Clinical trial NCT04760665: Clinical Trial to Demonstrate the Effectiveness of Fecal Microbiota Transplantation for Selective Intestinal Decolonization of Patients Colonized by Carbapenemase-producing Klebsiella Pneumoniae
Official title: Randomized, Superiority, Double Blind Controlled With Placebo, Clinical Trial, to Demonstrate the Effectiveness of Fecal Microbiota Transplantation for Selective Intestinal Decolonization of Patients Colonized by Klebsiella Pneumoniae Carbapenemase (KPC)-Producing
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Carbapenemase-producing Enterobacteriaceae Infection
Keywords: fecal microbiota transplantation
Klebsiella pneumoniae
carbapenemase
intestinal colonization
decolonization
Lead sponsor: Maimónides Biomedical Research Institute of Córdoba
Sponsor class: OTHER
Collaborators: name: Mikrobiomik Healthcare Company S.L.
First posted: 2021-02-18
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Infections caused by carbapenemase-producing Enterobacteriaceae are frequent and often associated with high rates of mortality. Colonized patients are at increased risk of infection for these microorganisms. Moreover, they can act as a reservoir facilitating the transmission to other patients. To date, decolonization strategies with antibiotics have not obtained convincing results. For that reason our main objective is to investigate the efficacy of fecal microbiota transplantation (FMT) for selective intestinal decolonization of patients colonized by KPC-producing Klebsiella pneumoniae (Kp-KPC) at 30 days after FMT. Our hypothesis is that FMT is effective and safe for selective intestinal decolonization in patients colonized by Kp-KPC. The design of the study is a randomized, superiority, double blind controlled with placebo clinical trial.

The main variable is the percentage of patients with intestinal decolonization at 30 days after FMT in intention to treat population (all randomized patients). Decolonization will be considered as the abscence of isolation of Kp-KPC in culture from rectal swab together with the abscence of detection of carbapenemase by mean of polymerase chain reaction.

Secondary objectives are:

* To evaluate the safety of FMT.
* To determine if FMT is associated with decrease in the amount of bacteria at 7 days after FMT and 30 days after FMT.
* To evaluate if FMT is associated with persistent intestinal decolonization at 3 months after intervention.
* To study if FMT is associated with decrease in the incidence of Kp-KPC infections at 3 months after intervention.
* To evaluate if FMT is associated with decrease in mortality due to Kp-KPC infections at 3 months after intervention.


Eligibility criteria: Inclusion Criteria:

* Age\> = 18 years.
* Signature of the informed consent by the patient or legally designated person
* Absence of active infection by carbapenemase-type KPC-producing Klebsiella pneumoniae at the time of assessment as well as in the month prior to inclusion in the study

Exclusion Criteria:

* Terminal situation, or estimated life expectancy of less than 3 months
* Pregnant or lactating women
* Intolerance or inability to take oral medication at the time of assessment
* History of aspiration or dysphagia
* Patients with a history of colectomy, colostomy or ileostomy
* Patients who are receiving or have received antibiotics in the month prior to the inclusion assessment
* Neutrophil count less than 500 cells / mm3
* Anticipation of the use of myelosuppressive treatment (eg. dexamethasone, chemotherapy against to solid tumors or prior to transplantation of hematopoietic progenitories) within 30 days after inclusion in the study
* Hematopoietic stem cell transplantation in the month prior to inclusion in the study
* Presence of clinical signs of mucositis
* Forecast of major abdominal surgical intervention in the month following inclusion in the study
* Patients with a Gianella Score\> 12 points
* History of having received decolonization guidelines in the previous 3 months
* Severe food allergy

Primary outcomes:
measure: Decolonization
timeFrame: 30 days after treatment.
Secondary outcomes:
measure: Percentage of patients with adverse effects
timeFrame: 90 days after treatment.
measure: Bacterial load
timeFrame: 7 days and 30 days after treatment.
measure: Persistent intestinal decolonization
timeFrame: 90 days after treatment.
measure: Infections caused by Kp-KPC
timeFrame: 90 days after treatment.
measure: Mortality
timeFrame: 90 days after treatment.
Other outcomes:
Locations:
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofía
Study officials:
affiliation: Hospital Universitario Reina Sofía
name: Juan José Castón Osorio, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Reina Sofía
name: Ángela Cano Yuste, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Perez-Nadales E, Cano A, Recio M, Artacho MJ, Guzman-Puche J, Doblas A, Vidal E, Natera C, Martinez-Martinez L, Torre-Cisneros J, Caston JJ. Randomised, double-blind, placebo-controlled, phase 2, superiority trial to demonstrate the effectiveness of faecal microbiota transplantation for selective intestinal decolonisation of patients colonised by carbapenemase-producing Klebsiella pneumoniae (KAPEDIS). BMJ Open. 2022 Apr 6;12(4):e058124. doi: 10.1136/bmjopen-2021-058124.