Ventilator-associated PneumoniaPhase 3CEFTOREANCT03581370
Short Infusion Versus Prolonged Infusion of Ceftolozane-tazobactam Among Patients with Ventilator Associated-pneumonia
A Phase 3 study testing 1 hour infusion and 4 hours infusion in people with Ventilator-associated Pneumonia, run by University Hospital, Toulouse at 1 site in France.
Trial summary
The main objective of this study is to compare the median exposures at pharmacokinetic equilibrium of the two modalities of administration: 4-hours infusion of ceftolozane-tazobactam at a dosage of 2 gram three times a day vs 1-hour infusion of 2 gram three times a day. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ventilator-associated Pneumonia
- What is being tested?
- 1 hour infusion and 4 hours infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteFrance
- Study dates
- 20 Sep 2018to Feb 2025
- Phase
- Phase 3
- 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
Who may be able to join
- patients with ventilator associated-pneumonia to Pseudomonas aeruginosa
- patients hospitalized in intensive care units
- Pseudomonas aeruginosa susceptible to ceftolozane-tazobactam
- Simplified Acute Physiological Score II (SAPS II () > 20
- Expected duration of survival > 7 days
- Informed consent of the patient or, failing that, the patient's close or trustworthy person
Show all 16Show fewer
- Affiliated to a social security scheme or equivalent
- Non inclusion criteria:
- history of allergy to one of the two molecules
- history of allergy to betalactamines
- Strain Isolated resistant to Ceftolozane-Tazobactam combination
- Renal insufficiency with a glomerular filtration rate evaluated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) < 50 ml/min
- Patient on dialysis or under continuous hemodiafiltration
- pregnant or nursing women
- patient benefiting from a system of legal protection for adults
- patient with active immunodepression.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
Nathalie ROQUES contact
France1 site, 1 recruiting
- Recruiting
Service Réanimation Polyvalente - CHU Rangueil
Toulouse, 31059
Stéphanie RUIZ, MD, 05 61 32 44 64 ext. 33, Ruiz.stephanie@chu-toulouse.fr
Bernard GEORGES, MD
About this study
Official title: Comparison of Short Infusion Versus Prolonged Infusion of Ceftolozane-tazobactam Among Patients with Ventilator Associated-pneumonia to Pseudomonas Aeruginosa in Intensive Care Units
The main objective of this study is to compare the median exposures at pharmacokinetic equilibrium of the two modalities of administration: 4-hours infusion of ceftolozane-tazobactam at a dosage of 2 gram three times a day vs 1-hour infusion of 2 gram three times a day.
Read the detailed description
Intensive care unit patients with ventilator associated-pneumonia often develop severe and rapidly life threatening Gram-negative Bacillus infections. Moreover, they present pathophysiological disturbances responsible for major pharmacokinetic changes (volume of distribution and glomerular filtration) which may lead to drugs under-exposure. Any delay in management or inadequate antibiotic therapy can have serious consequences in terms of prognosis. The association ceftolozane-tazobactam is an alternative to carbapenems in documented infections. Ceftolozane is a new cephalosporin, marketed, in combination with tazobactam (beta-lactamase inhibitor) under the name ZERBAXA®. ZERBAXA® is active on Gram-negative Bacillus, including Pseudomonas aeruginosa.
This is a prospective, randomized, open pharmacokinetic/pharmacodynamic study that compares two modalities of administration of a novel antibiotic, ZERBAXA® ceftolozane-tazobactam, by 4-hours infusion at the dosage of 2 gram three times a day vs. 1-hour infusion at the dosage of 2 g three times a day, among patients with ventilator associated-pneumonia to Pseudomonas aeruginosa.
The patient will be randomized either in the 4-hours or in the 1-hour infusion group. Follow up visits are daily for any intensive care patient. Those provided for biomedical research are carried out during the treatment period, at Day 15 and Day 28. For the pharmacokinetic study, 7 blood samples will be collected from 24 hours to 48 hours after the first ZERBAXA® administration.
- Conditions
- Ventilator-associated Pneumonia
- Being tested
- 1 hour infusion, 4 hours infusion
- Keywords
- Pneumonia, Pseudomonas aeruginosa, pharmacokinetics
- Medical subject headings
- Pneumonia, Ventilator-Associated, Pneumonia, Pseudomonas Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1 hour infusionDrug
Also called Zerbaxa 1 g/0.5 g powder
Intravenous administration of ceftolozane-tazobactam (ZERBAXA®) : 2000 mg by infusion for 60 minutes every 8 hours.
