Optimbioma: Optimization of Antibiotic Treatment in Hematopoietic Stem Cell Receptors
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Control cohort Patients receiving an allogeneic hemopoietic stem cell transplant in Centers using a classical strategy of administration of antibiotics. |
Procedure: Control cohort
Recipients of an allogeneic hemopoietic stem cell transplant in Centers using a classical strategy of administration of antibiotics.
|
| Optimization cohort Patients receiving an allogeneic hemopoietic stem cell transplant in Centers using an optimization/antibiotic strategy. |
Procedure: Optimization cohort
Recipients of an allogeneic hemopoietic stem cell transplant in Centers using an optimization/antibiotic strategy.
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients admitted to receive their first allogeneic hematopoietic transplant as a treatment of any disease.
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Conformity of the patient to participate by signing the informed consent.
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Patients who have received a previous autologous transplant are not excluded.
Exclusion Criteria:
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Non-compliance of the patient to sign the informed consent.
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Patients who have already started the conditioning (or thereafter) will not be included.
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Allograft recipients who have previously received the transplant will not be included. Second allogeneic transplants are excluded.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Virgen del Rocío University Hospital, Seville. | Sevilla | Seville | Spain | 41013 |
| 2 | Gregorio Marañón University Hospital | Madrid | Spain | 28007 | |
| 3 | Salamanca University Hospital | Salamanca | Spain | 37007 | |
| 4 | Marqués de Valdecilla University Hospital | Santander | Spain | 39008 | |
| 5 | University Clinical Hospital of Valencia | Valencia | Spain | 46010 |
Sponsors and Collaborators
- Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
- Grupo Espanol de trasplantes hematopoyeticos y terapia celular
- Instituto de Salud Carlos III
Investigators
- Principal Investigator: Ildefonso Espigado, PhD, MD, Hematology Service, Hematopoietic Transplant Program, Seville Biomedicine Institute (IBIS) - Virgen del Rocío University Hospital, Seville.
Study Documents (Full-Text)
None provided.More Information
Publications
- Aguilar-Guisado M, Espigado I, Martín-Peña A, Gudiol C, Royo-Cebrecos C, Falantes J, Vázquez-López L, Montero MI, Rosso-Fernández C, de la Luz Martino M, Parody R, González-Campos J, Garzón-López S, Calderón-Cabrera C, Barba P, Rodríguez N, Rovira M, Montero-Mateos E, Carratalá J, Pérez-Simón 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.
- 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.
- Optimbioma