Optimization of Antibiotic Treatment in Hematopoietic Stem Cell Receptors

Graft Versus Host Disease Clinical Trial

— Optimbioma  

Official title:

Optimization of Antibiotic Treatment in Hematopoietic Stem Cell Receptors: Impact on Intestinal Microbiota and in Clinical Outcomes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03727113
• Other study ID #: Optimbioma
• Status: Completed
• Start date: January 16, 2018
• Est. completion date: June 30, 2021

Study information

• Verified date: February 2023
• Source: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 211
• Est. completion date: June 30, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease
• Hematopoietic Stem Cell Transplantation

Intervention

Procedure:
• Optimization cohort
Recipients of an allogeneic hemopoietic stem cell transplant in Centers using an optimization/antibiotic strategy.
• Control cohort
Recipients of an allogeneic hemopoietic stem cell transplant in Centers using a classical strategy of administration of antibiotics.

Locations

Country	Name	City	State
Spain	Gregorio Marañón University Hospital	Madrid
Spain	Salamanca University Hospital	Salamanca
Spain	Marqués de Valdecilla University Hospital	Santander
Spain	Virgen del Rocío University Hospital, Seville.	Sevilla	Seville
Spain	University Clinical Hospital of Valencia	Valencia

Sponsors (3)

Lead Sponsor	Collaborator
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla	Grupo Espanol de trasplantes hematopoyeticos y terapia celular, Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

References & Publications (2)

Aguilar-Guisado M, Espigado I, Martin-Pena A, Gudiol C, Royo-Cebrecos C, Falantes J, Vazquez-Lopez L, Montero MI, Rosso-Fernandez C, de la Luz Martino M, Parody R, Gonzalez-Campos J, Garzon-Lopez S, Calderon-Cabrera C, Barba P, Rodriguez N, Rovira M, Montero-Mateos E, Carratala J, Perez-Simon JA, Cisneros JM. Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol. 2017 Dec;4(12):e573-e583. doi: 10.1016/S2352-3026(17)30211-9. Epub 2017 Nov 15. — View Citation

Averbuch D, Orasch C, Cordonnier C, Livermore DM, Mikulska M, Viscoli C, Gyssens IC, Kern WV, Klyasova G, Marchetti O, Engelhard D, Akova M; ECIL4, a joint venture of EBMT, EORTC, ICHS, ESGICH/ESCMID and ELN. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica. 2013 Dec;98(12):1826-35. doi: 10.3324/haematol.2013.091025. Erratum In: Haematologica. 2014 Feb;99(2):400. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Impact on microbiota	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).	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.
Secondary	Incidence of Acute graft versus host disease	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.	From the day of transplant (Day 0) to Day +100 posttransplant
Secondary	Transplant related mortality	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.	From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant
Secondary	Mortality caused by infection	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.	From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant
Secondary	Incidence of severe infections	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.	From the day of transplant (Day 0) to Day +30 posttransplant
Secondary	Overall survival	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.	From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant
Secondary	Disease free survival	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.	From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant