Prevention of C.Difficile Infections With Oral Vancomycine in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant

Phase 3

Not yet recruiting

• Conditions: Stem Cell Transplant Complications; Clostridium Difficile Infections
• Interventions: Drug: Placebo; Drug: Vancomycin

• Registration Number: NCT05256693
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Clostridium difficile (CD) infection are an important cause of morbi-mortality in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). The VANCALLO trial aims at evaluating oral vancomycine reducing the risk of CD infection relying on a placebo controlled 1:1 randomized design, including one interim analysis.

Detailed Description

Not available

Study Timeline

• Status Verified: 2021-11
• Study First Submitted: 2022-01-28
• Study First Submitted QC: 2022-02-17
• Last Update Submitted: 2022-02-17
• Study First Posted: 2022-02-25
• Last Update Posted: 2022-02-25
• Study Start: 2022-03
• Primary Completion: 2024-06
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 336

Inclusion Criteria

• Age ≥15 ans
• Hospitalization since less than 72 hours, for an allogeneic stem cell transplant, whichever the indication and conditioning
• For men and women of reproductive age: use of contraceptives
• Informed consent
• Healthcare insurance

Exclusion Criteria

• Know allergy or history of adverse events with vancomycine
• Pregnancy
• Clostridium difficile infection within 30 days prior to inclusion or at inclusion
• History of total colectomy and/or inflammatory bowel disease
• Progressive diarrhea at inclusion, whichever the etiology
• Digestive decontamination protocol for the stem cell transplant procedure
• Participation to another drug clinical trial or being in the exclusion period from a prior clinical trial participation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Vancomycine placebo, twice a day, from inclusion (at the time of hospitalization for allogeneic stem cell transplant) until hospital discharge or 5 weeks in hospital at most.
Vancomycine	Vancomycin	Oral vancomycine 125 mg twice a day, from inclusion (at the time of hospitalization for allogeneic stem cell transplant) until hospital discharge or 5 weeks in hospital at most.

Primary Outcome Measures

Name	Time	Method
Proportion of patients with Clostridium difficile infection	5 weeks	Clostridium difficile infection defined as a diarrhea (\> 3 loose stools/day) with positive Clostridium difficile testing and free-toxin in stools by enzyme-linked immunosorbent assay (ELISA), without other obvious etiology for diarrhea nor pseudo-membraneous colitis (endoscopy, colectomy, autopsy).

Secondary Outcome Measures

Name	Time	Method
Factors associated with the proportion of patients with Clostridium difficile infection	5 weeks	Candidate factors associated with Clostridium difficile infection: antibiotics, toxinogenic strain at baseline, microbiota composition
Proportion of patients with vancomycin-resistant enterococcus carriage	5 weeks	Carriage defined as occurrence of vancomycin-resistant enterococcus carriage on rectal swab
Gut microbiome profile	12 weeks	Evolution of gut microbiome profile during the study
Proportion of patients with Graft-versus-Host disease	12 months	Graft-versus-Host disease, acute or chronic, grade 2 to 4
Treatment-related mortality	5 weeks	Proportion of death related to allogeneic stem cell transplant procedures
Cumulative incidence of Clostridium difficile infection	5 weeks	Time between inclusion and Clostridium difficile infection, occurring before hospital discharge or the end of study treatment (that is 5 weeks from inclusion if the patient is still hospitalized), defined as a diarrhea (\> 3 loose stools/day) with positive Clostridium difficile testing and free-toxin in stools by enzyme-linked immunosorbent assay (ELISA), without other obvious etiology for diarrhea nor pseudo-membraneous colitis (endoscopy, colectomy, autopsy).
Cumulative incidence of relapse	12 months	Time between inclusion and hemopathy relapse or last follow-up, up to a maximum of 12 months
Proportion of patients with severe Clostridium difficile infection	5 weeks	Severe Clostridium difficile infection defined as at least one of the following: fulminans colitis, toxic megacolon, dehydration, neutrophils blood count\>20000/mm3, general deterioration
Overall survival	12 months	Time between inclusion and death or last follow-up, up to a maximum of 12 months
Proportion of patients with Clostridium difficile infection by PCR testing	5 weeks	Clostridium difficile infection defined as a diarrhea (\> 3 loose stools/day) with positive toxinogenic Clostridium difficile PCR (polymerase chain reaction) testing, without other obvious etiology for diarrhea nor pseudo-membraneous colitis (endoscopy, colectomy, autopsy).
Nosocomial Clostridium difficile infection clusters	12 weeks	Defined as at least 2 cases of Clostridium difficile infection in the department within 12 weeks
Proportion of patients with Clostridium difficile infection	12 weeks	Clostridium difficile infection defined as a diarrhea (\> 3 loose stools/day) with positive Clostridium difficile testing and free-toxin in stools by enzyme-linked immunosorbent assay (ELISA), without other obvious etiology for diarrhea nor pseudo-membraneous colitis (endoscopy, colectomy, autopsy).
Proportion of patients with bacterial infection	5 weeks	Bacterial infection defined as occurrence of a bacterial infection (any site)