Short Infusion Versus Prolonged Infusion of Ceftolozane-tazobactam Among Patients with Ventilator Associated-pneumonia (CEFTOREA)

Toulouse University Hospital

Status and phase: Enrolling; Phase 3

Conditions: Ventilator-associated Pneumonia

Treatments: Drug: 4 hours infusion; Drug: 1 hour infusion

Study type: Interventional

Funder types: Other

Identifiers

NCT03581370

RC 31/17/0334

2018-000059-42 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 80 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

80 participants in 2 patient groups

1 hour infusion

Active Comparator group

Description:

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.

Treatment:

Drug: 1 hour infusion

4 hours infusion

Experimental group

Description:

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. .

Treatment:

Drug: 4 hours infusion