4 hours infusionDrug
Also called Zerbaxa 1 g/0.5 g powder
Intravenous administration of ceftolozane-tazobactam (ZERBAXA®) : 2000 mg by infusion for 4 hours every 8 hours
| Study group | Role | What they receive |
|---|---|---|
| 1 hour infusion | Active comparator | The first group corresponds to 1-hour infusion : First administration of ceftolozane-tazobactam with 2000 mg by infusion for 60 minutes every 8 hours.
24h after this first administration, 7 blood samples will be collected at Hour 24, Hour 25, Hour 26, Hour 28, Hour 30, Hour 32 and Hour 48. Receives: Drug: 1 hour infusion |
| 4 hours infusion | Experimental | The second group corresponds to 4-hours infusion: First administration of ceftolozane-tazobactam with 2000 mg by infusion for 4 hours every 8 hours. 24h after this first administration, 7 blood samples will be collected at Hour 24, Hour 25, Hour 26, Hour 28, Hour 30, Hour 32 and Hour 48.
. Receives: Drug: 4 hours infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time that the concentration spends above 5 Minimum inhibitory Concentration (T>5*MIC)
The primary endpoint is the time that the concentration spends above 5* Minimum inhibitory Concentration, expressed as a percentage of the time interval between two administrations. The T>5* Minimum inhibitory Concentration will be determined for each patient from the concentration profile measured over an 8-hour post-administration interval. Since protein binding is low (<20%), the total concentration (sum of free form and plasma protein bound) will be used as a marker for free concentration. Therefore, the T>5* Minimum inhibitory Concentration will be calculated from the total concentrations. Our study will focus on only Pseudomonas aeruginosa Pneumonia acquired under mechanical ventilation with a critical Minimum inhibitory Concentration of 4 mg/l, T>5* Minimum inhibitory Concentration will then correspond to a residual serum concentration of 20 mg/l.
Measured: Time between two administrations (8 hours)
Secondary outcomes (9)
Percentage of patients with concentrations greater than 5*Minimum inhibitory Concentration
The percentage of patients with concentrations greater than 5*Minimum inhibitory Concentration over an 8-hour post administration interval.
Measured: Time between two administrations (8 hours)
Bactericidal rate
Bactericidal rate obtained in vitro using the Hollow Fiber device. This rate is determined for broncho-alveolar concentrations estimated in patients with pneumonia acquired during ventilation
Measured: at Day 10
Percentage of patients recovering at the end of the treatment period
Number of patients recovering in relation to the total number of patients
Measured: at Day 10
Percentage of patients failing at the end of the treatment period
Number of patients failing in relation to the total number of patients
Measured: at Day 10
Number of days without artificial ventilation
The number of days without artificial ventilation
Measured: at Day 28
The duration of hospitalization
the duration of hospitalization in number of day
Measured: at Day 28
Survival at D28
survival in number of patient alive
Measured: at Day 28
The alveolar concentration of Ceftolozane-Tazobactam
The alveolar concentration of Ceftolozane-Tazobactam from a sample of the alveolar fluid produced by bronchial fibroscopy between the 24th hour and the 48th hour
Measured: between 24 hour and 48 hour after time 0
Evaluation of the serious adverse events
Evaluation of the serious adverse events at the doses and regimen recommended in the trial
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2018
- Study start20 Sep 2018
- Primary completionFeb 2025 (estimated)
- Study completionFeb 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Ventilator-associated PneumoniaStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The patient will be randomized either in the 4-hours or in the 1-hour infusion group
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stéphanie RUIZ, MD, Principal investigator, University Hospital, Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03581370
- Sponsor's protocol ID
- RC 31/17/0334
- Other IDs
- 2018-000059-42, 2018
- Acronym
- CEFTOREA
- Status last verified
- Sep 2024
- First submitted
- 26 Jun 2018
- Last updated
- 25 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Colomb-Cotinat M, Lacoste J, Brun-Buisson C, Jarlier V, Coignard B, Vaux S. Estimating the morbidity and mortality associated with infections due to multidrug-resistant bacteria (MDRB), France, 2012. Antimicrob Resist Infect Control. 2016 Dec 12;5:56. doi: 10.1186/s13756-016-0154-z. eCollection 2016.
PubMed 27999665Vincent JL, Bassetti M, Francois B, Karam G, Chastre J, Torres A, Roberts JA, Taccone FS, Rello J, Calandra T, De Backer D, Welte T, Antonelli M. Advances in antibiotic therapy in the critically ill. Crit Care. 2016 May 17;20(1):133. doi: 10.1186/s13054-016-1285-6.
PubMed 27184564Gelfand MS, Cleveland KO. Ceftolozane/Tazobactam Therapy of Respiratory Infections due to Multidrug-Resistant Pseudomonas aeruginosa. Clin Infect Dis. 2015 Sep 1;61(5):853-5. doi: 10.1093/cid/civ411. Epub 2015 May 28. No abstract available.
