infusion - Placebo arm

Also known as: Standard-of-care treatment according to local guidelines or to the decision of the attending physicians

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age equal to or above18 years.
• Both genders.
• Written informed consent provided by the patient or by their legal representative in case of patients unable to consent.
• Diarrhea defined as at least 3 episodes of unformed stool in the past 24hours.
• Positive stool for C.difficile. This is defined as any stool sample positive for the presence of glutamate dehydrogenase (GDH) and for the presence of toxin A and/or B.
• Positive BEYOND score i.e. meeting any of the following:
• Gene score for susceptibility to CDI more than 53. The score is provided by the following equation:
• (Carriage of C allele of rs12148744 x 27) - (carriage of C allele of rs714024 x 27) - (carriage of C allele of rs721059 x 29) + (carriage of T allele of rs4311028 x 33) - (carriage of A allele of rs62183547 x 25) + (carriage of C allele of rs1128266 x 12) - (carriage of T allele of rs4279595 x 17) + (carriage of G allele of rs175006 x 11) + (carriage of T allele of rs3859214 x 17) + (carriage of G allele of rs7222870 x 15) - (carriage of G allele of rs5086600 x 9) + (carriage of T allele of rs7240534 x 12) + (carriage of G allele of rs20911172 x 11) - (carriage of C allele of rs17680671 x 17) OR
• Score provided by the following equation more than 9:
• \[Hemoglobin \<9.5 g/dl x 10\] + \[serum urea \>64.5 mg/dl x 14\] + \[serum interleukin-8 \>227 pg/ml x 19\] - \[carriage of G allele of rs2091172 x 17\] OR More than 3log10 of gammaproteobacteria or Enterobacteriaceae or Enterobacteriales in the stool

You may not qualify if:

• Age below 18 years
• Denial for written informed consent
• Known allergy to bezlotoxumab

Sponsors & Collaborators

• Hellenic Institute for the Study of Sepsis: lead

Study Sites (11)

2nd Department of Internal Medicine, University General Hospital of Alexandroupolis

Alexandroupoli, 68100, Greece

Location

1st Department of Internal Medicine, THRIASIO General Hospital of Eleusis

Athens, 10918, Greece

Location

2nd Department of Internal Medicine, Thriasio General Hospital

Athens, 10918, Greece

Location

1st University Department of Internal Medicine, LAIKO General Hospital of Athens,

Athens, 11527, Greece

Location

1st University Department of Propaedeutic Surgery, IPPOKRATEION General Hospital

Athens, 11527, Greece

Location

4th Department of Internal Medicine, Attikon University Hospital

Athens, 12462, Greece

Location

1st Department of Internal Medicine, General University Hospital of Ioannina

Ioannina, 45500, Greece

Location

Department of Internal Medicine, Larissa University Hospital

Larissa, 41334, Greece

Location

Department of Internal Medicine, University General Hospital of Patras PANAGIA I VOITHIA

Pátrai, 26504, Greece

Location

2nd Department of Internal Medicine, Tzanneion General Hospital

Piraeus, 18536, Greece

Location

1st Department of Internal Medicine, AHEPA University General Hospital of Thessaloniki

Thessaloniki, 54621, Greece

Location

Related Publications (1)

• Psarrakis C, Tziolos NR, Matzarakis V, Kumar V, Stylianakis E, Sidiropoulou C, Tasouli E, Iliopoulou K, Samarkos M, Metallidis S, Georgiadou S, Akinosoglou K, Bolanou A, Hatziagelaki E, Kostaki A, Panagopoulos P, Toutouzas K, Milionis H, Adamis G, Poulakou G, Lada M, Skoutelis A, Alexiou Z, Symbardi S, Chrysos G, Netea MG, Giamarellos-Bourboulis EJ. A randomized controlled trial of precision bezlotoxumab treatment for Clostridioides difficile infection. Cell Rep Med. 2026 Jan 20;7(1):102533. doi: 10.1016/j.xcrm.2025.102533. Epub 2026 Jan 2.

  PMID: 41483804 DERIVED

MeSH Terms

Conditions

Clostridium Infections

Interventions

bezlotoxumab; Saline Solution

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

Five main limitations of the BEYOND project should be acknowledged: 1. The small number of participants in both stages of the study. 2. The limited power of GWAS to perform direct 3. The conduct of the study only in Greek patients 4. The lack of Clostridioides difficile ribotyping; and 5. The need to build a point-of-care diagnostic panel in the future, which will integrate the seven components of the score, taking into consideration the implementation in two steps.

Results Point of Contact

• Title: Evangelos J. Giamarellos-Bourboulis
• Organization: Hellenic Institute for the Study of Sepsis and 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece

egiamarel@med.uoa.gr

+302107480662

Study Officials

• Evangelos J Giamarellos-Bourboulis, MD, PhD

  Hellenic Sepsis Study Group

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a prospective, 1:1 randomized, double-blind, placebo-controlled trial

Study Record Dates

• First Submitted: March 12, 2022
• First Posted: March 31, 2022
• Study Start: April 13, 2022
• Primary Completion: June 4, 2023
• Study Completion: June 4, 2023
• Last Updated: March 4, 2026
• Results First Posted: March 4, 2026

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

GR (11)