Duration of Antibiotic Treatment for Early VAP (DATE) Trial

NCT ID: NCT01994980

Last Updated: 2023-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2021-11-05

Brief Summary

Hypothesis: 4 days of antibiotic therapy, as compared to 8 days, is equally effective and results in decreased antibiotic exposure among surgical ICU patients with early VAP.

Detailed Description

The prevalence of multi-drug resistant (MDR) pathogens in intensive care units (ICUs) worldwide has reached epidemic proportions. In some cases, the choice of potential therapy is limited or even non-existent. Antibiotic prescription, through selection pressure, represents the main mechanism by which resistance emerges. Limitations in the development of new antibiotics underscores the importance of adherence to the principles of antibiotic stewardship.

Ventilator associated pneumonia (VAP) is the most common serious infection in mechanically ventilated, critically ill patients. Approximately one half of antibiotic prescription in the ICU is related to VAP, including prophylactic, empiric, and definitive therapy. The development of evidence-based algorithms for the rational use of antibiotics in the management of patients with both suspected and confirmed VAP is pivotal to decreasing the emergence of MDR pathogens.

Shortening the duration of antimicrobial therapy for VAP represents one strategy to curtail the emergence of MDR pathogens. Although current guidelines recommend a treatment course of 8-14 days, both clinical and microbiologic resolution (MR) of infection typically occur much sooner [10, 11]. In one study of ICU patients ventilated for > 5 days who developed VAP, 8 days of antimicrobial therapy was equally as effective as 14 days, provided VAP was not caused by a non-lactose fermenting gram negative bacillus. Favorable results following shorter courses of therapy for VAP have been observed, albeit in small, uncontrolled series.

One subset of patients for whom a decreased duration of antimicrobial therapy may be particularly effective is those who develop VAP ≤ 5 days after intubation (early VAP). Early VAP comprises approximately one half of cases of pneumonia diagnosed in the ICU. Furthermore, as compared to patients who develop late VAP, patients who develop early VAP are more likely to be infected with community-acquired pathogens sensitive to narrow spectrum antibiotics. Finally, nearly all cases of early VAP caused by sensitive pathogens demonstrate MR after relatively short (3-5 days) courses of therapy.

Conditions

Early Ventilator Associated Pneumonia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Default 4 days antibiotic therapy

Default 4 days antibiotic therapy

Group Type: ACTIVE_COMPARATOR

Default 4 days antibiotic therapy

Intervention Type: DRUG

The intervention for this trial involves a shorter duration of antibiotic therapy. Specifically, a default of 4 vs. 8 days.

Default 8 days antibiotic therapy

Default 8 days antibiotic therapy

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Default 4 days antibiotic therapy

The intervention for this trial involves a shorter duration of antibiotic therapy. Specifically, a default of 4 vs. 8 days.

Intervention Type: DRUG

Other Intervention Names

Antibiotic for 4 days

Eligibility Criteria

Inclusion Criteria

1. Surgical patient

2. VAP, defined as clinical suspicion plus a bronchoalveolar lavage (BAL) culture showing ≥105 cfu/mL of at least one pathogen. The quantitative microbiology threshold will be lowered to ≥104 cfu/mL if the patient was being treated with antibiotics to which the pathogen is sensitive at the time of the BAL. Clinical suspicion of VAP is defined as at least one point for ≥ 2 variables in the Clinical Pulmonary Infection Score (CPIS, described below).

3. Ventilated ≤ 5 days at the time that the BAL was obtained.

4. Hospital LOS ≤ 5 days at the time that the BAL was obtained.

Exclusion Criteria

1. Age < 18 years.

2. Prior episode of VAP for the index admission (the patient may have had prior BALs sent for culture, but these cannot have met the above mentioned diagnostic criteria for VAP).

3. VAP caused by a MDR pathogen: Early VAP is rarely caused by a MDR pathogen; in a recent analysis of our surgical ICU, 94% of cases of early VAP were caused by a highly sensitive pathogen (MSSA 39%, H flu 35%, S. pneumo 16%, E. coli 9%) (Pieracci in press). Patients with early VAP caused by the following MDR pathogens will be excluded: Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-intermediate Staphylococcus aureus (VISA), pseudomonas aeruginosa, Vancomycin-resistant enterococcus (VRE), Acinetobacter baumannii, Stenotrophomonas maltophilia, and extended-spectrum beta lactamase producing gram negative bacilli.

4. Antibiotic therapy for ≥ 5 of the last 10 days preceding the BAL.

5. Septic shock, defined as evidence of tissue hypoperfusion after adequate volume expansion, due to infection, and requiring ≥ 1 vasopressor.

6. Current or recent (within 30 days) use of immunosuppressive medications.

7. Length of stay ≥ 48 hours in a transferring facility.

8. Inpatient hospitalization within 30 days of admission.

9. Pregnancy or lactation.

10. Legal arrest or incarceration.

11. Moribund state in which death is imminent.

-

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Denver Health and Hospital Authority

OTHER

Sponsor Role: lead

Responsible Party

Fredric Pieracci

Assistant Professor of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fredric Pieracci, MD MPH

Role: PRINCIPAL_INVESTIGATOR

Denver Health and Hospital

Locations

Denver Health Medical Center

Denver, Colorado, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

13-0205

Identifier Type: -

Identifier Source: org_study_id