Efficacy of a Probiotic or Fecal Microbiota Transplantation (FMT) on the Eradication of Rectal Multidrug-resistant Gram-negative Bacilli (MDR-GNB) Carriage (PROFTMDECOL)

NCT04431934 | Unknown DMC

• 1 other identifier: PI19/00842
• Study Type: interventional
• Target: 437
• Locations: 1 country
• Sites: 1

Brief Summary

The working hypothesis is that in patients who are rectal carriers of MDR-GNB (Multi drug-resistant gram negative bacilli), the rate and speed of eradication of the carrier status obtained with NAA regimens are insufficient and could be improved with additional interventions directed to restore a healthy fecal microbiota or to increase the colonization resistance by the putative beneficial activity of lactate-producing bacteria and bifidobacteria. A healthier colonic microbiota environment is expected not only to promote the eradication of the existing MDR organisms but also to hinder the subsequent recolonization and hopefully the risk of infection with gut dysbiosis -associated pathogens (MDR-GNB, C. difficile and Candida). The principal objective of the study is To compare the decolonization efficacy at the end of the study (60 ± 7 days after randomization) of the administration of a probiotic ("Vivomixx®" 2 sachets/12h for 2 weeks) versus the administration of two doses (administered a week apart) of a fecal microbiota transplantation preparation (equivalent to 50 g of healthy donor feces) and no treatment (control arm) in patients with rectal colonization with MDRGNB (ESBL-producing Klebsiella pneumoniae, CPE and MDR/XDR (multi drug-resistant/ extensively drug-resistant Pseudomonas aeruginosa).

Conditions

CARRIER STATE

Keywords

fecal microbiota transplantation; probiotics; carbapenemase-producing Enterobacteriaceae; multiple-drug resistant Pseudomonas aeruginosa; ESBl-producing Klebsiella pneumoniae

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with digestive decolonization rate

  Proportion of patients with digestive decolonization rate defined as negative rectal swab (RS) for the target MDR-GNB (ESBL-producing Klebsiella pneumoniae, CPE and MDR/XDR Pseudomonas aeruginosa) at the end of study (60 ± 7 days after the randomization).

  At the end of study (60 ± 7 days after the randomization).

Secondary Outcomes (6)

• Digestive decolonization rate defined as a negative fecal sample

  At the end of study treatment (3 weeks after randomization).

• Digestive decolonization rate defined as a negative rectal swab

  (week 1 after randomization).

• target MDR-GNB or any other MDR-GNB in any control RS or fecal sample

  through study completion, an average of 1 year

• clinical infections

  through study completion, an average of 1 year

• development of resistance to colistin or amikacin

  through study completion, an average of 1 year

Study Arms (3)

CONTROL

NO INTERVENTION

No intervention arm

PROBIOTIC

ACTIVE COMPARATOR

Dietary Supplement: PROBIOTIC

FMT REGIMEN

ACTIVE COMPARATOR

Dietary Supplement: FMT REGIMEN

Interventions

PROBIOTIC DIETARY_SUPPLEMENT

Participants assigned to the probiotic arm will receive 2 sachets of "Vivomixx®" dissolved in 50 L of warm water (according to the manufacturer indications) every 12 h orally or through a nasogastric tube (in this case the tube will be flushed with 50 mL of water after the administration). The probiotic will be started 24 h after the last dose of NAA and will be administered for 14 consecutive days. Each sachet of "Vivomixx®" contains a combination of 4 Lactobacillus (L. paracasei 24733, L. acidophilus 24735, L. delbrueckii ssp bulgaricus 24734, L. plantarum 24730), 3 Bifidobacteria (B. brief 24732, B. longum 24736, B. infantis 24737), and Streptococcus thermophilus 24731 at a concentration of 450 billion (45x1010) live lyophilized bacteria per sachet.

PROBIOTIC

FMT REGIMEN DIETARY_SUPPLEMENT

The FMT preparation will be administered as 2 doses, once a week, of 14-17 capsules per dose. Each dose (14-17 capsules) will contain the fecal microbiota equivalent to 50 gr of stools from a healthy donor. If the patient is carrying a nasogastric tube, the content of capsules will be decapsulized (\~27 gr of powder), diluted in 50 mL of water and passed through it, followed by the administration of 50 mL of water to flush the tube. The first dose will be administered 24 h after the last dose of NAA and the second dose one week later. Whenever possible, the two doses of FMT will be originated from the same donor. According to our data done by flow cytometry and bacterial culture in three replicates, each absorbate capsule contains approximately 1.12x1010 live bacteria.

FMT REGIMEN

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (≥18 years-old).
• Admitted to the Hospital Clinic of Barcelona with documented rectal colonization whitin the previous 7 days by rectal swabbing with MDR-GNB (ESBL-producing Klebsiella pneumoniae, carbapenemase-producing Enterobacterial (CPE) and MDR/XDR Pseudomonas aeruginosa).
• Eligible for routine digestive decolonization (7 days oral administration of nonabsorbable antibiotics (NAA).
• Capable to provide informed consent (by themselves or through their legal representatives).

You may not qualify if:

• Pregnant women or breastfeeding.
• Neutropenic patients (total neutrophil count \<500 cell/mm3)\*.
• HIV-infected patients with CD4(cluster of differentiation 4) count \<200 cell/mm3.
• Patients with active C. difficile infection.
• Patients with ileus or bowel obstruction.
• Patients with documented or suspected bowel perforation.
• Patients with a colistin-resistant MDR-GNB.

Sponsors & Collaborators

• Hospital Clinic of Barcelona: lead
• Fundacion Clinic per a la Recerca Biomédica: collaborator
• Institut d'Investigacions Biomèdiques August Pi i Sunyer: collaborator
• Fondo de Investigacion Sanitaria: collaborator

Study Sites (1)

Hospital Clinic

Barcelona, 08003, Spain

RECRUITING

Related Publications (26)

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MeSH Terms

Interventions

Probiotics

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Jose Antonio Martinez, PhD

  senior consultant

  PRINCIPAL INVESTIGATOR

• Ana del rio, PhD

  senior consultant

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jose Antonio JA Martinez, PhD

CONTACT

+34648521868; jamarti@clinic.cat

Fernanda Meira, MD

CONTACT

+34666368934; fandrade@clinic.cat

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Senior Consultor, Assistant Profesor of Medicine (University of Barcelona)

Model Details: This is an investigator-initiated, single center, parallel-group, randomized, open-label, clinical research with non pharmacological products.

Study Record Dates

• First Submitted: June 5, 2020
• First Posted: June 16, 2020
• Study Start: November 16, 2020
• Primary Completion: December 31, 2022
• Study Completion: July 1, 2023
• Last Updated: February 12, 2021

Record last verified: 2021-02

Locations

ES (1)