Ventilator Associated Pneumonia
Conditions
Keywords
Gram staining, Antimicrobial therapy, Empirical therapy, Nosocomial infection, Mechanical ventilation, Intensive care, Sepsis
Brief summary
Background: Optimising the use of antibiotic agents is a pressing challenge to overcoming the rapid emergence and spread of multidrug-resistant pathogens in intensive care units (ICUs). Although Gram staining may possibly provide immediate information for predicting pathogenic bacteria, Gram stain-guided initial antibiotic treatment is not well established in the ICU setting. The investigators planned the GRam stain-guided Antibiotics ChoicE for Ventilator-Associated Pneumonia (GRACE-VAP) trial to investigate whether Gram staining can safely restrict the use of broad-spectrum antibiotics in patients with ventilator-associated pneumonia (VAP), which is one of the most common hospital-acquired infections in ICUs. Methods/Design: The GRACE-VAP trial is a multicenter, randomised, open-label parallel-group trial to assess the non-inferiority of Gram stain-guided initial antibiotic treatment to guidelines-based initial antibiotic treatment for the primary endpoint of clinical cure rate in patients with VAP. Secondary endpoints include the coverage rates of initial antibiotic therapies, the selected rates of anti-pseudomonal agents and anti-methicillin-resistant Staphylococcus aureus (MRSA) agents as initial antibiotic therapies, 28-day all-cause mortality, ICU-free days, ventilator-free days, and adverse events. Participants are randomly assigned to receive Gram stain-guided treatment or guidelines-based treatment at a ratio of 1:1. In the Gram stain group, results of Gram staining of endotracheal aspirate are used to guide the selection of antibiotics. In the guidelines group, the combination of an anti-pseudomonal agent and anti-MRSA agent are administered. A total sample size of 200 was estimated to provide a power of 80% with a 1-sided alpha level of 2.5% and a non-inferiority margin of 20%, considering 10% non-evaluable participants. Discussion: The GRACE-VAP trial is expected reveal whether Gram staining can reduce the use of broad-spectrum antibiotics without impairing patient outcomes and thereby provide evidence for an antibiotics selection strategy in patients with VAP.
Interventions
DRUGGram stain-guided antibiotic choice
The results of Gram staining of endotracheal aspirate are used to guide the selection of antibiotics.
DRUGGuidelines-based antibiotics choice
Patients are administered the combination of an anti-pseudomonal agent and anti-MRSA agent according to IDSA/ATS guidelines
Sponsors
Chukyo Hospital
Ebina General Hospital
Hitachi General Hospital
Kansai Medical University
Kansai Medical University Medical Center
Nagasaki University
Saga University
University of the Ryukyus
Wakayama Medical University
Tajima Emergency and Critical Care Medical Center
Sapporo City General Hospital
Osaka General Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients undergoing mechanical ventilation in the ICU * Patients undergoing mechanical ventilation for at least 48 hours * Patients diagnosed as having VAP, which is defined by a modified clinical pulmonary infection score of 5 or more
Exclusion criteria
* Patients having an allergy to study medications * Pregnant patients * Patients discharged from ICU * Patients diagnosed as having heart failure or atelectasis * Patients administered antibiotics for more than 24 hours when they meet the inclusion criteria * Patients declined to provide full life support * Patients judged as inappropriate at the discretion of the study physician.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical cure of VAP | up to 22 days | Cure is defined as completion of antibiotic therapy within 14 days, improvement or lack of progression of baseline radiographic findings at the end of therapy (EOT), and resolution of signs and symptoms of pneumonia at the follow-up/test of cure visit (FU/TOC) conducted 7 days after EOT. Failure is defined as administration of study medication for 15 days or more, progression of radiological signs of pneumonia at EOT, or relapsed pneumonia at FU/TOC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Select of anti-MRSA agents as initial antibiotic therapies | on day 1 | — |
| Coverage of initial antibiotic therapies | on day 1 | Therapies will be considered appropriate when all pathogens isolated with at least 1+ semi-quantitative growth from endotracheal aspirates are covered by the selected antibiotic agents. |
| 28-day mortality | up to 28 days | — |
| ICU-free days | up to 28 days | — |
| Ventilator-free days | up to 28 days | — |
| Select of anti-pseudomonal agents as initial antibiotic therapies | on day 1 | — |
| Need of escalation or de-escalation of antibiotic therapies | up to 28 days | The investigators evaluate whether antibiotic agents are changed during the treatments of VAP. |
| Adverse events related to antibiotics | up to 7 days after the end of therapy | renal impairment, thrombocytopenia, diarrhoea, Clostridium difficile infection, skin rash, and seizure |
| Inflammation marker | up to 14 days | Laboratory marker of inflammation (CRP, PCT) on 2, 4, 6, 8, and 14 days |
| Organ failure control | up to 14 days | The investigators evaluate Sequential Organ Failure Assessment (SOFA) score on 2, 4, 6, 8, and 14 days. The SOFA score is made of 6 variables, each representing an organ system ( respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems). Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure). The total SOFA score is calculated by the sum of each 6 variables (range, 0-24). |
| Renal function | up to 14 days | The investigators evaluate whether participants are performed a renal replacement therapy. |
| Duration of antibiotic therapies | up to 28 days | — |
Countries
Japan
Outcome results
None listed