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

Study Overview
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Brief Summary
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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.

Official Title
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Prevention of C.Difficile Infections With Oral Vancomycine in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant: a Double-blind Placebo-controlled Randomized Clinical Trial

Conditions
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Clostridium Difficile Infections, Stem Cell Transplant Complications

Intervention / Treatment
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* Drug: Vancomycin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vancomycine<br>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. | Drug: Vancomycin<br>* Oral vancomycin (powder) 125mg twice a day<br>|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* Vancomycine placebo (powder) twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with Clostridium difficile infection | 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). | 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with Clostridium difficile infection | 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). | 12 weeks | 
| Cumulative incidence of Clostridium difficile infection | 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). | 5 weeks | 
| Proportion of patients with Clostridium difficile infection by PCR testing | 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). | 5 weeks | 
| Factors associated with the proportion of patients with Clostridium difficile infection | Candidate factors associated with Clostridium difficile infection: antibiotics, toxinogenic strain at baseline, microbiota composition | 5 weeks | 
| Proportion of patients with severe Clostridium difficile infection | Severe Clostridium difficile infection defined as at least one of the following: fulminans colitis, toxic megacolon, dehydration, neutrophils blood count>20000/mm3, general deterioration | 5 weeks | 
| Proportion of patients with bacterial infection | Bacterial infection defined as occurrence of a bacterial infection (any site) | 5 weeks | 
| Proportion of patients with vancomycin-resistant enterococcus carriage | Carriage defined as occurrence of vancomycin-resistant enterococcus carriage on rectal swab | 5 weeks | 
| Gut microbiome profile | Evolution of gut microbiome profile during the study | 12 weeks | 
| Nosocomial Clostridium difficile infection clusters | Defined as at least 2 cases of Clostridium difficile infection in the department within 12 weeks | 12 weeks | 
| Proportion of patients with Graft-versus-Host disease | Graft-versus-Host disease, acute or chronic, grade 2 to 4 | 12 months | 
| Cumulative incidence of relapse | Time between inclusion and hemopathy relapse or last follow-up, up to a maximum of 12 months | 12 months | 
| Treatment-related mortality | Proportion of death related to allogeneic stem cell transplant procedures | 5 weeks | 
| Overall survival | Time between inclusion and death or last follow-up, up to a maximum of 12 months | 12 months |