GRam Stain-guided Antibiotics ChoicE for Ventilator-Associated Pneumonia (GRACE-VAP) Trial

Osaka General Medical Center

Status and phase: Completed; Phase 4

Conditions: Ventilator Associated Pneumonia

Treatments: Drug: Gram stain-guided antibiotic choice; Drug: Guidelines-based antibiotics choice

Study type: Interventional

Funder types: Other

Identifiers

NCT03506113

29-C0707

UMIN000031933 (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment: 206 patients

Sex: All

Ages: 15+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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206 participants in 2 patient groups

Gram stain-guided therapy group

Active Comparator group

Description:

The results of Gram staining of endotracheal aspirate are used to guide the selection of antibiotics. The results of the Gram stains are categorised as Gram-positive cocci (GPC) chains, GPC clusters, Gram-positive bacilli (GPB), Gram-negative rods (GNR), or a combination of these. A non-pseudomonal beta-lactam antibiotic is selected when the Gram stain of the endotracheal aspirate shows only GPC chains and/or GPB. An anti-MRSA agent is selected when the Gram stain results show GPC clusters without GNR. An anti-pseudomonal agent is selected when the Gram stain results show GNR without GPC clusters. The combination of an anti-pseudomonal agent and an anti-MRSA agent is selected when the Gram stain results show both GPC clusters and GNR.

Treatment:

Drug: Gram stain-guided antibiotic choice

Guidelines-based therapy group

Active Comparator group

Description:

Patients are administered the combination of an anti-pseudomonal agent and anti-MRSA agent according to the Infectious Disease Society of America and the American Thoracic Society (IDSA/ATS) guidelines because 47.7% of S. aureus isolates are MRSA in Japanese ICUs

Treatment:

Drug: Guidelines-based antibiotics choice