PneumoniaPhase 4NCT05102162
BL Infusion Trial:Beta-lactam Continuous Versus Intermittent Infusion and Associated Bacterial Resistance and Therapy Outcomes in Critically Ill Patients With Severe Pneumonia
A Phase 4 study testing Cefepime, Meropenem, or Piperacillin/Tazobactam in people with Pneumonia, run by University of Florida at 1 site in United States.
Trial summary
The study plans to randomize a total of 240 patients infected with Gram-negative bacterial pneumonia to receive beta-lactam (meropenem, cefepime, or piperacillin/tazobactam) continuous or intermittent infusion and collect baseline and regular follow-up respiratory cultures to assess the development of new resistance. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Pneumonia
- What is being tested?
- Cefepime, Meropenem, or Piperacillin/Tazobactam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Dec 2021to 28 Feb 2023
- Phase
- Phase 4
- 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Admission to the ICU with severe pneumonia (IDSA/ATS 2016/2019): presence of signs, symptoms and confirmatory chest imaging consistent with pneumonia (e.g. fever, cough and pulmonary infiltrate by chest radiograph)
- Age ≥18 years
- Positive respiratory culture (with or without an initial positive rapid identification test and/or Gram stain) for Gram-negative bacteria including, but not limited to, P. aeruginosa, K. pneumoniae, E. coli, S. marcescens, H. influenzae, Enterobacter spp., M. catarrhalis, A. baumannii, Achromobacter spp., P. mirabilis, and/or B. cepacia
- Received within the last 72 hours or will receive meropenem, cefepime, or piperacillin/tazobactam therapy
Who cannot join
- Pregnancy
- Prisoners
- Allergy to the beta-lactams to be administered in this study
- On renal replacement therapy at the time of randomization
- Baseline culture resistant to the beta-lactams in the study
- COVID patients enrolled in other trials
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Beta-lactam Continuous Versus Intermittent Infusion and Associated Bacterial Resistance and Therapy Outcomes in Critically Ill Patients With Severe Pneumonia
The study plans to randomize a total of 240 patients infected with Gram-negative bacterial pneumonia to receive beta-lactam (meropenem, cefepime, or piperacillin/tazobactam) continuous or intermittent infusion and collect baseline and regular follow-up respiratory cultures to assess the development of new resistance. The investigators will measure beta-lactam concentration to assess the impact of drug exposure on the bacterial resistance.
- Conditions
- Pneumonia
- Being tested
- Cefepime, Meropenem, or Piperacillin/Tazobactam
- Medical subject headings
- Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cefepime, Meropenem, or Piperacillin/TazobactamDrug
Also called Maxipime, Merrem
A 1:1 randomization scheme based on the infusion duration (continuous over 24 hours or intermittent over 30 minutes) with stratification based on the beta-lactam prescribed (cefepime, meropenem, or piperacillin/tazobactam)
Cefepime, Meropenem, or Piperacillin/TazobactamDrug
Also called Maxipime, Merrem
A 1:1 randomization scheme based on the infusion duration (continuous over 24 hours or intermittent over 30 minutes) with stratification based on the beta-lactam prescribed (cefepime, meropenem, or piperacillin/tazobactam)
| Study group | Role | What they receive |
|---|---|---|
| Continuous Antibiotic Dose Over 24 hours Arm | Active comparator | Subjects will be receiving a continuous dose of antibiotic prescribed by their doctor for the duration they choose. Receives: Drug: Cefepime, Meropenem, or Piperacillin/Tazobactam |
| Intermittent Antibiotic Dose Over 30 minutes | Active comparator | Subjects will be receiving an intermittent dose of antibiotic prescribed by their doctor for the duration they choose. Receives: Drug: Cefepime, Meropenem, or Piperacillin/Tazobactam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gram-negative Bacterial Resistance Emergence Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
Bacterial resistance is defined as new numeric increases (>/=2 fold) in the bacterial MIC during the follow-up period compared to the baseline when starting beta-lactam therapy. MICs were collected from respiratory samples and compared from study enrollment to end of the follow-up period for at least a 2 fold increase in MIC.
Measured: 4 weeks
Secondary outcomes (9)
Superinfection Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens.
