Probiotic Prophylaxis for Microbiome Modulation and VAP or Infections Prevention in Multitrauma Patients

NCT03074552 | Completed

• 1 other identifier: ProVAP
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

Ventilator-associated pneumonia (VAP), is a type of pneumonia that develops more than 48 hours after endotracheal intubation, is common in intensive care units (ICUs). It is estimated to be responsible for 27% to 47% of ICU-acquired infections. The pathogenesis of VAP is complex but typically involves colonization of the aerodigestive tract with pathogenic bacteria, the formation of biofilms, and microaspiration of contaminated secretions. Preventing carriage of potentially pathogenic micro-organisms from the aerodigestive tract is an infection control strategy used to reduce the occurrence of VAP. One novel intervention is the administration of prophylactic probiotics which restore non-pathogenic flora that compete with pathogens, modulate local and systemic immunity, and decrease intestinal permeability and thus can be beneficial in preventing nosocomial infections in critically ill patients. The role of the probiotics in preventing VAP in mechanically ventilated patients is inconclusive. Some evidence indicates that probiotics may reduce the incidence of VAP by inhibiting pathogen adhesion, improving gut mucosal barrier function, reducing bacterial translocation and up-regulating the immune system. Furthermore, guidelines remain inconclusive regarding the role of commensal oropharyngeal flora (COF) as a causative agent in VAP, mainly due to a scarcity of studies in this research field. However, there is evidence that COF may cause pulmonary infection, mostly in immunocompromised patients.

Conditions

Ventilator Associated Pneumonia; Infection; Trauma

Keywords

probiotics; VAP; microbiome; trauma; infections

Outcome Measures

Primary Outcomes (1)

• Probiotics for VAP prophylaxis

  To determine the efficacy of probiotic administration for the prophylaxis of VAP in a multi trauma population admitted in the ICU This outcome will be assessed by the difference of number of cases (n) and percentage of change (%) in VAP development between probiotics and control groups Ventilator associated pneumonia (VAP) will be defined as pneumonia developing more than 48 h after endotracheal intubation and initiation of mechanical ventilation. The diagnostic criteria for VAP will be the following: * SOFA score elevation of at least 1 point * New or progressive radiographic consolidation or infiltrate. In addition, at least 2 of the following: * Temperature \> 38 °C * Leukocytosis (white blood cell count ≥ 12,000 cells/ mm3) or leukopenia (white blood cell count \< 4,000 cells/mm3) * Presence of purulent secretions * BAL \> 104 colony forming units (CFU)/ml)

  30 days

Secondary Outcomes (2)

• Probiotics for indections control

  30 days

• Probiotics for bacteremia, sepsis or septic shock reduction

  30 days

Other Outcomes (1)

• Impact of Probiotics use on parameters related to hospitalization and mortality

  30 days

Study Arms (2)

Probiotics

EXPERIMENTAL

The probiotic preparation \[ LactoLevure\] will consist a combination of four probiotics.

Dietary Supplement: LactoLevure

Placebo

PLACEBO COMPARATOR

Placebo will consist of identical capsules of powdered glucose polymer, and they will be constructed by the same industry that manufactures the probiotics capsules.

Other: Placebo

Interventions

LactoLevure DIETARY_SUPPLEMENT

The probiotic preparation will consist a combination of four probiotics: Lactobacillus acidophilus LA-5 1.75 × 109 CFU, Lactobacillus Plantarum 0.5 × 109 CFU, Bifidobacterium lactis BB-12 1.75 × 109 CFU και Saccharomyces boulardii 1.5 × 109 CFU per capsule (LactoLevure, UniPharma, Athens, Greece).

Probiotics

Placebo OTHER

Placebo will consist of identical capsules of powdered glucose polymer

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• adults \>18 and \< 80 years oldmultitrauma patients with at least two organ-system injury
• intubated immediately after injury
• likelihood that the patient would require mechanical ventilation with an endotracheal tube (or tracheostomy) for \>10 days
• life expectancy \> 15 days

You may not qualify if:

• investigators unable to obtain informed written consent from patients' relatives
• administer the first dose of the study drug within 24 hours of intubation
• pregnancy; lactation; immunosuppression; hematologic disease; prosthetic cardiac valve or vascular graft; cardiac trauma; history of rheumatic fever, endocarditis, or congenital cardiac abnormality; oropharyngeal mucosal injury; recent history of sinusitis and respiratory tract infection
• obesity \[BMI \> 40\]
• administration of antibiotics for \> 3 days before recruitment into the study
• administration of probiotics before recruitment into the study
• history of infection from Hepatis B or C and HIV
• administration of \< 90% of the predicted doses of probiotics during the study period

