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

Ventilator Associated Pneumonia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03506113
• Other study ID #: 29-C0707
• Secondary ID: UMIN000031933
• Status: Completed
• Phase: Phase 4
• Start date: April 1, 2018
• Est. completion date: June 28, 2020

Study information

• Verified date: September 2022
• Source: Osaka General Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 206
• Est. completion date: June 28, 2020
• Est. primary completion date: June 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Ventilator-Associated
• Ventilator Associated Pneumonia

Intervention

Drug:
• Gram stain-guided antibiotic choice
The results of Gram staining of endotracheal aspirate are used to guide the selection of antibiotics.
• Guidelines-based antibiotics choice
Patients are administered the combination of an anti-pseudomonal agent and anti-MRSA agent according to IDSA/ATS guidelines

Locations

Country	Name	City	State
Japan	Ebina General Hospital	Ebina	Kanagawa
Japan	Kansai Medical University Hospital	Hirakata	Osaka
Japan	Hitachi General Hospital	Hitachi	Ibaraki
Japan	Kansai Medical University Medical Center	Moriguchi	Osaka
Japan	Nagasaki University Hospital	Nagasaki
Japan	Chukyo Hospital	Nagoya	Aichi
Japan	University of the Ryukyus Hospital	Nishihara	Okinawa
Japan	Osaka General Medical Center	Osaka
Japan	Saga University Hospital	Saga
Japan	Sapporo City General Hospital	Sapporo	Hokkaido
Japan	Tajima Emergency and Critical Care Medical Center	Toyooka	Hyogo
Japan	Wakayama Medical University Hospital	Wakayama

Sponsors (12)

Lead Sponsor	Collaborator
Osaka General Medical Center	Chukyo Hospital, Ebina General Hospital, Hitachi General Hospital, Kansai Medical University, Kansai Medical University Medical Center, Nagasaki University, Saga University, Sapporo City General Hospital, Tajima Emergency and Critical Care Medical Center, University of the Ryukyus, Wakayama Medical University

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical cure of VAP	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.	up to 22 days
Secondary	Select of anti-pseudomonal agents as initial antibiotic therapies		on day 1
Secondary	Select of anti-MRSA agents as initial antibiotic therapies		on day 1
Secondary	Coverage of initial antibiotic therapies	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.	on day 1
Secondary	28-day mortality		up to 28 days
Secondary	ICU-free days		up to 28 days
Secondary	Ventilator-free days		up to 28 days
Secondary	Duration of antibiotic therapies		up to 28 days
Secondary	Need of escalation or de-escalation of antibiotic therapies	The investigators evaluate whether antibiotic agents are changed during the treatments of VAP.	up to 28 days
Secondary	Adverse events related to antibiotics	renal impairment, thrombocytopenia, diarrhoea, Clostridium difficile infection, skin rash, and seizure	up to 7 days after the end of therapy
Secondary	Inflammation marker	Laboratory marker of inflammation (CRP, PCT) on 2, 4, 6, 8, and 14 days	up to 14 days
Secondary	Organ failure control	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).	up to 14 days
Secondary	Renal function	The investigators evaluate whether participants are performed a renal replacement therapy.	up to 14 days