Combined Use of a Respiratory Multiplex PCR and Algorithm-based Therapy to Improve Early Optimization of Antibiotic Therapy in Critically Ill Patients With Ventilator-associated Pneumonia (SMART-VAP)

Combined Use of a Respiratory Multiplex PCR and Algorithm-based Therapy to Improve Early Optimization of Antibiotic Therapy in Critically Ill Patients With Ventilator-associated Pneumonia : a Bicentric, Parallel-group, Randomized Controlled Trial.

Assess the impact of a strategy combining respiratory mPCR and algorithm-based therapy developed using local epidemiology on the early optimization of initial antibiotic therapy for ventilator-associated pneumonia (VAP) (intervention), compared to a conventional strategy (control).

A bicentric, parallel-group, randomized controlled trial. The primary assessment criterion is the proportion of early optimized antibiotic therapy within 24 hours of respiratory sampling.

Study Overview

• Status: Not yet recruiting
• Conditions: Ventilator Associated Pneumonia ( VAP)
• Intervention / Treatment: Procedure: strategy combining respiratory mPCR and algorithm-based therapy developed using local epidemiology

Detailed Description

In both arms, for eligible patients with VAP, a deep respiratory sample collection is performed prior to inclusion. This collection is carried out either by mini bronchoalveolar lavage (BAL) via bronchoscopy or by blind mini BAL in alignment with the protocolized procedure. Initial antibiotic therapy is initiated after the deep sample has been taken according to the discretion of the attending clinician and in accordance with good practice recommendations. Both groups have their samples analyzed using conventional techniques. First, there is a direct examination, followed by culture and susceptibility testing, which is used as the gold standard technique for evaluating the primary endpoint.

In the intervention arm, in addition to conventional techniques, a broad-panel respiratory mPCR is performed before the 12th hour following achievement of the deep respiratory sample on the collected BAL. Once the mPCR results are received, the clinician adjusts the initial antibiotic therapy using algorithm-based therapy developed using local epidemiology in order to optimize treatment as early as possible.

In the control arm, the strategy is based on the clinician's choice in accordance with best practice recommendations without the combined use of respiratory mPCR and algorithm-based therapy. The deep respiratory sample is analyzed using conventional methods. Initial antibiotic treatment is therefore adapted by the clinician in charge of the patient according to departmental practices based on best practice recommendations, taking into account the results of the direct examination, culture, and susceptibility testing.

• Study Type: Interventional
• Enrollment (Estimated): 124
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hugo MARTINIERE, PH; Phone Number: +33 4 66 68 33 31; Email: hugo.martiniere@chu-nimes.fr

Study Locations

• France
  • Nîmes, France, 34070
    • CHU Nîmes
    • Contact: Hugo Martiniere, PH; Phone Number: + 33 6 68 68 33 31; Email: hugo.martiniere@chu-nimes.fr
    • Principal Investigator: Hugo Martiniere, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults (≥18 years) with VAP (mechanical ventilation and hospitalization ≥ 48 hours) and deep respiratory sample by mini BAL < 12 hours. The diagnosis of pneumonia includes two clinical criteria among fever (≥38.3°C), purulent sputum or aspiration, hyperleukocytosis (>12,000 WBC/mm³) or leukopenia (<4,000 WBC/mm³), hypoxemia, auscultatory signs in the affected area, and a newly-appeared parenchymal infiltrate
• Patient receiving initial probabilistic antibiotic therapy for VAP suspicion
• Informed consent or emergency procedure
• Patient affiliated with or beneficiary of a health insurance plan.

Non inclusion Criteria:

• Pregnancy
• Congenital immunodeficiency;
• HIV infection with the lymphocyte CD4 count below 200/mm3 or unknown in the last year;
• Acute hematologic malignancy;
• Neutropenia (<1 leucocyte/mL or < 0.5 neutrophil/mL);
• Immunosuppressive drugs within the previous 30 days, including anti-cancer - Chemotherapy and anti-rejection drugs for organ/bone marrow transplant
• Corticosteroids ≥ 20 mg/d of prednisone equivalent for more than 14 days
• Known allergy to beta-lactams
• Moribund patient or death expected from underlying disease during the current admission;
• Patient deprived of liberty or under legal protection measure;
• Participation in another interventional trial.

Exclusion criteria :

• mPCR non available

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: combined use of mPCR and algorithm-based therapy; strategy combining respiratory mPCR on a deep respiratory sample obtained by mini bronchoalveolar lavage and algorithm-based therapy developed using local epidemiology	Procedure: strategy combining respiratory mPCR and algorithm-based therapy developed using local epidemiology; strategy combining respiratory mPCR carried out either by mini bronchoalveolar lavage (BAL) via bronchoscopy or by blind mini BAL, and algorithm-based therapy developed using local epidemiology for the early optimization of initial antibiotic therapy
No Intervention: Conventional strategy for antibiotic therapy at discretion of ICU physicians; The conventional strategy is based on the clinician's choice in accordance with best practice recommendations, without the combined use of respiratory mPCR and algorithm-based therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effectiveness of a combined use a broad panel respiratory mPCR and an algorithm-based therapy developed using local epidemiology on the early optimization of initial antibiotic therapy for VAP, as compared to a conventional strategy	Proportion of patients receiving optimized antibiotic therapy defined as effective antibiotic therapy and for which antibiotic de-escalation, when recommended, was performed early, within 24 hours after deep respiratory sampling.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of exposure to broad-spectrum antibiotic therapy.	Average number of days of broad-spectrum antibiotic administration per patient at day 28	Day 28
Compare expected and actual time frames for optimizing antibiotic therapy in the two arms.	Time in hours between deep respiratory sampling and optimization of antibiotic therapy.	day 28
Mechanical ventilation at day 28	mechanical ventilation free-days at day 28	day 28
lenght of stay in ICU at day 28	ICU free-days at day 28	day 28
Number of organ-failure free days (based on SOFA) at day 28	Number of organ-failure free days (based on SOFA) at day 28	day 28
Mortality at day 28	Mortality at 28	day 28
Sensitivity, specificity, and likelihood ratios of the broad panel mPCR Film Array for the diagnosis of pneumonia, taking the conventional microbiological tests as reference	Sensitivity, specificity, and likelihood ratios of the broad panel mPCR Film Array for the diagnosis of pneumonia, taking the conventional microbiological tests as reference	day 28
Incidence rates of infection or colonization with multidrug resistant bacteria and Clostridium difficile infections at day 28	Incidence rates of infection or colonization with multidrug resistant bacteria and Clostridium difficile infections at day 28	day 28
Quantify early antibiotic de-escalation in the two groups under study	Early and broad-spectrum antibiotic sparing according to the modified Antibiotic Spectrum Index (ASIm) de-escalation score (from No antibiotics (0) to very broad (≥8))	day 1 and day 7
Rate of Clinical Cure at Day	use test of cure at day 7	day 7
Cost of the total hospital admissions	Total Hospitalization Cost per Participant at Day 28 (Including ICU Stay, Antimicrobial Therapy, Microbiological Diagnostic Workup, and Infection Relapse Costs)	day 28

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: February 4, 2026
• First Submitted That Met QC Criteria: February 4, 2026
• First Posted (Actual): February 11, 2026

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 11, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: ventilator associated pneumonia; mPCR; algorithm-based therapy
• Additional Relevant MeSH Terms: Healthcare-Associated Pneumonia; Pathologic Processes; Disease Attributes; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Cross Infection; Iatrogenic Disease; Pathological Conditions, Signs and Symptoms; Pneumonia, Ventilator-Associated
• Other Study ID Numbers: 2025-A02343-46

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No