Shortened Antibiotic Therapy for Ventilator-Associated Pneumonia

(DATE Trial)

Overseen By Jonathan Meizoso, MD, MSPH

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Miami

Must not be taking: Immunosuppressives

Disqualifiers: Age < 18, Pregnancy, Septic shock, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4-7 days

24 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to see if the amount of antibiotics given for ventilator-associated pneumonia (VAP) can be decreased in order to reduce the risk of adverse effects associated with antibiotics, while at the same time ensuring the participant's safety.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive medications or have been on antibiotics for more than 5 of the last 10 days, you may not be eligible to participate.

What data supports the effectiveness of the treatment for ventilator-associated pneumonia?

Research suggests that a shorter course of antibiotic therapy (7-8 days) is effective for most patients with ventilator-associated pneumonia and does not increase the risk of death. Additionally, using broad-spectrum antibiotics initially and then focusing treatment based on specific test results can improve outcomes and reduce the chance of resistance. ^{1 2 3 4 5}

Is shortened antibiotic therapy for ventilator-associated pneumonia safe for humans?

Research suggests that a shorter duration of antibiotic therapy (7-8 days) for ventilator-associated pneumonia is generally safe and does not increase the risk of death. ^{4 5 6 7 8}

How is the Standard of Care Antibiotic Therapy for ventilator-associated pneumonia different from other treatments?

The Standard of Care Antibiotic Therapy for ventilator-associated pneumonia is unique because it involves a shorter duration of treatment, typically 7-8 days, which is considered adequate for most patients and helps reduce the risk of developing antibiotic resistance without increasing mortality. ^{1 4 5 9 10}

Research Team

Jonathan Meizoso, MD, MSPH

Principal Investigator

University of Miami

Eligibility Criteria

This trial is for surgical patients with early ventilator-associated pneumonia (VAP) that occurred within 2-7 days of intubation, who haven't been in the hospital for more than 10 days at VAP diagnosis. Participants must be able to consent or have a representative do so. Excluded are those with septic shock, recent immunosuppressant use, legal incarceration, prior VAP this admission, certain resistant infections, extensive recent antibiotics use, imminent death prognosis, transfer from another facility after 72 hours+, and pregnant or breastfeeding women.

Inclusion Criteria

I am scheduled for or have had surgery.

I developed a lung infection within 2-7 days after being put on a breathing machine.

I or my legal representative can give consent for my participation.

Exclusion Criteria

I was hospitalized for more than 72 hours before being transferred.

I've been on antibiotics for more than 5 days recently.

I have septic shock and need more than one medication to maintain my blood pressure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 4 or 7 days of antibiotic therapy for early ventilator-associated pneumonia (VAP)

4-7 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of VAP recurrence and clinical improvement

Up to 30 days

Long-term Follow-up

Participants are monitored for hospital length of stay and in-hospital mortality

Up to 1 year

Treatment Details

Interventions

• Standard of Care Antibiotic Therapy

Trial Overview The study tests if shorter antibiotic treatment (4 days) is as safe and effective as the standard duration (7 days) for early ventilator-associated pneumonia. The goal is to minimize antibiotic-related side effects without compromising patient safety.

Participant Groups

Group I: 4 Days of Antibiotics Group Experimental Treatment 1 Intervention

Participants will receive 4 days of antibiotic therapy administered as per the standard of care for the treatment of early ventilator associated pneumonia (VAP).

Group II: 7 Days of Antibiotics Group Active Control 1 Intervention

Participants will receive 7 days of antibiotic therapy administered as per the standard of care for the treatment of early ventilator associated pneumonia (VAP).

Standard of Care Antibiotic Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Standard Antibiotic Therapy for:

• Ventilator-associated pneumonia (VAP)
• Bacterial infections
• Respiratory tract infections

Approved in United States as Standard Antibiotic Therapy for:

• Ventilator-associated pneumonia (VAP)
• Bacterial infections
• Respiratory tract infections

Approved in Canada as Standard Antibiotic Therapy for:

• Ventilator-associated pneumonia (VAP)
• Bacterial infections
• Respiratory tract infections

Approved in Japan as Standard Antibiotic Therapy for:

• Ventilator-associated pneumonia (VAP)
• Bacterial infections
• Respiratory tract infections

Approved in China as Standard Antibiotic Therapy for:

• Ventilator-associated pneumonia (VAP)
• Bacterial infections
• Respiratory tract infections

Approved in Switzerland as Standard Antibiotic Therapy for:

• Ventilator-associated pneumonia (VAP)
• Bacterial infections
• Respiratory tract infections

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Findings from Research

A review of nine trials indicates that short courses of antimicrobial treatment (≤10 days) for ventilator-associated pneumonia are as effective as longer courses (14-21 days) without negatively impacting patient outcomes such as mortality or ICU stay.

The evidence supports using short-course therapy for patients with ventilator-acquired pneumonia, particularly when the infection is not caused by nonfermenting Gram-negative bacilli, potentially leading to reduced antibiotic exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal duration of the antimicrobial treatment of ventilator-acquired pneumonia. Grammatikos, AP., Siempos, II., Michalopoulos, A., et al.[2008]

Ventilator-associated pneumonia is a serious condition that can lead to high rates of illness and death in critically ill patients, highlighting the need for effective treatment strategies.

Using an initial aggressive approach with broad-spectrum antibiotics tailored to local pathogen distribution and patient risk factors can improve outcomes by reducing the likelihood of inappropriate therapy and antibiotic resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy for ventilator-associated pneumonia: what works, what doesn't. Hijazi, M., Al-Ansari, M.[2005]

Antibiotic treatment for ventilator-associated pneumonia (VAP) diagnosed using invasive methods (like bronchoscopic protected specimen brush) improves survival compared to withholding treatment, while treatment based on clinical criteria may actually lower survival rates.

