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

NCT03581370 | Recruiting Phase 3

• 2 other identifiers: RC 31/17/03342018-000059-42
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Ventilator-associated Pneumonia

Keywords

Pneumonia; Pseudomonas aeruginosa; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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.

  Time between two administrations (8 hours)

Secondary Outcomes (9)

• Percentage of patients with concentrations greater than 5*Minimum inhibitory Concentration

  Time between two administrations (8 hours)

• Bactericidal rate

  at Day 10

• Percentage of patients recovering at the end of the treatment period

  at Day 10

• Percentage of patients failing at the end of the treatment period

  at Day 10

• Number of days without artificial ventilation

  at Day 28

Study Arms (2)

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.

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. .

Drug: 4 hours infusion

Interventions

1 hour infusion DRUG

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

Also known as: Zerbaxa 1 g/0.5 g powder

1 hour infusion

4 hours infusion DRUG

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

Also known as: Zerbaxa 1 g/0.5 g powder

4 hours infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (1)

Service Réanimation Polyvalente - CHU Rangueil

Toulouse, 31059, France

RECRUITING

Related Publications (5)

• 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.

  PMID: 27999665 BACKGROUND

• 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.

  PMID: 27184564 BACKGROUND

• 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.

  PMID: 26021991 BACKGROUND

• 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.

  PMID: 27550351 BACKGROUND

• 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.

  PMID: 26096377 BACKGROUND

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated; Pneumonia; Pseudomonas Infections

Interventions

ceftolozane, tazobactam drug combination; Powders

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Stéphanie RUIZ, MD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stéphanie RUIZ, MD

CONTACT

0561777032; ruiz.s@chu-toulouse.fr

Nathalie ROQUES

CONTACT

roques.n@chu-toulouse.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The patient will be randomized either in the 4-hours or in the 1-hour infusion group

Study Record Dates

• First Submitted: June 26, 2018
• First Posted: July 10, 2018
• Study Start: September 20, 2018
• Primary Completion: February 1, 2025
• Study Completion: February 1, 2025
• Last Updated: September 25, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)