NCT03506113

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

Completed Phase 4 Last updated 21 September 2022

What this trial tests

Phase 4 trial testing Gram stain-guided antibiotic choice in Ventilator Associated Pneumonia in 206 participants. Completed in 28 June 2020.

Timeline

1 April 2018

Primary endpoint
28 June 2020

28 June 2020

Quick facts

Lead sponsor	Osaka General Medical Center
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	206
Start date	1 April 2018
Primary completion	28 June 2020
Estimated completion	28 June 2020
Sites	12 locations across Japan

Drugs / interventions tested

• Gram stain-guided antibiotic choice — full drug profile →
• Guidelines-based antibiotics choice — full drug profile →

Conditions studied

• Ventilator Associated Pneumonia — all drugs for Ventilator Associated Pneumonia →

Sponsor

Osaka General Medical Center

Who can join

15 and older, any sex, with Ventilator Associated Pneumonia. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Effect of Gram Stain-Guided Initial Antibiotic Therapy on Clinical Response in Patients With Ventilator-Associated Pneumonia: The GRACE-VAP Randomized Clinical Trial.
   Yoshimura J, Yamakawa K, Ohta Y, Nakamura K, et al · · 2022 · cited 37× · PMID 35394515 · DOI 10.1001/jamanetworkopen.2022.6136
2. ESICM LIVES 2020.
   · 2020 · cited 13× · PMID 33313986 · DOI 10.1186/s40635-020-00354-8
3. GRam stain-guided Antibiotics ChoicE for Ventilator-Associated Pneumonia (GRACE-VAP) trial: rationale and study protocol for a randomised controlled trial.
   Yoshimura J, Yamakawa K, Kinoshita T, Ohta Y, et al · · 2018 · cited 7× · PMID 30409160 · DOI 10.1186/s13063-018-2971-2
4. Gram stain-guided antibiotic choice: a GRACEful method to safely restrict overuse of broad-spectrum antibiotic agents.
   Yoshimura J, Yamakawa K, Kinoshita T, Fujimi S. · · 2018 · cited 6× · PMID 30547826 · DOI 10.1186/s13054-018-2270-z