PubMed 26021991Monogue ML, Pettit RS, Muhlebach M, Cies JJ, Nicolau DP, Kuti JL. Population Pharmacokinetics and Safety of Ceftolozane-Tazobactam in Adult Cystic Fibrosis Patients Admitted with Acute Pulmonary Exacerbation. Antimicrob Agents Chemother. 2016 Oct 21;60(11):6578-6584. doi: 10.1128/AAC.01566-16. Print 2016 Nov.
PubMed 27550351Xiao AJ, Miller BW, Huntington JA, Nicolau DP. Ceftolozane/tazobactam pharmacokinetic/pharmacodynamic-derived dose justification for phase 3 studies in patients with nosocomial pneumonia. J Clin Pharmacol. 2016 Jan;56(1):56-66. doi: 10.1002/jcph.566. Epub 2015 Aug 25.
PubMed 26096377
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Short Infusion Versus Prolonged Infusion of Ceftolozane-tazobactam Among Patients with Ventilator Associated-pneumonia to Pseudomonas Aeruginosa in Intensive Care Units
- ClinicalTrials.gov ID
- NCT03581370
- Acronym / sponsor ID
- CEFTOREA / RC 31/17/0334
- Conditions
- Ventilator-associated Pneumonia
- Keywords
- Pneumonia, Pseudomonas aeruginosa, pharmacokinetics
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Study start
- 20 Sep 2018 (actual)
- Primary completion
- Feb 2025 (estimated)
- Study completion
- Feb 2025 (estimated)
- First posted
- 10 Jul 2018 (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.
The main objective of this study is to compare the median exposures at pharmacokinetic equilibrium of the two modalities of administration: 4-hours infusion of ceftolozane-tazobactam at a dosage of 2 gram three times a day vs 1-hour infusion of 2 gram three times a day.
Detailed description
Intensive care unit patients with ventilator associated-pneumonia often develop severe and rapidly life threatening Gram-negative Bacillus infections. Moreover, they present pathophysiological disturbances responsible for major pharmacokinetic changes (volume of distribution and glomerular filtration) which may lead to drugs under-exposure. Any delay in management or inadequate antibiotic therapy can have serious consequences in terms of prognosis. The association ceftolozane-tazobactam is an alternative to carbapenems in documented infections. Ceftolozane is a new cephalosporin, marketed, in combination with tazobactam (beta-lactamase inhibitor) under the name ZERBAXA®. ZERBAXA® is active on Gram-negative Bacillus, including Pseudomonas aeruginosa.
This is a prospective, randomized, open pharmacokinetic/pharmacodynamic study that compares two modalities of administration of a novel antibiotic, ZERBAXA® ceftolozane-tazobactam, by 4-hours infusion at the dosage of 2 gram three times a day vs. 1-hour infusion at the dosage of 2 g three times a day, among patients with ventilator associated-pneumonia to Pseudomonas aeruginosa.
The patient will be randomized either in the 4-hours or in the 1-hour infusion group. Follow up visits are daily for any intensive care patient. Those provided for biomedical research are carried out during the treatment period, at Day 15 and Day 28. For the pharmacokinetic study, 7 blood samples will be collected from 24 hours to 48 hours after the first ZERBAXA® administration.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The patient will be randomized either in the 4-hours or in the 1-hour infusion group
| Arm | Type | Receives |
|---|---|---|
| 1 hour infusion | Active comparator | Drug: 1 hour infusionThe first group corresponds to 1-hour infusion : First administration of ceftolozane-tazobactam with 2000 mg by infusion for 60 minutes every 8 hours. 24h after this first administration, 7 blood samples will be collected at Hour 24, Hour 25, Hour 26, Hour 28, Hour 30, Hour 32 and Hour 48. |
| 4 hours infusion | Experimental | Drug: 4 hours infusionThe second group corresponds to 4-hours infusion: First administration of ceftolozane-tazobactam with 2000 mg by infusion for 4 hours every 8 hours. 24h after this first administration, 7 blood samples will be collected at Hour 24, Hour 25, Hour 26, Hour 28, Hour 30, Hour 32 and Hour 48. . |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- patients with ventilator associated-pneumonia to Pseudomonas aeruginosa
- patients hospitalized in intensive care units
- Pseudomonas aeruginosa susceptible to ceftolozane-tazobactam
- Simplified Acute Physiological Score II (SAPS II () > 20
- Expected duration of survival > 7 days
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| 1 hour infusionAlso: Zerbaxa 1 g/0.5 g powderIntravenous administration of ceftolozane-tazobactam (ZERBAXA®) : 2000 mg by infusion for 60 minutes every 8 hours. | Drug | 1 hour infusion |
| 4 hours infusionAlso: Zerbaxa 1 g/0.5 g powderIntravenous administration of ceftolozane-tazobactam (ZERBAXA®) : 2000 mg by infusion for 4 hours every 8 hours | Drug | 4 hours infusion |
Primary outcome
Time that the concentration spends above 5 Minimum inhibitory Concentration (T>5*MIC)
Time frame: Time between two administrations (8 hours)
The primary endpoint is the time that the concentration spends above 5* Minimum inhibitory Concentration, expressed as a percentage of the time interval between two administrations. The T>5* Minimum inhibitory Concentration will be determined for each patient from the concentration profile measured over an 8-hour post-administration interval. Since protein binding is low (<20%), the total concentration (sum of free form and plasma protein bound) will be used as a marker for free concentration. Therefore, the T>5* Minimum inhibitory Concentration will be calculated from the total concentrations. Our study will focus on only Pseudomonas aeruginosa Pneumonia acquired under mechanical ventilation with a critical Minimum inhibitory Concentration of 4 mg/l, T>5* Minimum inhibitory Concentration will then correspond to a residual serum concentration of 20 mg/l.
