Probiotics to Actively Counter Ventilator Associated Pneumonia (PROACT)

NCT06092554 | Recruiting DMC

• 1 other identifier: 1336/CE-PROACT
• Study Type: interventional
• Target: 186
• Locations: 2 countries
• Sites: 9

Brief Summary

PROACT study aims to resolve uncertainties to influence actual practice guidelines or public health policing regarding VAP prevention in ICU by using probiotics administration. Multi-trauma patients with a head injury OR stroke or brain haemorrhage patients without any sign of aspiration and lung infection will be enrolled and randomized to either placebo or probiotic treatment to assess if VAP and mortality can be reduced in the interventional group.

Conditions

Ventilator Associated Pneumonia

Keywords

Ventilator Associated Pneumonia; Traumatic Brain Injury; stroke; probiotics; VAP; TBI

Outcome Measures

Primary Outcomes (1)

• Vap Incidence

  VAP is defined as first episode of lower respiratory tract infection that meets all the following criteria: (a) onset \>48 h after initiation of mechanical ventilation; (b) increase in SOFA score by ≥1 point; (c) new infiltrate in chest X-ray or chest computed tomography; (d) core temperature \>38°C; (e) purulent tracheobronchial secretions; (f) clinical pulmonary infection score (CPIS) \>6 ; and (g) isolation of a pathogen from BAL fluid (\>1 × 104 cfu/mL) or tracheal aspirate (\>1 × 105 cfu/mL) . This is analyzed for the ITT population. The ITT comprises the total of enrolled and randomized patients.

  45 days

Secondary Outcomes (6)

• Vap incidence analyzed for mITT

  45 days

• Sepsis

  45 days

• Septic shock

  45 days

• Catheter-related bloodstream infections (CRBSI)

  45 days

• ICU length of stay

  45 days

Study Arms (2)

Interventional: Probiotics

EXPERIMENTAL

Patients will receive a four probiotic preparation (LactoLevure, UniPharma, Athens, Greece).) in capsules containing: Lactobacillus acidophilus LA-5 \[1.75 × 109 colony-forming units (cfu)\], Lactobacillus plantarum (0.5 × 109 cfu), Bifidobacterium lactis BB12 (1.75 × 109 cfu) and Saccharomyces boulardii (1.5 × 109 cfu).

Dietary Supplement: LactoLevure

Control: Placebo

PLACEBO COMPARATOR

Patients will receive a placebo in capsules containing powdered glucose polymer.

Other: Placebo

Interventions

LactoLevure DIETARY_SUPPLEMENT

Patients will receive two capsules, twice daily for 30 days, one through the nasogastric tube and one spread on the oropharynx. The probiotic capsules look identical to the placebo capsules; the powder will be similar when opened. The capsule for nasogastric tube will be opened and suspended in 100 ml of tap water. The capsule for the oropharynx will be opened and suspended in sterile water based surgical lubricant. The administration must happen at least 30 minutes after oral antiseptic product usage (e.g. daily chlorhexidine oral care), which otherwise might neutralize the study supplement's action.

Interventional: Probiotics

Placebo OTHER

Patients will receive two capsules, twice daily for 30 days, one through the nasogastric tube and one spread on the oropharynx. The placebo capsules contain a powdered glucose polymer that is unharmful for the patient and will be provided by the sponsor. The placebo capsules look identical to the probiotic capsules; the powder will be similar when opened. The capsule for nasogastric tube will be opened and suspended in 100 ml of tap water. The capsule for the oropharynx will be opened and suspended in sterile water based surgical lubricant. The administration must happen at least 30 minutes after oral antiseptic product usage (e.g. daily chlorhexidine oral care), which otherwise might neutralize the study supplement's action.

Control: 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 aged 18-80 years
• at least one of the following conditions: a) recent trauma involving head injury and at least one more organ system; b) stroke or brain hemorrhage without any sign of aspiration and lung infection
• likelihood that the duration of mechanical ventilation would be at least six days
• written informed consent provided by the patient or legal representative

You may not qualify if:

• has received mechanical ventilation more than 72 hours from start of screening
• pregnancy or Lactation
• patients at risk of iatrogenic probiotic infection e.g. immunosuppression which includes
• HIV \<200 CD4 cells/μL
• those receiving chronic immunosuppressive medications (e.g., azathioprine, cyclosporine, cyclophosphamide, tacrolimus, methotrexate, mycofenolate, Anti-IL2)
• previous transplantation at any time
• malignancy requiring chemotherapy in the last 3 months
• neutropenia \[absolute neutrophil count \< 500\])
• patients with a primary diagnosis of severe pancreatitis (Ranson score of 3 or more). Mild and moderate pancreatis is not excluded
• ischemic bowel disease
• oropharyngeal mucosal injury
• inability to receive enteral medications
• intent to withdraw advanced life support as per ICU doctor in charge
• patients at risk of endovascular infection which includes
• previously documented rheumatic heart disease, congenital valve disease, surgically repaired congenital heart disease, unrepaired cyanotic congenital heart disease, any intracardiac repair with prosthetic material \[mechanical or bioprosthetic cardiac valves\]

Sponsors & Collaborators

• University of Bari: lead
• Uni-Pharma: collaborator

Study Sites (9)

Hospital Erasme

Brussels, Belgium

RECRUITING

Regional General Hospital F. Miulli

Acquaviva delle Fonti, BA, Italy

RECRUITING

Intensive Care Unit, Policlinico di Bari

Bari, BA, Italy

RECRUITING

Azienda Ospedaliero Universitaria di Alessandria SS. Antonio e Biagio e Cesare Arrigo

Alessandria, Italy

RECRUITING

Ospedale Di Venere

Bari, 70131, Italy

RECRUITING

AUSL Bologna Ospedale Bellaria

Parma, Italy

RECRUITING

Azienda Ospedaliero Universitaria di Parma

Parma, Italy

RECRUITING

Azienda Ospedaliera di Perugia

Perugia, Italy

RECRUITING

Azienda ospedaliera Santa Maria di Terni

Terni, Italy

RECRUITING

Related Publications (1)

• Corriero A, Soloperto R, Giglio M, Salvagno M, Trerotoli P, Grasso S, Ribezzi M, Mosca A, Petrillo C, De Toma N, Magnesa G, Giacomucci A, Accattoli R, Gadaleta RM, Florio M, Cariello M, Moschetta A, Puntillo F, Taccone FS, Ranieri VM. Probiotics to reduce ventilator-associated pneumonia in adults with acute non-anoxic brain injury: Study Protocol for a Double-Blind Multicenter Randomized International Clinical Trial (PROACT). Trials. 2025 Nov 10;26(1):484. doi: 10.1186/s13063-025-09230-w.

  PMID: 41214813 DERIVED

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated; Brain Injuries, Traumatic; Stroke

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Filomena Puntillo, MD, PhD

  University of Bari

  STUDY DIRECTOR

• Alberto Corriero, MD

  University of Bari

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alberto Corriero, MD

CONTACT

+393280072443; alberto.corriero@gmail.com

Filomena Puntillo, MD, PhD

CONTACT

+390805594237; filomena.puntillo@uniba.it

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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: The present study will be a multicenter, randomized, double-blind, placebo-controlled trial. Allocation will rely on a computer-based random number generator provided in a sequentially numbered, sealed, opaque envelope.

Study Record Dates

• First Submitted: October 15, 2023
• First Posted: October 23, 2023
• Study Start: December 13, 2023
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): July 15, 2026
• Last Updated: September 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (8); BE (1)