Sponsors & Collaborators

• Aristotle University Of Thessaloniki: lead
• Uni-Pharma: collaborator

Study Sites (1)

AHEPA University Hospital

Thessaloniki, 56346, Greece

Location

Related Publications (9)

• Scholte JB, van der Velde JI, Linssen CF, van Dessel HA, Bergmans DC, Savelkoul PH, Roekaerts PM, van Mook WN. Ventilator-associated Pneumonia caused by commensal oropharyngeal Flora; [corrected] a retrospective Analysis of a prospectively collected Database. BMC Pulm Med. 2015 Aug 12;15:86. doi: 10.1186/s12890-015-0087-y.

  PMID: 26264828 BACKGROUND

• Wang J, Liu KX, Ariani F, Tao LL, Zhang J, Qu JM. Probiotics for preventing ventilator-associated pneumonia: a systematic review and meta-analysis of high-quality randomized controlled trials. PLoS One. 2013 Dec 18;8(12):e83934. doi: 10.1371/journal.pone.0083934. eCollection 2013.

  PMID: 24367620 BACKGROUND

• Zeng J, Wang CT, Zhang FS, Qi F, Wang SF, Ma S, Wu TJ, Tian H, Tian ZT, Zhang SL, Qu Y, Liu LY, Li YZ, Cui S, Zhao HL, Du QS, Ma Z, Li CH, Li Y, Si M, Chu YF, Meng M, Ren HS, Zhang JC, Jiang JJ, Ding M, Wang YP. Effect of probiotics on the incidence of ventilator-associated pneumonia in critically ill patients: a randomized controlled multicenter trial. Intensive Care Med. 2016 Jun;42(6):1018-28. doi: 10.1007/s00134-016-4303-x. Epub 2016 Apr 4.

  PMID: 27043237 BACKGROUND

• Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.

  PMID: 26903338 BACKGROUND

• Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS, Angus DC, Rubenfeld GD, Singer M; Sepsis Definitions Task Force. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):775-87. doi: 10.1001/jama.2016.0289.

  PMID: 26903336 BACKGROUND

• Kotzampassi K, Giamarellos-Bourboulis EJ. Probiotics for infectious diseases: more drugs, less dietary supplementation. Int J Antimicrob Agents. 2012 Oct;40(4):288-96. doi: 10.1016/j.ijantimicag.2012.06.006. Epub 2012 Aug 2.

  PMID: 22858373 BACKGROUND

• Stavrou G, Giamarellos-Bourboulis EJ, Kotzampassi K. The role of probiotics in the prevention of severe infections following abdominal surgery. Int J Antimicrob Agents. 2015 Dec;46 Suppl 1:S2-4. doi: 10.1016/j.ijantimicag.2015.10.003.

  PMID: 26686273 BACKGROUND

• Kotzampassi K, Stavrou G, Damoraki G, Georgitsi M, Basdanis G, Tsaousi G, Giamarellos-Bourboulis EJ. A Four-Probiotics Regimen Reduces Postoperative Complications After Colorectal Surgery: A Randomized, Double-Blind, Placebo-Controlled Study. World J Surg. 2015 Nov;39(11):2776-83. doi: 10.1007/s00268-015-3071-z.

  PMID: 25894405 BACKGROUND

• Giamarellos-Bourboulis EJ, Bengmark S, Kanellakopoulou K, Kotzampassi K. Pro- and synbiotics to control inflammation and infection in patients with multiple injuries. J Trauma. 2009 Oct;67(4):815-21. doi: 10.1097/TA.0b013e31819d979e.

  PMID: 19820590 BACKGROUND

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated; Infections; Wounds and Injuries

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Katerina Kotzampassi, MD, PhD

  Aristotle University Of Thessaloniki

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A numbered sealed envelope will be used to ensure blinding. Only the pharmacist responsible for the sealed envelopes preparation will be aware of its content, with no further involvement in the study protocol.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: The present study will be a multicenter, randomized, double-blind, placebo-controlled trial including data collected from 9 ICUs. Patients will be randomly assigned in a 1:1 ratio to receive probiotic or placebo treatment according to a computer-based table blinded to study investigators and physicians in charge.

Study Record Dates

• First Submitted: February 25, 2017
• First Posted: March 9, 2017
• Study Start: August 19, 2017
• Primary Completion: November 15, 2020
• Study Completion: December 15, 2020
• Last Updated: August 31, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)