VANCALLO - Prevention of C. difficile infections by oral vancomycin in patients treated for allogeneic hematopoietic stem cell transplantation, a randomized double-blind placebo-controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

27 Oct 2022 → ongoing

Decision date (initial)

2024-06-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

[DGOS - Ministry of Higher Education and Research] : PHRC Inter-régional Ile de France 2020

External identifiers

EU CT number

2024-513490-45-00

EudraCT number

2021-003835-28

ClinicalTrials.gov

NCT05256693

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Evaluate the effectiveness of primary prophylaxis with oral vancomycin on the prevention of Clostridium difficile infections in patients hospitalized for allogeneic HCT transplantation.

Secondary objectives 14

1. In patients receiving an allogeneic HSC transplant, evaluate the impact of primary prophylaxis with oral vancomycin on: - prevention of Clostridium difficile infections occurring after stopping primary prophylaxis (until week 12)
2. - the prevention of Clostridium difficile infections in patients hospitalized for HSC allogeneic transplantation (up to W5) in terms of cumulative incidence up to W5
3. - prevention of Clostridium difficile infections in hospitalized patients with a diagnosis made by PCR detection of the toxigenic strain
4. - the severity of CD infections occurring under treatment
5. - risk factors for the occurrence of CD infection: type of packaging, antibiotics received, presence of toxigenic strain on D0 of treatment and composition of the microbiota (as part of the ancillary study),
6. - the profile of bacterial infections occurring during treatment with vancomycin or placebo
7. - the impact of the treatment on the intestinal microbiota (as part of the ancillary study)
8. - the emergence of vancomycin-resistant enterococcus (VRE)
9. - the occurrence of nosocomial clusters of CD infection up to W12
10. - the occurrence of acute or chronic GVHD at M12
11. - relapse of hematological disease
12. - mortality linked to the transplant procedure (TRM) at 1 month
13. - overall survival at M12
14. - tolerance

Conditions and MedDRA coding

Patients hospitalized for allogeneic hematopoietic stem cell transplantation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. - Age ≥15 years
2. - Patient hospitalized for less than 72 hours to receive an allograft of HSC, whatever the indication and packaging,
3. - for men and women of childbearing age: use of effective contraception (failure rate less than 1% per year) throughout the Research and up to 1 month after the end of treatment (see point 6.1 Inclusion criteria)
4. - Have given consent for participation in the study.
5. - Beneficiary of health insurance

Exclusion criteria 7

1. - Documented allergy or adverse reactions to vancomycin
2. - Pregnancy and breast feeding
3. - Clostridium difficile infection within 30 days preceding inclusion or on the day of inclusion
4. - History of total colectomy and/or chronic inflammatory bowel disease
5. - Progressive diarrhea at inclusion regardless of the etiology
6. - Digestive decontamination protocol during the transplant procedure
7. - Participation in another medicinal intervention research involving humans or being in the exclusion period following previous research involving humans, if applicable

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Clostridium difficile infection, occurring between inclusion and discharge from hospitalization or the end of treatment with vancomycin or placebo (i.e. after 5 weeks of treatment (W5) if the patient is still hospitalized), defined by diarrhea (> 3 unformed stools/day) with detection of CD (GDH) and free toxin in the stools by enzyme immunoassay without argument for another etiology of diarrhea or existence of pseudomembranous colitis at endoscopy, at colectomy or at autopsy.

Secondary endpoints 14

1. - Clostridium difficile infection, occurring between inclusion and W12, defined by diarrhea (> 3 unformed stools/day) with detection of CD and free toxin in the stools by immunoenzymatic method without argument for another etiology in diarrhea or presence of pseudomembranous colitis at endoscopy, colectomy or autopsy.
2. - Time between inclusion and Clostridium difficile infection as defined in the primary endpoint, in a maximum window up to W5
3. - Clostridium difficile infection, occurring between inclusion and discharge from hospitalization or the end of treatment with vancomycin or placebo (i.e. after 5 weeks of treatment (W5) if the patient is still hospitalized), defined by diarrhea (> 3 unformed stools/day) with detection of toxigenic CD by PCR without argument for another etiology of diarrhea or existence of pseudomembranous colitis at endoscopy, colectomy or autopsy.
4. - Risk factors for CD infection: type of packaging, antibiotics received, presence of toxigenic strain on D0 of treatment (D0V), composition of the microbiota
5. - Severity factors of CD infections occurring during the procedure
6. - Microbiologically documented bacterial infection(s) (regardless of the infectious source) occurring during treatment with 125 mg of vancomycin (i.e. up to 5 weeks maximum)
7. - Acquisition of rectal carriage of vancomycin-resistant Enterococcus (VRE) between randomization and the end of treatment (discharge from hospitalization or W5 maximum) measured by rectal swab
8. - Study of the intestinal microbiota at inclusion, during treatment (14 days after initiation of treatment, i.e. W2), at the end of treatment (W5 or before discharge from hospitalization) and remotely (W12) as part of the ancillary study
9. - Occurrence of nosocomial clusters of CD infection at W12 defined as the occurrence of at least 2 cases of CDI over a period of time defined according to the incidence usually observed in the investigating center
10. - Occurrence of acute or chronic GVHD grade 2-4 at M12
11. - Time between inclusion and relapse of the hematological disease, or the date of last news (maximum M12)
12. - Mortality rate linked to the transplant procedure (TRM) at W5
13. - Delay between inclusion and death, or the date of last news (maximum M12)
14. - Proportion of adverse effects during protocol monitoring

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Inès BOUSSEN

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Inès BOUSSEN

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Application history

1 submissions — initial application plus substantial / non-substantial modifications