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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Stem Cell Transplant Complications; Clostridium Difficile Infections
• Intervention / Treatment: Drug: Vancomycin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 336
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Inès Boussen, MD; Phone Number: +33 1 42 49 90 66; Email: ines.boussen@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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: Vancomycine; 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; Oral vancomycin (powder) 125mg twice a day
Placebo Comparator: 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.	Drug: Placebo; Vancomycine placebo (powder) twice a day

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: GIRCI Ile de France

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2022
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): July 1, 2025

Study Registration Dates

• First Submitted: January 28, 2022
• First Submitted That Met QC Criteria: February 17, 2022
• First Posted (Actual): February 25, 2022

Study Record Updates

• Last Update Posted (Actual): February 25, 2022
• Last Update Submitted That Met QC Criteria: February 17, 2022
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Clostridium Infections; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin
• Other Study ID Numbers: APHP210089

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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