NCT05176353

Ventilator-associated Pneumonia (VAP) Diagnostic Stewardship Trial

Completed NA Results posted Last updated 3 December 2024

What this trial tests

NA trial testing VAP diagnostic stewardship bundle in VAP - Ventilator Associated Pneumonia in 4,892 participants. Completed in 14 March 2023.

Timeline

11 February 2022

Primary endpoint
12 February 2023

14 March 2023

Quick facts

Lead sponsor	University of Michigan
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	health services research
Enrollment	4,892
Start date	11 February 2022
Primary completion	12 February 2023
Estimated completion	14 March 2023
Sites	1 location across United States

Drugs / interventions tested

• VAP diagnostic stewardship bundle

Conditions studied

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

Sponsor

University of Michigan

Who can join

Eligibility, any sex, with VAP - Ventilator Associated Pneumonia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Total Number of Deaths in the Pre vs Post-intervention Time Periods Among Study Participants Per 1000 Mechanically Ventilated Patient Days Primary · During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).

The number of deaths that occur across the entire study population will be divided by every 1000 days that the total number of patients were hospitalized in study ICUs, receiving mechanical ventilation. Data was collected retrospectively for 5 years prior to the intervention and for 1 year during the intervention period.

Group	Value	95% CI
Pre-VAP Diagnostic Stewardship	72	62 – 75
VAP Diagnostic Stewardship	73	64 – 82

Change in Ventilator-associated Events (V-A Events) (Using Centers for Disease Control/National Healthcare Safety Network Definitions) Per 1000 Patient Days Primary · During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).

The change in ventilator-associated events that occur across the entire study population will be divided by every 1000 days that the total number of patients were hospitalized in study ICUs, receiving mechanical ventilation, as shown by comparing pre-intervention data to post-intervention data. Data was collected retrospectively for 5 years prior to the intervention and for 1 year during the intervention period.

Group	Value	95% CI
Pre-VAP Diagnostic Stewardship	15	13 – 17
VAP Diagnostic Stewardship	10	7 – 14

Median Duration of Mechanical Ventilation Per Patient Primary · During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).

Group	Value	95% CI
Pre-VAP Diagnostic Stewardship	3	2 – 7
VAP Diagnostic Stewardship	3	2 – 7

Number of Positive Respiratory Cultures (RCs) Per 1,000 Mechanically-ventilated Patient Days (MVPDs) Secondary · During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).

Positive respiratory cultures were defined as any respiratory culture growing a bacterial organism, regardless of total colony-forming units/mL

Group	Value	95% CI
Pre-VAP Diagnostic Stewardship	127	122 – 131
VAP Diagnostic Stewardship	102	92 – 112

Total ICU Antibiotic Utilization Rates Secondary · During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).

Rates are shown as total antibiotic days of therapy per 1000 mechanically-ventilated patient days. A "Day of therapy" is defined as a calendar day in which a patient received a systemically-administered antibiotic, regardless of dose. Receipt of multiple, unique antibiotics on a given calendar day were counted cumulatively, that is, if a patient received 3 unique antibiotics that was counted as three days of therapy.

Group	Value	95% CI
Pre-VAP Diagnostic Stewardship	1361	1346 – 1376
VAP Diagnostic Stewardship	1335	1300 – 1372

Broad-spectrum ICU Antibiotic Utilization Rates Secondary · During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).

Utilization rates are shown as broad-spectrum antibiotic days of therapy per 1000 mechanically-ventilated patient days. Broad-spectrum antibiotics were defined as antibiotics with expected coverage against methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa. A "day of therapy" is defined as a calendar day in which a patient received a systemically-administered antibiotic, regardless of dose. Receipt of multiple, unique antibiotics on a given calendar day were counted cumulatively, that is, if a patient received 3 unique antibiotics that was counted as three days of therapy. .

