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

NCT ID: NCT03506113

Last Updated: 2022-09-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

206 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-01

Study Completion Date

2020-06-28

Brief Summary

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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.

Detailed Description

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Conditions

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Ventilator Associated Pneumonia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Gram stain-guided therapy group

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.

Group Type ACTIVE_COMPARATOR

Gram stain-guided antibiotic choice

Intervention Type DRUG

The results of Gram staining of endotracheal aspirate are used to guide the selection of antibiotics.

Guidelines-based therapy group

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

Group Type ACTIVE_COMPARATOR

Guidelines-based antibiotics choice

Intervention Type DRUG

Patients are administered the combination of an anti-pseudomonal agent and anti-MRSA agent according to IDSA/ATS guidelines

Interventions

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Gram stain-guided antibiotic choice

The results of Gram staining of endotracheal aspirate are used to guide the selection of antibiotics.

Intervention Type DRUG

Guidelines-based antibiotics choice

Patients are administered the combination of an anti-pseudomonal agent and anti-MRSA agent according to IDSA/ATS guidelines

Intervention Type DRUG

Eligibility Criteria

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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

* Patients declined to provide full life support
* Patients judged as inappropriate at the discretion of the study physician.

Exclusion Criteria

* Patients having an allergy to study medications
* Pregnant patients
* Patients discharged from ICU
* Patients diagnosed as having heart failure or atelectasis
Minimum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Chukyo Hospital

UNKNOWN

Sponsor Role collaborator

Ebina General Hospital

UNKNOWN

Sponsor Role collaborator

Hitachi General Hospital

UNKNOWN

Sponsor Role collaborator

Kansai Medical University

OTHER

Sponsor Role collaborator

Kansai Medical University Medical Center

UNKNOWN

Sponsor Role collaborator

Nagasaki University

OTHER

Sponsor Role collaborator

Saga University

OTHER

Sponsor Role collaborator

University of the Ryukyus

OTHER

Sponsor Role collaborator

Wakayama Medical University

OTHER

Sponsor Role collaborator

Tajima Emergency and Critical Care Medical Center

UNKNOWN

Sponsor Role collaborator

Sapporo City General Hospital

UNKNOWN

Sponsor Role collaborator

Osaka General Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Jumpei Yoshimura, MD

Dr.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jumpei Yoshimura, MD

Role: PRINCIPAL_INVESTIGATOR

Osaka General Medical Center

Kazuma Yamakawa, MD, PhD

Role: STUDY_DIRECTOR

Osaka General Medical Center

Takeshi Morimoto, MD, PhD, MPH

Role: STUDY_DIRECTOR

Hyogo Medical University

Locations

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Chukyo Hospital

Nagoya, Aichi-ken, Japan

Site Status

Sapporo City General Hospital

Sapporo, Hokkaido, Japan

Site Status

Tajima Emergency and Critical Care Medical Center

Toyooka, Hyōgo, Japan

Site Status

Hitachi General Hospital

Hitachi, Ibaraki, Japan

Site Status

Ebina General Hospital

Ebina, Kanagawa, Japan

Site Status

University of the Ryukyus Hospital

Nishihara, Okinawa, Japan

Site Status

Kansai Medical University Hospital

Hirakata, Osaka, Japan

Site Status

Kansai Medical University Medical Center

Moriguchi, Osaka, Japan

Site Status

Nagasaki University Hospital

Nagasaki, , Japan

Site Status

Osaka General Medical Center

Osaka, , Japan

Site Status

Saga University Hospital

Saga, , Japan

Site Status

Wakayama Medical University Hospital

Wakayama, , Japan

Site Status

Countries

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Japan

References

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Yoshimura J, Yamakawa K, Ohta Y, Nakamura K, Hashimoto H, Kawada M, Takahashi H, Yamagiwa T, Kodate A, Miyamoto K, Fujimi S, Morimoto T. Effect of Gram Stain-Guided Initial Antibiotic Therapy on Clinical Response in Patients With Ventilator-Associated Pneumonia: The GRACE-VAP Randomized Clinical Trial. JAMA Netw Open. 2022 Apr 1;5(4):e226136. doi: 10.1001/jamanetworkopen.2022.6136.

Reference Type DERIVED
PMID: 35394515 (View on PubMed)

Yoshimura J, Yamakawa K, Kinoshita T, Ohta Y, Morimoto T. GRam stain-guided Antibiotics ChoicE for Ventilator-Associated Pneumonia (GRACE-VAP) trial: rationale and study protocol for a randomised controlled trial. Trials. 2018 Nov 8;19(1):614. doi: 10.1186/s13063-018-2971-2.

Reference Type DERIVED
PMID: 30409160 (View on PubMed)

Other Identifiers

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UMIN000031933

Identifier Type: REGISTRY

Identifier Source: secondary_id

29-C0707

Identifier Type: -

Identifier Source: org_study_id

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