Clinical Trial to Demonstrate the Effectiveness of Fecal Microbiota Transplantation for Selective Intestinal Decolonization of Patients Colonized by Carbapenemase-producing Klebsiella Pneumoniae

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Carbapenemase-producing Enterobacteriaceae Infection

Intervention / Treatment
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* Biological: Fecal microbiota transplantation
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fecal microbiota transplantation<br> | Biological: Fecal microbiota transplantation<br>* Patients will receive four fecal microbiota transplantation (FMT) capsules. Microbiota is obtained from healthy patients.<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Patients will receive four oral capsules containing placebo. These capsules will have the same shape, weight and colour as capsules containing FMT.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decolonization | Percentage of patients with intestinal decolonization after receiving oral capsules of FMT or placebo in intention to treat population. | 30 days after treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with adverse effects | Percentage of patients with adverse effects | 90 days after treatment. | 
| Bacterial load | Amount of KPC-producing Klebsiella pneumoniae (Kp-KPC) after intervention | 7 days and 30 days after treatment. | 
| Persistent intestinal decolonization | Persistence of intestinal decolonization 90 days after intervention | 90 days after treatment. | 
| Infections caused by Kp-KPC | Percentage of patients with infections caused by Kp-KPC after intervention | 90 days after treatment. | 
| Mortality | Percentage of patients died after intervention | 90 days after treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fecal microbiota transplantation, Klebsiella pneumoniae, carbapenemase, intestinal colonization, decolonization