Group	Value	95% CI
Pre-VAP Diagnostic Stewardship	1199	1177 – 1205
VAP Diagnostic Stewardship	1149	1116 – 1184

Number of Respiratory Cultures Ordered Per 1000 Mechanically-ventilated Patient Days Secondary · During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).

Group	Value	95% CI
Pre-VAP Diagnostic Stewardship	334	327 – 341
VAP Diagnostic Stewardship	268	252 – 285

Percentage of Respiratory Cultures Obtained by Bronchoalveolar Lavage (BAL) Secondary · During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).

Group	Value	95% CI
Pre-VAP Diagnostic Stewardship	53.1
VAP Diagnostic Stewardship	56.9

Percentage of Respiratory Cultures From BAL Samples With Alveolar Neutrophils <50% Following Study Intervention. Secondary · 6 months post-intervention

Group	Value	95% CI
VAP Diagnostic Stewardship	4.3

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 6 years (including 5 years pre-intervention and 1-year post intervention).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pre-VAP Diagnostic Stewardship

Serious: 278/4205 (7%)

Deaths: 1666/4205

VAP Diagnostic Stewardship

Serious: 34/687 (5%)

Deaths: 284/687

Serious adverse events (1 terms)

Reaction	System	Pre-VAP Diagnostic Steward…	VAP Diagnostic Stewardship
ventilator associated events	Respiratory, thoracic and mediastinal disorders	—	—

Most-reported serious reactions: ventilator associated events.

Data from ClinicalTrials.gov NCT05176353 adverse events section.

Sponsor's own description

This is a prospective pilot/feasibility trial of a bundled diagnostic stewardship intervention at the level of the microbiologic testing pathway in ventilator-associated pneumonia (VAP). The study utilized a pre/post design and was initially registered as a single-arm trial because the study intervention could only be applied prospectively to a single group (all patients hospitalized in study ICUs requiring ventilation during the trial intervention period). The study objectives are to safely and effectively reduce antibiotic overuse and its attendant hazards (adverse drug events, Clostridioides difficile diarrhea and generation of multidrug-resistant organisms) among mechanically-ventilated patients. Participating ICUs will have the following three modifications made in their respiratory culture workflows for mechanically-ventilated patients: 1) providers will be required to select a valid indication for respiratory culture performance (worsening ventilator requirements, purulent sputum production, and/or new radiographic infiltrate on chest imaging); 2) respiratory cultures will be preferentially obtained via bronchoscopic or nonbronchoscopic BAL (by respiratory therapists) rather than via endotracheal aspiration; and 3) BAL samples will be sent for cell count and differentials, and respiratory culture results will not be released for samples with \<50% neutrophils. The study will carefully monitor adherence to study interventions, ICU-specific antibiotic utilization rates, and important safety metrics including rates of mortality, ventilator-dependence and ventilator-associated events.

The trial hypotheses are:

* Implementation of a VAP diagnostic stewardship bundle will be successfully implemented without significant increases in mortality or ventilator-associated events.
* Implementation of a VAP diagnostic stewardship bundle will be associated with a reduction in ICU-specific antibiotic utilization rates

Publications & conference data

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

1. A quasi-experimental study of a bundled diagnostic stewardship intervention for ventilator-associated pneumonia.
   Albin OR, Troost JP, Saravolatz L, Thomas MP, et al · · 2024 · cited 11× · PMID 38163481 · DOI 10.1016/j.cmi.2023.12.023
2. Reductions in ventilator-associated events following implementation of a ventilator-associated pneumonia diagnostic stewardship intervention: A difference-in-difference study.
   Albin O, Garcia Z, Troost J, Weirauch A, et al · · 2026 · PMID 41404771 · DOI 10.1017/ice.2025.10376
3. P-428. Impact of Diagnostic Stewardship Interventions on Ventilator-Associated Event Rates
   · 2025
4. 90. The Diagnosis of Ventilator-associated pneumonia (DIVA) trial: Results of a Clinical Trial of a Bundled VAP Diagnostic Stewardship Intervention
   · 2023