The study suggests that using invasive or semi-invasive diagnostic techniques is crucial for accurately diagnosing VAP and guiding effective therapy, as the mortality rate for untreated VAP can be significantly high, approaching 70%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and treatment of ventilator-associated pneumonia--impact on survival. A decision analysis. Sterling, TR., Ho, EJ., Brehm, WT., et al.[2019]

In a study of 156 critically ill patients with suspected ventilator-associated pneumonia (VAP), those treated with antipseudomonal penicillins plus beta-lactamase inhibitors had significantly lower in-hospital mortality rates, suggesting these antibiotics are effective for initial empiric therapy.

The study found no significant difference in outcomes between monotherapy and combination therapy, indicating that the choice of antibiotic regimen may not impact length of hospital stay or days free of antibiotics, but appropriate initial treatment is crucial for improving survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variability in antibiotic prescribing patterns and outcomes in patients with clinically suspected ventilator-associated pneumonia. Fowler, RA., Flavin, KE., Barr, J., et al.[2022]

Recent studies suggest that a shorter duration of antibiotic therapy (7-8 days) is effective for treating ventilator-associated pneumonia without increasing mortality rates, challenging the traditional 2-week treatment standard.

There is a need for further research to definitively establish the minimum effective duration of antibiotic therapy for this condition, especially in the context of rising multi-drug-resistant infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ventilator-associated pneumonia: gearing towards shorter-course therapy. Chua, Tde J., File, TM.[2006]

Shorter antibiotic regimens for treating ventilator-associated pneumonia (VAP) lead to significantly more antibiotic-free days without negatively affecting patient mortality, based on recent randomized controlled trials.

While shorter treatments reduce the emergence of multidrug-resistant pathogens, they may result in higher relapse rates for infections caused by nonfermenting Gram-negative bacilli, highlighting the need for a comprehensive treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duration of therapy of ventilator-associated pneumonia. Dimopoulos, G., Matthaiou, DK.[2016]

In a study of 111 ICU patients with ventilator-associated pneumonia (VAP), appropriate initial antibiotic therapy significantly reduced the length of ICU stay for survivors, averaging 12 days compared to 20 days for those with inappropriate therapy.

While not statistically significant, there was a trend towards lower hospital mortality in patients receiving appropriate initial antibiotics (47.3% vs 60.7%), suggesting that timely and effective antibiotic treatment may improve outcomes in VAP cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of appropriateness of initial antibiotic therapy on the outcome of ventilator-associated pneumonia. Dupont, H., Mentec, H., Sollet, JP., et al.[2022]

This systematic review analyzed 12 studies with 3571 participants and found no significant difference in all-cause mortality or clinical cure rates between monotherapy and combination therapy for treating ventilator-associated pneumonia (VAP), suggesting that effective monotherapy can be safely used.

Carbapenem antibiotics showed a statistically significant increase in clinical cure rates compared to non-carbapenem therapies, indicating that carbapenems may be a more effective option for treating VAP, although the overall quality of evidence was moderate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotics for ventilator-associated pneumonia. Arthur, LE., Kizor, RS., Selim, AG., et al.[2023]

Ventilator-associated pneumonia is a major cause of infections in intensive care units, leading to significant antibiotic use; invasive diagnostic methods can help accurately identify bacterial pneumonia and optimize antibiotic treatment.

An 8-day antibiotic regimen is suggested as a standard treatment for ventilator-associated pneumonia, but exceptions exist for certain high-risk patients, emphasizing the need to avoid unnecessary prolonged antibiotic use to prevent the development of multidrug-resistant bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of quantitative cultures and reduced duration of antibiotic regimens for patients with ventilator-associated pneumonia to decrease resistance in the intensive care unit. Chastre, J., Luyt, CE., Combes, A., et al.[2007]

The REGARD-VAP trial is investigating whether a shorter course of antibiotics can effectively treat ventilator-associated pneumonia (VAP) without increasing the risk of death or pneumonia recurrence, involving 460 patients across ICUs in Nepal, Thailand, and Singapore.

Participants in the short-course treatment group may stop antibiotics as early as day 3 if cultures are negative, compared to at least 8 days for standard care, aiming to reduce antibiotic exposure while maintaining safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reducing antibiotic treatment duration for ventilator-associated pneumonia (REGARD-VAP): a trial protocol for a randomised clinical trial. Mo, Y., West, TE., MacLaren, G., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Optimal duration of the antimicrobial treatment of ventilator-acquired pneumonia. [2008]

2. United States pubmed.ncbi.nlm.nih.gov

Therapy for ventilator-associated pneumonia: what works, what doesn't. [2005]

3. United States pubmed.ncbi.nlm.nih.gov

Diagnosis and treatment of ventilator-associated pneumonia--impact on survival. A decision analysis. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Variability in antibiotic prescribing patterns and outcomes in patients with clinically suspected ventilator-associated pneumonia. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Ventilator-associated pneumonia: gearing towards shorter-course therapy. [2006]

6. United States pubmed.ncbi.nlm.nih.gov

Duration of therapy of ventilator-associated pneumonia. [2016]

7. United States pubmed.ncbi.nlm.nih.gov

Impact of appropriateness of initial antibiotic therapy on the outcome of ventilator-associated pneumonia. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Antibiotics for ventilator-associated pneumonia. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Use of quantitative cultures and reduced duration of antibiotic regimens for patients with ventilator-associated pneumonia to decrease resistance in the intensive care unit. [2007]

10. England pubmed.ncbi.nlm.nih.gov

Reducing antibiotic treatment duration for ventilator-associated pneumonia (REGARD-VAP): a trial protocol for a randomised clinical trial. [2021]