Short Infusion Versus Prolonged Infusion of Ceftolozane-tazobactam Among Patients With Ventilator Associated-pneumonia (CEFTOREA)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03581370 |
|
Recruitment Status :
Recruiting
First Posted : July 10, 2018
Last Update Posted : March 3, 2021
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Ventilator-associated Pneumonia | Drug: 1 hour infusion Drug: 4 hours infusion | Phase 3 |
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 Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 80 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | The patient will be randomized either in the 4-hours or in the 1-hour infusion group |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | September 20, 2018 |
| Estimated Primary Completion Date : | February 2023 |
| Estimated Study Completion Date : | February 2023 |
| Arm | Intervention/treatment |
|---|---|
|
Active Comparator: 1 hour infusion
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. |
Drug: 1 hour infusion
Intravenous administration of ceftolozane-tazobactam (ZERBAXA®) : 2000 mg by infusion for 60 minutes every 8 hours.
Other Name: Zerbaxa 1 g/0.5 g powder |
|
Experimental: 4 hours infusion
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. . |
Drug: 4 hours infusion
Intravenous administration of ceftolozane-tazobactam (ZERBAXA®) : 2000 mg by infusion for 4 hours every 8 hours
Other Name: Zerbaxa 1 g/0.5 g powder |
- 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.
- Percentage of patients with concentrations greater than 5*Minimum inhibitory Concentration [ Time Frame: Time between two administrations (8 hours) ]The percentage of patients with concentrations greater than 5*Minimum inhibitory Concentration over an 8-hour post administration interval.
- Bactericidal rate [ Time Frame: at Day 10 ]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
- Percentage of patients recovering at the end of the treatment period [ Time Frame: at Day 10 ]Number of patients recovering in relation to the total number of patients
- Percentage of patients failing at the end of the treatment period [ Time Frame: at Day 10 ]Number of patients failing in relation to the total number of patients
- Number of days without artificial ventilation [ Time Frame: at Day 28 ]The number of days without artificial ventilation
- The duration of hospitalization [ Time Frame: at Day 28 ]the duration of hospitalization in number of day
- Survival at D28 [ Time Frame: at Day 28 ]survival in number of patient alive
- The alveolar concentration of Ceftolozane-Tazobactam [ Time Frame: between 24 hour and 48 hour after time 0 ]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
- Evaluation of the serious adverse events [ Time Frame: Day 28 ]Evaluation of the serious adverse events at the doses and regimen recommended in the trial
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
inclusion criteria
- 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
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03581370
| Contact: Stéphanie RUIZ, MD | 33561777032 | ruiz.s@chu-toulouse.fr | |
| Contact: Nathalie ROQUES | roques.n@chu-toulouse.fr |
| France | |
| Service Réanimation Polyvalente - CHU Rangueil | Recruiting |
| Toulouse, France, 31059 | |
| Contact: Stéphanie RUIZ, MD 05 61 32 44 64 ext 33 Ruiz.stephanie@chu-toulouse.fr | |
| Sub-Investigator: Bernard GEORGES, MD | |
| Principal Investigator: Stéphanie RUIZ, MD | |
| Sub-Investigator: Jean-Marie CONIL, MD | |
| Sub-Investigator: David ROUSSET | |
| Principal Investigator: | Stéphanie RUIZ, MD | University Hospital, Toulouse |
| Responsible Party: | University Hospital, Toulouse |
| ClinicalTrials.gov Identifier: | NCT03581370 |
| Other Study ID Numbers: |
RC 31/17/0334 2018-000059-42 ( EudraCT Number ) |
| First Posted: | July 10, 2018 Key Record Dates |
| Last Update Posted: | March 3, 2021 |
| Last Verified: | March 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
|
Pneumonia Pseudomonas aeruginosa pharmacokinetics |
|
Pneumonia Pneumonia, Ventilator-Associated Respiratory Tract Infections Infections Lung Diseases Respiratory Tract Diseases Healthcare-Associated Pneumonia Cross Infection Iatrogenic Disease Disease Attributes Pathologic Processes |
Ceftolozane, tazobactam drug combination Cephalosporins Penicillanic Acid Anti-Infective Agents, Urinary Anti-Infective Agents Renal Agents Anti-Bacterial Agents beta-Lactamase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |