Gram-Negative Bacterial InfectionsRESTARTNCT05171257
Quantifying Gram-negative Resistance to Empiric Therapy in the Intensive Care Unit
An observational study of Gram-Negative Bacterial Infections, run by Methodist Health System at 1 site in United States.
Trial summary
Antimicrobial resistance is a global health emergency estimated to be responsible for 700,000 deaths per year worldwide, and it is well known that previous antibiotic exposure is the single most contributing factor. For example, the use of non-antipseudomonal agents can increase risk for any P. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gram-Negative Bacterial Infections
- What is being tested?
- IV antibiotic treatment from prior and differing IV antibiotic treatment
- Type of treatment
- Injection or infusion
- How many people
- 197 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Oct 2021to 14 Jul 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
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
Study population: sample size of 242 (121 patients in each group)
Who may be able to join
- ≥18 years of age
- GNP pneumonia or bacteremia during hospital admission
- Previous IV antibiotics for at least 48 hours in the past 90 days
- Culture MIC data available
Who cannot join
- Patients with a history of isolate resistance in the previous six months to antibiotics being studied
- Patients that received antibiotics within five days prior to study inclusion
- Patients on more than one anti-pseudomonal beta-lactam antibiotics (excluding emergency department doses) during previous exposure
Trial locations and contacts
1 site in 1 country.
United States1 site
Methodist Dallas Medical Center
Dallas, Texas, 75203
About this study
Official title: Quantifying Gram-negative Resistance to Empiric Therapy in the Intensive Care Unit - Repeat ExpoSure to AntimicRobial Therapy (RESTART)
Antimicrobial resistance is a global health emergency estimated to be responsible for 700,000 deaths per year worldwide, and it is well known that previous antibiotic exposure is the single most contributing factor. For example, the use of non-antipseudomonal agents can increase risk for any P. aeruginosa strain; however, the use of an agent with antipseudomonal activity would select for resistance to that particular antimicrobial agent or class. Demonstrated that each additional day of exposure to any antipseudomonal beta-lactam is associated with an increased risk of new resistance development.
The study seeks to determine whether the choice of empiric therapy (i.e., the same agent versus a different agent from prior antibiotic exposure) has any effect on the likelihood of in vitro activity against GN pathogens (GNPs) in a subsequent infection.
Read the detailed description
Antimicrobials are the most commonly prescribed drugs in medicine, resulting in inappropriate use in approximately 50% of cases Misuse can have devastating effects through resistance development which further complicates selection of appropriate empiric antibiotics. In cases of severe illness, it is easy for clinicians to rely on broad spectrum antibiotics to cover the majority of likely pathogens when dealing with a presumed bacterial infection. However, this practice perpetuates the cycle of resistance. Inappropriate empiric therapy is associated with worse outcomes in resistant Gram-negative (GN) bacteremia and pneumonia, so clinicians should strive for targeted coverage that is specific to the pathogen of interest when possible. Johnson et al. showed that patients with recent antibiotic exposure had greater inappropriate initial antimicrobial therapy (45.4% vs. 21.2%; p < 0.001) and higher in-hospital mortality (51.3% vs. 34.0%; p < 0.001) compared with patients without recent antibiotic exposure.
The 2020 Infectious Diseases Society of America (IDSA) Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections reports an increased risk of resistance with antibiotic exposure in the past 30 days. Additionally, expert opinion prompts consideration of empiric coverage with a GN agent from a different class that offers comparable spectrum of activity from previous exposure. The 2019 Community-acquired Pneumonia (CAP) Guidelines from the American Thoracic Society and IDSA lists prior antibiotic use in the last 90 days as a risk factor for P. aeruginosa.The 2016 Hospital-acquired and Ventilator-associated Pneumonia (HAP, VAP) Guidelines from IDSA, list antibiotic use in the past 90 days as a risk factor for P. aeruginosa and other GN organisms in HAP. Additionally, antibiotic use in the past 90 days is listed as having an association with increased risk of multi-drug resistant VAP. The CAP, HAP, and VAP Guidelines do not mention using the same versus different agent as empiric choice if previous antibiotic exposure is to an anti-pseudomonal agent.
