Clinical trial NCT03727113: Optimization of Antibiotic Treatment in Hematopoietic Stem Cell Receptors
Official title: Optimization of Antibiotic Treatment in Hematopoietic Stem Cell Receptors: Impact on Intestinal Microbiota and in Clinical Outcomes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hematopoietic Stem Cell Transplantation
Graft Versus Host Disease
Keywords: microbiota
microbiome
graft versus host disease
infection
antibiotics
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
Collaborators: name: Grupo Espanol de trasplantes hematopoyeticos y terapia celular
name: Instituto de Salud Carlos III
First posted: 2018-11-01
Enrollment: 211
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients (\> 18 years old) who are going to receive their first hematopoietic allogeneic transplant of any modality and who sign the informed consent to participate in this study will be included.

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Impact on microbiota
timeFrame: 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 outcomes:
measure: Incidence of Acute graft versus host disease
timeFrame: From the day of transplant (Day 0) to Day +100 posttransplant
measure: Transplant related mortality
timeFrame: From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant
measure: Mortality caused by infection
timeFrame: From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant
measure: Incidence of severe infections
timeFrame: From the day of transplant (Day 0) to Day +30 posttransplant
measure: Overall survival
timeFrame: From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant
measure: Disease free survival
timeFrame: From the day of transplant (Day 0) to Days +30, +100 and +365 posttransplant
Other outcomes:
Locations:
city: Sevilla
country: Spain
facility: Virgen del Rocío University Hospital, Seville.
state: Seville
city: Madrid
country: Spain
facility: Gregorio Marañón University Hospital
city: Salamanca
country: Spain
facility: Salamanca University Hospital
city: Santander
country: Spain
facility: Marqués de Valdecilla University Hospital
city: Valencia
country: Spain
facility: University Clinical Hospital of Valencia
Study officials:
affiliation: Hematology Service, Hematopoietic Transplant Program, Seville Biomedicine Institute (IBIS) - Virgen del Rocío University Hospital, Seville.
name: Ildefonso Espigado, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
citation: Jimenez-Jorge S, Labrador-Herrera G, Rosso-Fernandez CM, Rodriguez-Torres N, Pachon-Ibanez ME, Smani Y, Marquez-Malaver FJ, Limon Ramos C, Solano C, Vazquez-Lopez L, Kwon M, Mora Barrios JM, Aguilar-Guisado M, Espigado I; GETH (Grupo Espanol de Trasplante Hematopoyetico y Terapia Celular). Assessing the impact on intestinal microbiome and clinical outcomes of antibiotherapy optimisation strategies in haematopoietic stem cell transplant recipients: study protocol for the prospective multicentre OptimBioma study. BMJ Open. 2020 Jul 20;10(7):e034570. doi: 10.1136/bmjopen-2019-034570.