Superinfection is defined as the growth of resistant Gram-negative bacteria during the follow-up period which was not isolated in baseline culture. Respiratory cultures during the follow up period were assessed for Gram-negative isolates resistant to the beta-lactams of interest that were not present in the initial respiratory cultures.
Measured: 4 weeks
Microbiologic Eradication Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
Microbiologic eradication is defined as the absence of bacterial growth during the follow-up period with no subsequent positive culture from any site. Respiratory cultures during the follow up period were assessed for the absence of bacterial growth.
Measured: 4 weeks
Clinical Cure at Day 7 of Therapy Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
Clinical cure is the resolution of infection-related symptoms at day 7 of therapy, including normalization of body temperature and white blood cell (WBC) count and taking the patient off mechanical ventilation or vasopressors, and non-initiation of a new antibiotic within 48 hours of stopping the original antibiotic.
Measured: 7 Days
Clinical Cure at the End of Therapy Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
Clinical cure is the resolution of infection-related symptoms at the end of therapy, including normalization of body temperature and white blood cell (WBC) count and taking the patient off mechanical ventilation or vasopressors, and non-initiation of a new antibiotic within 48 hours of stopping the original antibiotic. End of therapy could occur up to 4 weeks after enrollment.
Measured: 4 weeks
Mortality Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
Measured: 4 weeks
Hospital Length of Stay Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens.
Measured: 4 weeks (may extend beyond depending on patient length of stay in hospital)
Intensive Care Unit (ICU) Length of Stay Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
Measured: 4 weeks (may extend beyond depending on patient length of stay in ICU)
Percent of Time Free Drug Concentrations Remain Above the Minimum Inhibitory Concentration (%fT>MIC) in the Dosing Interval Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
Beta-lactam bactericidal efficacy depends upon the percentage of time that free drug concentrations remain above the minimum inhibitory concentration (%fT>MIC) of the pathogen within the dosing interval. Pre-clinical animal studies demonstrate 40-70% fT>MIC is needed for adequate bacterial killing. However, clinical studies suggest higher exposures may be needed, potentially 100%fT>MIC to 100%fT>4xMIC. Patients had beta-lactam concentrations measured as part of therapeutic drug monitoring. Drug exposures were determined using a Bayesian-based software. Infusion arms were compared to determine if %fT>MIC was different between infusion arms.
Measured: 4 weeks
Percent of Time Free Drug Concentrations Remain Above Four Multiples of the Minimum Inhibitory Concentration (%fT>4xMIC) in the Dosing Interval Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
Beta-lactam bactericidal efficacy depends upon the percentage of time that free drug concentrations remain above the minimum inhibitory concentration (%fT>MIC) of the pathogen within the dosing interval. Pre-clinical animal studies demonstrate 40-70% fT>MIC is needed for adequate bacterial killing. However, clinical studies suggest higher exposures may be needed, potentially 100%fT>MIC to 100%fT>4xMIC. Patients had beta-lactam concentrations measured as part of therapeutic drug monitoring. Drug exposures were determined using a Bayesian-based software. Infusion arms were compared to determine if %fT>4xMIC was different between infusion arms.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2021
- Study start17 Dec 2021
- Primary completion28 Feb 2023
- Study completion28 Feb 2023
Why it stopped: Low recruitment.
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 PneumoniaStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Food and Drug Administration (FDA)
- Responsible party
- Sponsor
- Investigators
- Charles Peloquin, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05102162
- Sponsor's protocol ID
- IRB202101979 -A
- Other IDs
- OCR41108
- Status last verified
- May 2023
- First submitted
- 29 Oct 2021
- Last updated
- 12 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Beta-lactam Continuous Versus Intermittent Infusion and Associated Bacterial Resistance and Therapy Outcomes in Critically Ill Patients With Severe Pneumonia
- ClinicalTrials.gov ID
- NCT05102162
- Acronym / sponsor ID
- IRB202101979 -A
- Conditions
- Pneumonia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low recruitment.
