Diagnostic Stewardship for Ventilator Associated Pneumonia

Ventilator Associated Pneumonia Clinical Trial

Official title:

Diagnostic Stewardship for Ventilator Associated Pneumonia: A Pragmatic Cluster-randomized Crossover Trial of a Hybrid Order-review and Laboratory Reporting Intervention

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05989269
• Other study ID #: HP-00100090
• Status: Recruiting
• Phase: N/A
• Start date: August 21, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: September 2023
• Source: University of Maryland, Baltimore
• Contact: Michelle Newman, BSN
• Phone: 4107060933
• Email: mnewman[@]som.umaryland.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this pragmatic cluster-randomized crossover trial is to test if less unnecessary antibiotics are prescribed when the lab reports respiratory culture test results in a specific way for patients who have respiratory cultures obtained, but do not meet clinical criteria for ventilator associated pneumonia (VAP). The main question it aims to answer is: Does a modified culture reporting intervention reduce unnecessary antibiotics for ventilated patients in the intensive care unit (ICU)? Researchers will compare antibiotic use outcomes between eligible patients whose test results are communicated using the modified reporting and those with standard reporting of results.

Description:

The specific aims of this project are:

Specific Aim 1: In a cluster-randomized crossover trial among 6 ICUs across 3 medical centers, evaluate the impact of a VAP diagnostic stewardship intervention on antibiotic use, VAP diagnoses, and adverse events.

Hypothesis: A change in unnecessary antibiotics for VAP and in VAP clinical diagnoses in the intervention vs. control periods across all sites, without a change in adverse events, is expected.

Specific Aim 2: Evaluate overall impact of intervention including clinical and antibiotic outcomes using the "Desirability of Outcome Ranking (DOOR)/ Response Adjusted for Duration of Antibiotic Risk (RADAR)" methodology.

Hypothesis: A change in overall patient outcomes (better DOOR ranking, accounting for duration of antibiotic use) in the intervention vs. control period is expected.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: December 31, 2024
• Est. primary completion date: September 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient located on ICU unit included in the study

• Patient is mechanically ventilated

• Patient had respiratory culture sent >48 hours after admission

• Patient age = 18 years

Exclusion Criteria:

• Extra corporeal membrane oxygenation (ECMO) at time of respiratory culture

• Heart or lung transplant

• Culture rejected by lab per standard lab protocol

• Prisoners

• Severe immunosuppression as defined by:

• <6 months from solid organ transplant (SOT) OR <6 months from treatment for acute rejection following SOT

• Active treatment for lymphoreticular malignancies

• Neutropenic < 1000

• Receiving lymphodepleting chemotherapy

• Allogeneic stem cell transplants <6 months

• Autologous stem cell transplants or chimeric antigen receptor T-cell (CAR-T) therapy <6 months out

• Allogeneic stem cell transplant with graft vs host disease (GVHD) or receiving 2 or more immunosuppressants

• Advanced or untreated human immunodeficiency virus (HIV) infection with CD4 < 200

• Receiving biologics within 6 months

Related Conditions & MeSH terms

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

Intervention

Other:
• Modified lab reporting
If appropriateness of culturing i.e., clinical criteria for pneumonia testing does not meet the algorithm AND there is growth of one or more organism(s) that are not considered normal upper respiratory flora, during the intervention period, the result will be modified to reflect the likelihood of asymptomatic colonization.

Locations

Country	Name	City	State
United States	University of Maryland	Baltimore	Maryland
United States	Baylor College of Medicine	Houston	Texas
United States	Virginia Commonwealth University	Richmond	Virginia

Sponsors (5)

