Early Ventilator Associated PneumoniaDATENCT01994980
Duration of Antibiotic Treatment for Early VAP (DATE) Trial
A study testing Default 4 days antibiotic therapy in people with Early Ventilator Associated Pneumonia, run by Denver Health and Hospital Authority at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Early Ventilator Associated Pneumonia
- What is being tested?
- Default 4 days antibiotic therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2013to 5 Nov 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Surgical patient
- 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).
- Ventilated ≤ 5 days at the time that the BAL was obtained.
- Hospital LOS ≤ 5 days at the time that the BAL was obtained.
Who cannot join
- Age < 18 years.
- 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).
- 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.
- Antibiotic therapy for ≥ 5 of the last 10 days preceding the BAL.
- Septic shock, defined as evidence of tissue hypoperfusion after adequate volume expansion, due to infection, and requiring ≥ 1 vasopressor.
- Current or recent (within 30 days) use of immunosuppressive medications.
Show all 12Show fewer
- Length of stay ≥ 48 hours in a transferring facility.
- Inpatient hospitalization within 30 days of admission.
- Pregnancy or lactation.
- Legal arrest or incarceration.
- Moribund state in which death is imminent.
- -
Trial locations and contacts
1 site in 1 country.
United States1 site
Denver Health Medical Center
Denver, Colorado, 80204
About this study
Official title: A Randomized Clinical Trial of 4 vs. 8 Days of Definitive Antibiotic Therapy for Early Ventilator-Associated Pneumonia in the Surgical Intensive Care Unit
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.
Read the 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
- Being tested
- Default 4 days antibiotic therapy
- Medical subject headings
- Pneumonia, Ventilator-Associated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Default 4 days antibiotic therapyDrug
Also called Antibiotic for 4 days
The intervention for this trial involves a shorter duration of antibiotic therapy. Specifically, a default of 4 vs. 8 days.
| Study group | Role | What they receive |
|---|---|---|
| Default 4 days antibiotic therapy | Active comparator | Default 4 days antibiotic therapy Receives: Drug: Default 4 days antibiotic therapy |
| Default 8 days antibiotic therapy | No intervention | Default 8 days antibiotic therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Response
Clinical Pulmonary Infection Score (CPIS) score. Scales of this score include Temperature, Blood Leukocytes, Tracheal Secretions, Oxygenation, Pulmonary Radiography, and Culture of Tracheal Aspirate. Each scale can have sub-scores ranging from 0-2, with a total CPIS score ranging from 0-12. In this outcome measure, higher scores mean worse functioning and risk for worse outcomes. Scores for the patients analyzed on this outcome measure were taken daily for 28 days and then averaged across that time point.
Measured: Daily for 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2013 (estimated)
- Study startDec 2013
- Primary completion5 Nov 2021
- Study completion5 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Early Ventilator Associated PneumoniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Denver Health and Hospital Authority
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fredric Pieracci, Denver Health and Hospital Authority
- Investigators
- Fredric Pieracci, MD MPH, Principal investigator, Denver Health and Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01994980
- Sponsor's protocol ID
- 13-0205
- Acronym
- DATE
- Status last verified
- Dec 2022
- First submitted
- 18 Nov 2013
- Last updated
- 10 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Clinical Trial of 4 vs. 8 Days of Definitive Antibiotic Therapy for Early Ventilator-Associated Pneumonia in the Surgical Intensive Care Unit
- ClinicalTrials.gov ID
- NCT01994980
- Acronym / sponsor ID
- DATE / 13-0205
- Conditions
- Early Ventilator Associated Pneumonia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Denver Health and Hospital AuthorityUniversity, hospital or other
- Study start
- Dec 2013
- Primary completion
- 5 Nov 2021 (actual)
- Study completion
- 5 Nov 2021 (actual)
- First posted
- 26 Nov 2013 (estimated)
- Results
- Posted 10 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Default 4 days antibiotic therapy | Active comparator | Drug: Default 4 days antibiotic therapyDefault 4 days antibiotic therapy |
| Default 8 days antibiotic therapy | No intervention | –Default 8 days antibiotic therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Surgical patient
- 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).
- Ventilated ≤ 5 days at the time that the BAL was obtained.
- Hospital LOS ≤ 5 days at the time that the BAL was obtained.
Key exclusion criteria (12 listed)
- Age < 18 years.
- 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).
- 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.
- Antibiotic therapy for ≥ 5 of the last 10 days preceding the BAL.
- Septic shock, defined as evidence of tissue hypoperfusion after adequate volume expansion, due to infection, and requiring ≥ 1 vasopressor.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Default 4 days antibiotic therapyAlso: Antibiotic for 4 daysThe intervention for this trial involves a shorter duration of antibiotic therapy. Specifically, a default of 4 vs. 8 days. | Drug | Default 4 days antibiotic therapy |
Primary outcome
Clinical Response
Time frame: Daily for 28 days
Clinical Pulmonary Infection Score (CPIS) score. Scales of this score include Temperature, Blood Leukocytes, Tracheal Secretions, Oxygenation, Pulmonary Radiography, and Culture of Tracheal Aspirate. Each scale can have sub-scores ranging from 0-2, with a total CPIS score ranging from 0-12. In this outcome measure, higher scores mean worse functioning and risk for worse outcomes. Scores for the patients analyzed on this outcome measure were taken daily for 28 days and then averaged across that time point.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Early Ventilator Associated Pneumonia
Not yet recruitingObservational study
Early Identification of Pathogens in Children With Respiratory Tract Infection by Mechanical Ventilation Using mNGS
VAP - Ventilator Associated Pneumonia
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EaRly impAct theraPy With Ceftazidime-avibactam Via rapID Diagnostics
Blood Stream Infections, Ventilator Associated Pneumonia
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Combined Use of a Respiratory Multiplex PCR and Algorithm-based Therapy to Improve Early Optimization of Antibiotic Therapy in Critically Ill Patients With Ventilator-associated Pneumonia
Ventilator Associated Pneumonia ( VAP)
Not yet recruiting
EARLY Antibiotics aDAptation in Severe Pneumonia(The EARLY ADAPT Study)
VAP - Ventilator Associated Pneumonia, Antibiotic
Not yet recruitingObservational study
PK/PD Target Attainment of Ceftriaxone for the Prevention of Early Ventilator-associated Pneumonia in Neurologically Injured Patients
Early Ventilator Associated Pneumonia, Acute Brain Injuries
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fredric Pieracci, MD MPH principal investigator
Denver Health and Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Default 4 days antibiotic therapy in people with Early Ventilator Associated Pneumonia, run by Denver Health and Hospital Authority at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Response (time frame: Daily for 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2023.