- Enrolment
- 35 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Food and Drug Administration (FDA)
- Study start
- 17 Dec 2021 (actual)
- Primary completion
- 28 Feb 2023 (actual)
- Study completion
- 28 Feb 2023 (actual)
- First posted
- 1 Nov 2021 (actual)
- Results
- Posted 12 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study plans to randomize a total of 240 patients infected with Gram-negative bacterial pneumonia to receive beta-lactam (meropenem, cefepime, or piperacillin/tazobactam) continuous or intermittent infusion and collect baseline and regular follow-up respiratory cultures to assess the development of new resistance. The investigators will measure beta-lactam concentration to assess the impact of drug exposure on the bacterial resistance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Continuous Antibiotic Dose Over 24 hours Arm | Active comparator | Drug: Cefepime, Meropenem, or Piperacillin/TazobactamSubjects will be receiving a continuous dose of antibiotic prescribed by their doctor for the duration they choose. |
| Intermittent Antibiotic Dose Over 30 minutes | Active comparator | Drug: Cefepime, Meropenem, or Piperacillin/TazobactamSubjects will be receiving an intermittent dose of antibiotic prescribed by their doctor for the duration they choose. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Admission to the ICU with severe pneumonia (IDSA/ATS 2016/2019): presence of signs, symptoms and confirmatory chest imaging consistent with pneumonia (e.g. fever, cough and pulmonary infiltrate by chest radiograph)
- Age ≥18 years
- Positive respiratory culture (with or without an initial positive rapid identification test and/or Gram stain) for Gram-negative bacteria including, but not limited to, P. aeruginosa, K. pneumoniae, E. coli, S. marcescens, H. influenzae, Enterobacter spp., M. catarrhalis, A. baumannii, Achromobacter spp., P. mirabilis, and/or B. cepacia
- Received within the last 72 hours or will receive meropenem, cefepime, or piperacillin/tazobactam therapy
Key exclusion criteria (6 listed)
- Pregnancy
- Prisoners
- Allergy to the beta-lactams to be administered in this study
- On renal replacement therapy at the time of randomization
- Baseline culture resistant to the beta-lactams in the study
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 |
|---|---|---|
| Cefepime, Meropenem, or Piperacillin/TazobactamAlso: Maxipime, MerremA 1:1 randomization scheme based on the infusion duration (continuous over 24 hours or intermittent over 30 minutes) with stratification based on the beta-lactam prescribed (cefepime, meropenem, or piperacillin/tazobactam) | Drug | Continuous Antibiotic Dose Over 24 hours Arm |
| Cefepime, Meropenem, or Piperacillin/TazobactamAlso: Maxipime, MerremA 1:1 randomization scheme based on the infusion duration (continuous over 24 hours or intermittent over 30 minutes) with stratification based on the beta-lactam prescribed (cefepime, meropenem, or piperacillin/tazobactam) | Drug | Intermittent Antibiotic Dose Over 30 minutes |
Primary outcome
Gram-negative Bacterial Resistance Emergence Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
Time frame: 4 weeks
Bacterial resistance is defined as new numeric increases (>/=2 fold) in the bacterial MIC during the follow-up period compared to the baseline when starting beta-lactam therapy. MICs were collected from respiratory samples and compared from study enrollment to end of the follow-up period for at least a 2 fold increase in MIC.
9 secondary outcomes
Superinfection Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens.
Time frame: 4 weeks
Microbiologic Eradication Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
Time frame: 4 weeks
Clinical Cure at Day 7 of Therapy Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
Time frame: 7 Days
Clinical Cure at the End of Therapy Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
Time frame: 4 weeks
Mortality Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
Time frame: 4 weeks
Hospital Length of Stay Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens.
Time frame: 4 weeks (may extend beyond depending on patient length of stay in hospital)
Intensive Care Unit (ICU) Length of Stay Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
Time frame: 4 weeks (may extend beyond depending on patient length of stay in ICU)
Percent of Time Free Drug Concentrations Remain Above the Minimum Inhibitory Concentration (%fT>MIC) in the Dosing Interval Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
Time frame: 4 weeks
Percent of Time Free Drug Concentrations Remain Above Four Multiples of the Minimum Inhibitory Concentration (%fT>4xMIC) in the Dosing Interval Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
Time frame: 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Charles Peloquin principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Cefepime, Meropenem, or Piperacillin/Tazobactam in people with Pneumonia, run by University of Florida 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 6 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: stopped early, as of the sponsor's last update on 12 Dec 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Dec 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?
Gram-negative Bacterial Resistance Emergence Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens (time frame: 4 weeks). 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 12 Dec 2023; AzTrials last refreshed its copy on 3 Nov 2026.