- Conditions
- Gram-Negative Bacterial Infections
- Being tested
- IV antibiotic treatment from prior, differing IV antibiotic treatment
- Medical subject headings
- Gram-Negative Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IV antibiotic treatment from priorDrug
patients receiving same IV antibiotic treatment from prior
differing IV antibiotic treatmentDrug
patients receiving differing IV antibiotics from prior
| Study group | Role | What they receive |
|---|---|---|
| repeat group | patients receiving empiric therapy with the same IV antibiotics from prior Receives: Drug: IV antibiotic treatment from prior | |
| change group | patients receiving differing IV antibiotics from prior Receives: Drug: differing IV antibiotic treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rates of resistance
Rates of resistance in patients receiving empiric therapy with the same IV antibiotics from prior (repeat group) compared to rates of resistance in patients receiving differing IV antibiotics from prior (change group)
Measured: charts from 4/1/2017 to 3/31/2021
Secondary outcomes (1)
Intensive Care Unite LOS(ICU LOS)
Intensive Care Unite LOS(ICU LOS)
Measured: charts from 4/1/2017 to 3/31/2021
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2021
- Study start19 Oct 2021
- Primary completion14 Jul 2025
- Study completion14 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gram-Negative Bacterial InfectionsStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 197 participants (actual)
Sponsor and investigators
- Lead sponsor
- Methodist Health System
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mathew Crotty, MD, Principal investigator, Methodist
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05171257
- Sponsor's protocol ID
- 038.PHA.2021.D
- Acronym
- RESTART
- Status last verified
- Mar 2026
- First submitted
- 9 Dec 2021
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quantifying Gram-negative Resistance to Empiric Therapy in the Intensive Care Unit - Repeat ExpoSure to AntimicRobial Therapy (RESTART)
- ClinicalTrials.gov ID
- NCT05171257
- Acronym / sponsor ID
- RESTART / 038.PHA.2021.D
- Conditions
- Gram-Negative Bacterial Infections
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 197 participants (actual)
- Lead sponsor
- Methodist Health SystemUniversity, hospital or other
- Study start
- 19 Oct 2021 (actual)
- Primary completion
- 14 Jul 2025 (actual)
- Study completion
- 14 Jul 2025 (actual)
- First posted
- 28 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Antimicrobial resistance is a global health emergency estimated to be responsible for 700,000 deaths per year worldwide, and it is well known that previous antibiotic exposure is the single most contributing factor. For example, the use of non-antipseudomonal agents can increase risk for any P. aeruginosa strain; however, the use of an agent with antipseudomonal activity would select for resistance to that particular antimicrobial agent or class. Demonstrated that each additional day of exposure to any antipseudomonal beta-lactam is associated with an increased risk of new resistance development.
The study seeks to determine whether the choice of empiric therapy (i.e., the same agent versus a different agent from prior antibiotic exposure) has any effect on the likelihood of in vitro activity against GN pathogens (GNPs) in a subsequent infection.
Detailed description
Antimicrobials are the most commonly prescribed drugs in medicine, resulting in inappropriate use in approximately 50% of cases Misuse can have devastating effects through resistance development which further complicates selection of appropriate empiric antibiotics. In cases of severe illness, it is easy for clinicians to rely on broad spectrum antibiotics to cover the majority of likely pathogens when dealing with a presumed bacterial infection. However, this practice perpetuates the cycle of resistance. Inappropriate empiric therapy is associated with worse outcomes in resistant Gram-negative (GN) bacteremia and pneumonia, so clinicians should strive for targeted coverage that is specific to the pathogen of interest when possible. Johnson et al. showed that patients with recent antibiotic exposure had greater inappropriate initial antimicrobial therapy (45.4% vs. 21.2%; p < 0.001) and higher in-hospital mortality (51.3% vs. 34.0%; p < 0.001) compared with patients without recent antibiotic exposure.
The 2020 Infectious Diseases Society of America (IDSA) Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections reports an increased risk of resistance with antibiotic exposure in the past 30 days. Additionally, expert opinion prompts consideration of empiric coverage with a GN agent from a different class that offers comparable spectrum of activity from previous exposure. The 2019 Community-acquired Pneumonia (CAP) Guidelines from the American Thoracic Society and IDSA lists prior antibiotic use in the last 90 days as a risk factor for P. aeruginosa.The 2016 Hospital-acquired and Ventilator-associated Pneumonia (HAP, VAP) Guidelines from IDSA, list antibiotic use in the past 90 days as a risk factor for P. aeruginosa and other GN organisms in HAP. Additionally, antibiotic use in the past 90 days is listed as having an association with increased risk of multi-drug resistant VAP. The CAP, HAP, and VAP Guidelines do not mention using the same versus different agent as empiric choice if previous antibiotic exposure is to an anti-pseudomonal agent.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| repeat group | – | Drug: IV antibiotic treatment from priorpatients receiving empiric therapy with the same IV antibiotics from prior |
| change group | – | Drug: differing IV antibiotic treatmentpatients receiving differing IV antibiotics from prior |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- sample size of 242 (121 patients in each group)
Key inclusion criteria (4 listed)
- ≥18 years of age
- GNP pneumonia or bacteremia during hospital admission
- Previous IV antibiotics for at least 48 hours in the past 90 days
- Culture MIC data available
Key exclusion criteria (3 listed)
- Patients with a history of isolate resistance in the previous six months to antibiotics being studied
- Patients that received antibiotics within five days prior to study inclusion
- Patients on more than one anti-pseudomonal beta-lactam antibiotics (excluding emergency department doses) during previous exposure
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 |
|---|---|---|
| IV antibiotic treatment from priorpatients receiving same IV antibiotic treatment from prior | Drug | repeat group |
| differing IV antibiotic treatmentpatients receiving differing IV antibiotics from prior | Drug | change group |
Primary outcome
Rates of resistance
Time frame: charts from 4/1/2017 to 3/31/2021
Rates of resistance in patients receiving empiric therapy with the same IV antibiotics from prior (repeat group) compared to rates of resistance in patients receiving differing IV antibiotics from prior (change group)
1 secondary outcome
Intensive Care Unite LOS(ICU LOS)
Time frame: charts from 4/1/2017 to 3/31/2021
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- 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.
Mathew Crotty, MD principal investigator
Methodist
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Gram-Negative Bacterial Infections, run by Methodist Health System 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 3 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 27 Mar 2026. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Rates of resistance (time frame: charts from 4/1/2017 to 3/31/2021). 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 27 Mar 2026.