9 secondary outcomes
Percentage of patients with concentrations greater than 5*Minimum inhibitory Concentration
Time frame: Time between two administrations (8 hours)
Bactericidal rate
Time frame: at Day 10
Percentage of patients recovering at the end of the treatment period
Time frame: at Day 10
Percentage of patients failing at the end of the treatment period
Time frame: at Day 10
Number of days without artificial ventilation
Time frame: at Day 28
The duration of hospitalization
Time frame: at Day 28
Survival at D28
Time frame: at Day 28
The alveolar concentration of Ceftolozane-Tazobactam
Time frame: between 24 hour and 48 hour after time 0
Evaluation of the serious adverse events
Time frame: Day 28
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2024.
- Background: PubMed 27999665Colomb-Cotinat M, Lacoste J, Brun-Buisson C, Jarlier V, Coignard B, Vaux S. Estimating the morbidity and mortality associated with infections due to multidrug-resistant bacteria (MDRB), France, 2012. Antimicrob Resist Infect Control. 2016 Dec 12;5:56. doi: 10.1186/s13756-016-0154-z. eCollection 2016.
- Background: PubMed 27184564Vincent JL, Bassetti M, Francois B, Karam G, Chastre J, Torres A, Roberts JA, Taccone FS, Rello J, Calandra T, De Backer D, Welte T, Antonelli M. Advances in antibiotic therapy in the critically ill. Crit Care. 2016 May 17;20(1):133. doi: 10.1186/s13054-016-1285-6.
- Background: PubMed 26021991Gelfand MS, Cleveland KO. Ceftolozane/Tazobactam Therapy of Respiratory Infections due to Multidrug-Resistant Pseudomonas aeruginosa. Clin Infect Dis. 2015 Sep 1;61(5):853-5. doi: 10.1093/cid/civ411. Epub 2015 May 28. No abstract available.
- Background: PubMed 27550351Monogue ML, Pettit RS, Muhlebach M, Cies JJ, Nicolau DP, Kuti JL. Population Pharmacokinetics and Safety of Ceftolozane-Tazobactam in Adult Cystic Fibrosis Patients Admitted with Acute Pulmonary Exacerbation. Antimicrob Agents Chemother. 2016 Oct 21;60(11):6578-6584. doi: 10.1128/AAC.01566-16. Print 2016 Nov.
- Background: PubMed 26096377Xiao AJ, Miller BW, Huntington JA, Nicolau DP. Ceftolozane/tazobactam pharmacokinetic/pharmacodynamic-derived dose justification for phase 3 studies in patients with nosocomial pneumonia. J Clin Pharmacol. 2016 Jan;56(1):56-66. doi: 10.1002/jcph.566. Epub 2015 Aug 25.
- 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.
Nathalie ROQUES contact
Stéphanie RUIZ, MD principal investigator
University Hospital, Toulouse
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 1 hour infusion and 4 hours infusion in people with Ventilator-associated Pneumonia, run by University Hospital, Toulouse at 1 site in France.
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 16 inclusion and 0 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: status not confirmed, as of the sponsor's last update on 25 Sep 2024. 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 France. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Stéphanie RUIZ, MD (0561777032, ruiz.s@chu-toulouse.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time that the concentration spends above 5 Minimum inhibitory Concentration (T>5*MIC) (time frame: Time between two administrations (8 hours)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03581370, which also lists 5 linked publications.
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 25 Sep 2024.