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

NCT ID: NCT03581370

Last Updated: 2024-09-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-20
• Study Completion Date: 2025-02-28

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

1 hour infusion

Intervention Type: DRUG

Intravenous administration of ceftolozane-tazobactam (ZERBAXA®) : 2000 mg by infusion for 60 minutes every 8 hours.

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.

.

Group Type: EXPERIMENTAL

4 hours infusion

Intervention Type: DRUG

Intravenous administration of ceftolozane-tazobactam (ZERBAXA®) : 2000 mg by infusion for 4 hours every 8 hours

Interventions

1 hour infusion

Intravenous administration of ceftolozane-tazobactam (ZERBAXA®) : 2000 mg by infusion for 60 minutes every 8 hours.

Intervention Type: DRUG

4 hours infusion

Intravenous administration of ceftolozane-tazobactam (ZERBAXA®) : 2000 mg by infusion for 4 hours every 8 hours

Intervention Type: DRUG

Other Intervention Names

Zerbaxa 1 g/0.5 g powder; Zerbaxa 1 g/0.5 g powder

Eligibility 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

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stéphanie RUIZ, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Locations

Service Réanimation Polyvalente - CHU Rangueil

Toulouse, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Stéphanie RUIZ, MD

Role: CONTACT

ruiz.s@chu-toulouse.fr

0561777032

Nathalie ROQUES

Role: CONTACT

roques.n@chu-toulouse.fr

Facility Contacts

Stéphanie RUIZ, MD

Role: primary

Ruiz.stephanie@chu-toulouse.fr

05 61 32 44 64 ext. 33

Bernard GEORGES, MD

Role: backup

Stéphanie RUIZ, MD

Role: backup

Jean-Marie CONIL, MD

Role: backup

David ROUSSET

Role: backup

References

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.

Reference Type: BACKGROUND

PMID: 27999665 (View on PubMed)

Vincent 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.

Reference Type: BACKGROUND

PMID: 27184564 (View on PubMed)

Gelfand 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.

Reference Type: BACKGROUND

PMID: 26021991 (View on PubMed)

Monogue 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.

Reference Type: BACKGROUND

PMID: 27550351 (View on PubMed)

Xiao 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.

Reference Type: BACKGROUND

PMID: 26096377 (View on PubMed)

Other Identifiers

2018-000059-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RC 31/17/0334

Identifier Type: -

Identifier Source: org_study_id