Optimization of Antibiotic Treatment in Hematopoietic Stem Cell Receptors

Completed

• Conditions: Hematopoietic Stem Cell Transplantation; Graft Versus Host Disease
• Interventions: Procedure: Control cohort; Procedure: Optimization cohort

• Registration Number: NCT03727113
• Lead Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Brief Summary

There are data suggesting that the reduction of the diversity of intestinal microbiota caused by the used treatments in the setting of allogeneic hemopoietic stem cell transplant (ASCT), and specially antibiotics, may be related to increased incidence of graft versus host disease (GVHD) and worst clinical outcomes. Present "European Conference on Infections in Leukaemia" guidelines exhort to antibiotic treatment optimization in hematological patients, without excluding ASCT receptors. This study aims to demonstrate that in ASCT receptors a predefined protocol of optimization of the antibacterial treatment will preserve the intestinal microbiota diversity which will correlate with decrease incidence of acute GVHD. And that this procedure is safe because it will not worsen the incidence of infections, transplant related mortality, infectious mortality or global survival.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-01-16
• Study First Submitted: 2018-10-16
• Study First Submitted QC: 2018-10-30
• Study First Posted: 2018-11-01
• Primary Completion: 2021-06-30
• Study Completion: 2021-06-30
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-16
• Last Update Posted: 2023-02-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 211

Inclusion Criteria

• Patients admitted to receive their first allogeneic hematopoietic transplant as a treatment of any disease.
• Conformity of the patient to participate by signing the informed consent.
• Patients who have received a previous autologous transplant are not excluded.

Exclusion Criteria

• Non-compliance of the patient to sign the informed consent.
• Patients who have already started the conditioning (or thereafter) will not be included.
• Allograft recipients who have previously received the transplant will not be included. Second allogeneic transplants are excluded.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Control cohort	Control cohort	Patients receiving an allogeneic hemopoietic stem cell transplant in Centers using a classical strategy of administration of antibiotics.
Optimization cohort	Optimization cohort	Patients receiving an allogeneic hemopoietic stem cell transplant in Centers using an optimization/antibiotic strategy.

Primary Outcome Measures

Name	Time	Method
Impact on microbiota	From the Previous Day of starting conditioning treatment until the last documented day of antibiotherapy or hospital discharge, whichever came first, assessed up to one month post-transplant.	Comparison of biological alpha and beta diversity of the intestinal microbiota of both study groups (classical and optimized antibiotherapy). Calculation of alpha diversity (OTUs richness and Shannon diversity indexes observed, Faith's Phylogenetic Diversity and Evenness) and beta diversity (Jaccard distance, Bray-Curtis distance, Unweighted UniFra distance, used for comparing biological communities) indexes by QIIME 2 (microbiome bioinformatics platform).

Secondary Outcome Measures

Name	Time	Method
Transplant related mortality	From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant	Comparison of transplant related mortality between both study groups (classical and optimized antibiotherapy). Cumulative Incidence curve estimation. Test for the comparison of groups: Gray Test.
Incidence of severe infections	From the day of transplant (Day 0) to Day +30 posttransplant	Comparison of the incidence of severe infections between both study groups (classical and optimized antibiotherapy). Cumulative Incidence curve estimation. Test for the comparison of groups: Gray Test.
Overall survival	From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant	Comparison of overall survival between both study groups (classical and optimized antibiotherapy) Kaplan-Meier curve estimation. Test for the comparison of groups: Log-Rank Test.
Incidence of Acute graft versus host disease	From the day of transplant (Day 0) to Day +100 posttransplant	Comparison of the incidence of any degree, degree-II and degree-III/IV of acute graft versus host disease between the groups of patients with high and low diversity in their microbiota. Cumulative Incidence curve estimation.; Test for the comparison of groups: Gray Test.
Disease free survival	From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant	Comparison of the diseae free survival between both study groups (classical and optimized antibiotherapy Kaplan-Meier curve estimation. Test for the comparison of groups: Log-Rank Test.
Mortality caused by infection	From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant	Comparison of infection related mortality between both study groups (classical and optimized antibiotherapy. Cumulative Incidence curve estimation. Test for the comparison of groups: Gray Test.

Trial Locations

Locations (5)

Virgen del Rocío University Hospital, Seville.; 🇪🇸 Sevilla, Seville, Spain

Salamanca University Hospital; 🇪🇸 Salamanca, Spain

University Clinical Hospital of Valencia; 🇪🇸 Valencia, Spain

Marqués de Valdecilla University Hospital; 🇪🇸 Santander, Spain

Gregorio Marañón University Hospital; 🇪🇸 Madrid, Spain