Lead Sponsor	Collaborator
University of Maryland, Baltimore	Baylor College of Medicine, Centers for Disease Control and Prevention, George Washington University, Virginia Commonwealth University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Desirability of Outcome Ranking (DOOR)/Response Adjusted for Duration of Antibiotic Risk (RADAR)	The clinical outcome of a participant will be ranked from most to least desirable outcome, to obtain a 5-level ordinal outcome. We will conduct a series of pairwise comparisons of each intervention patient to each control patient using two rules: When comparing patients with different overall clinical outcomes, the patient with a better overall clinical outcome based on pre-specified ordered ranks is determined to have the better outcome. When comparing two patients who have the same rank based on overall clinical outcome, the patient with a shorter course of antibiotics has the better outcome. The DOOR/RADAR probability represents the probability that a randomly selected participant who received the intervention (modified reporting) has a better overall outcome than a randomly selected participant who received standard reporting (control), accounting for antibiotic duration of therapy.	Measured within the 28 days after the index respiratory culture
Primary	Proportion of unnecessary antibiotic therapy	The primary efficacy outcome is change in proportion of unnecessary antibiotic therapy for presumed VAP in the intervention (modified reporting) period compared to control (standard reporting) period.; Antibiotic use for VAP relative to the index respiratory culture will be classified as follows: Not on empiric antibiotic(s), new antibiotic started based on index respiratory culture result; Not on empiric antibiotic(s), no new antibiotics initiated based on culture result; On empiric antibiotic(s), changed based on index respiratory culture, completed course for VAP; On empiric antibiotic(s), continued without change following index respiratory culture, completed course for VAP; On empiric antibiotic(s), antibiotics discontinued based on culture results; On empiric antibiotics(s), but this was not directed towards VAP Antibiotic use in categories a, c, and d will together be considered "unnecessary antibiotic therapy for VAP treatment".	Respiratory culture collection date through day 28 or patient discharge
Secondary	Antibiotic consumption	To understand the impact on antibiotic use in ICU patients, we will measure the duration of antibiotic therapy for study patients, unit-level total antibiotic days of therapy (DOTs) standardized to patient census, and unit-level respiratory antibiotic days of therapy (DOTs) standardized to patient census.	Measured over the 6 month control period and the 6 month intervention period
Secondary	Frequency of clinical diagnosis of VAP and tracheobronchitis	Measurement of this outcome will help understand how modification of reporting would influence the likelihood of a patient receiving a diagnosis of VAP. The clinical diagnosis of VAP is an intermediate outcome that precedes the endpoint of antibiotic use. Because there are no consensus definitions for VAP, we will use the treating clinician's documentation of pneumonia or VAP and treatment for those conditions to capture this outcome. Similarly, clinical diagnosis of tracheobronchitis within 7 days after the index culture will also be recorded.	Measured within the 7 days after the index respiratory culture
Secondary	Antibiotic use outcome sensitivity analysis	We will perform a sensitivity analysis of the impact on antibiotic use outcomes after excluding patients diagnosed with tracheobronchitis within 7 days of index culture. The hypothesis is that the intervention will have limited impact on those diagnosed and treated for tracheobronchitis, and thus, we may see a larger difference between intervention and control when excluding patients with diagnoses of tracheobronchitis.	Measured within the 7 days after the index respiratory culture
Secondary	Number of Ventilator-free days	Ventilator-free days is defined as the number of calendar days within 28 days after the index respiratory culture on which the patient was not mechanically ventilated. Any patient dying within 28 days of the index respiratory culture collection will be assigned zero ventilator-free days. Ventilator-free days will be compared between the intervention and control periods for all study ICUs combined, and by hospital.	Measured within the 28 days after the index respiratory culture
Secondary	Frequency of provider requests for complete reports	Frequency of requests for complete reports in the intervention period - these data are applicable in the intervention period only. This will be a primarily descriptive analysis to help us understand if the intervention worked as intended i.e., how frequently did clinicians still want the full report with organism identification despite the nudge to consider asymptomatic colonization.	Measured during the 6 month intervention period
Secondary	Incidence of Adverse Events	Death, bacteremia, and septic shock (from any cause) within 7 days of the index culture order will be recorded as potential significant adverse events from a delayed or missed true VAP diagnosis or delay in initiation of appropriate antimicrobial therapy. Two-person adjudication will be used to determine whether the above events were attributed to the intervention, during the intervention period. Rates of these events will be compared between intervention and control periods individually for each event, and as a combined adverse event outcome.	Measured within the 7 days after the index respiratory culture