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Completed

NCT Number: NCT03506113

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

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.

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Key information

Conditions

Ventilator Associated Pneumonia Cross Infection Disease Attributes Healthcare-Associated Pneumonia Iatrogenic Disease Infections Inflammation Lung Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Pneumonia Pneumonia, Ventilator-Associated Respiratory Tract Diseases Respiratory Tract Infections Sepsis Systemic Inflammatory Response Syndrome

Age range

15 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Chukyo Hospital, Nagoya, Aichi-ken, Japan

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Gram stain-guided antibiotic choice

Drug

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

Guidelines-based antibiotics choice

Drug

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

Primary outcomes

  1. Clinical cure of VAP

    Time frame: 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 outcomes

  1. Select of anti-pseudomonal agents as initial antibiotic therapies

    Time frame: on day 1

  2. Select of anti-MRSA agents as initial antibiotic therapies

    Time frame: on day 1

  3. Coverage of initial antibiotic therapies

    Time frame: 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.

  4. 28-day mortality

    Time frame: up to 28 days

  5. ICU-free days

    Time frame: up to 28 days

  6. Ventilator-free days

    Time frame: up to 28 days

  7. Duration of antibiotic therapies

    Time frame: up to 28 days

  8. Need of escalation or de-escalation of antibiotic therapies

    Time frame: up to 28 days

    The investigators evaluate whether antibiotic agents are changed during the treatments of VAP.

  9. Adverse events related to antibiotics

    Time frame: up to 7 days after the end of therapy

    renal impairment, thrombocytopenia, diarrhoea, Clostridium difficile infection, skin rash, and seizure

  10. Inflammation marker

    Time frame: up to 14 days

    Laboratory marker of inflammation (CRP, PCT) on 2, 4, 6, 8, and 14 days

  11. Organ failure control

    Time frame: 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).

  12. Renal function

    Time frame: up to 14 days

    The investigators evaluate whether participants are performed a renal replacement therapy.

Sponsors and collaborators

Lead sponsor

Osaka General Medical Center

Other

Collaborators

  • Chukyo Hospital
  • Ebina General Hospital
  • Hitachi General Hospital
  • Kansai Medical University
  • Nagasaki University
  • Saga University
  • Sapporo City General Hospital
  • Tajima Emergency and Critical Care Medical Center
  • University of the Ryukyus
  • Wakayama Medical University

Registry information

Important dates

Study start
2018
Primary completion
2020
Study completion
2020
First posted
Apr 23, 2018
Registry last updated
Sep 21, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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