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Duration of Antibiotic Treatment for Early VAP (DATE) Trial (DATE)

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ClinicalTrials.gov Identifier: NCT01994980
Recruitment Status : Suspended (Pending IRB continuing review approval.)
First Posted : November 26, 2013
Last Update Posted : April 3, 2019
Sponsor:
Information provided by (Responsible Party):
Fredric Pieracci, Denver Health and Hospital Authority

Tracking Information
First Submitted Date  ICMJE November 18, 2013
First Posted Date  ICMJE November 26, 2013
Last Update Posted Date April 3, 2019
Study Start Date  ICMJE December 2013
Estimated Primary Completion Date February 13, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 10, 2018)
Clinical Response [ Time Frame: Daily for 28 days ]
CPIS score
Original Primary Outcome Measures  ICMJE
 (submitted: November 21, 2013)
  • Clinical Response [ Time Frame: Daily for 28 days ]
    CPIS score
  • Microbiologic response [ Time Frame: 1 Day after last day of treatment ]
    BAP culture <10^3 cfu/mL
  • Biomarker response [ Time Frame: Daily for either 4 or 8 days, dependent upon treatment arm ]
    Procalcitonin
Change History Complete list of historical versions of study NCT01994980 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2018)
  • Biomarker response [ Time Frame: Daily for either 4 or 8 days, dependent upon treatment arm ]
    Procalcitonin
  • Microbiologic response [ Time Frame: 1 Day after last day of treatment ]
    BAP culture <10^3 cfu/mL
  • Infection with MDR pathogen [ Time Frame: 28 days ]
    The patient has growth of a multidrug resistant pathogen on culture
  • Recurrence [ Time Frame: 28 days ]
    The patient has another occurrence of VAP after treatment
  • Ventilator free days [ Time Frame: 28 days ]
    The number of day the patient does need mechanical ventilation
  • Mortality [ Time Frame: 28 days ]
    The patient has died
Original Secondary Outcome Measures  ICMJE
 (submitted: November 21, 2013)
  • Recurrence [ Time Frame: 28 days ]
  • Infection with MDR pathogen [ Time Frame: 28 days ]
  • Ventilator free days [ Time Frame: 28 days ]
  • Mortality [ Time Frame: 28 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Duration of Antibiotic Treatment for Early VAP (DATE) Trial
Official Title  ICMJE A Randomized Clinical Trial of 4 vs. 8 Days of Definitive Antibiotic Therapy for Early Ventilator-Associated Pneumonia in the Surgical Intensive Care Unit
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Early Ventilator Associated Pneumonia
Intervention  ICMJE Drug: 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.
Other Name: Antibiotic for 4 days
Study Arms  ICMJE
  • Active Comparator: Default 4 days antibiotic therapy
    Default 4 days antibiotic therapy
    Intervention: Drug: Default 4 days antibiotic therapy
  • No Intervention: Default 8 days antibiotic therapy
    Default 8 days antibiotic therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: November 21, 2013)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2020
Estimated Primary Completion Date February 13, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

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Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01994980
Other Study ID Numbers  ICMJE 13-0205
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fredric Pieracci, Denver Health and Hospital Authority
Study Sponsor  ICMJE Denver Health and Hospital Authority
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Fredric Pieracci, MD MPH Denver Health and Hospital
PRS Account Denver Health and Hospital Authority
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP