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Pharmacological Comparison of Continuous and Intermittent Infusions of Cloxacillin (CLOXA Continue)

Primary Purpose

Infection, Methicillin Susceptible Staphylococcus Aureus Infection, Cloxacillin Treatment

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Modification for administration mode of cloxacillin antibiotic
Sponsored by
Centre Hospitalier Universitaire de Nice
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Staphylococcus aureus sensitive to methicillin and to be treated with cloxacillin by injectable antibiotic monotherapy For patients with Osteo-articular infection on material

    • Presence of a fistula in contact with the prosthesis or implant.
    • Pus in the joint or in contact with the prosthesis or implant
    • Presence of at least 1 positive sample (1 sampling by articular puncture or 1 peroperative sampling or by blood culture)
    • A histological analysis of the peri-prosthetic osteo-articular tissue which is the object of acute inflammation is a strong argument in favor of an Osteo-articular infection on material

For spondylodiscitis

  • Culture of a disco-vertebral biopsy puncture to isolate a methicillin sensitive S. aureus
  • Positive haemocultures for S. aureus sensitive to methicillin with imaging examination (CT or MRI of the spine) showing images of spondylodiscitis

For primitive arthritis :

  • Culture of a positive methicillin-sensitive S. aureus articular fluid puncture
  • Cultivation of a methicillin-sensitive S. aureus-positive surgical joint lavage fluid

For osteitis the diagnosis is based on the following criterion:

*Culture of surgical specimens from a focal zone of methicillin-sensitive S. aureus-positive osteitis

Exclusion Criteria:

  • Allergy to betalactamines
  • Taking penicillin M within 36 hours before inclusion Renal function impaired with a glomerular filtration rate measured by MDRD formula of less than 30 ml / min
  • Patient with renal function expected to change within 6 days of inclusion

  • Hepatocellular insufficiency, whatever the degree

    -*Methotrexate intake

  • Polytransfused (more than 2 CGR) in the previous week
  • Patients requiring resuscitation

Sites / Locations

  • CHU de Nice

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Intermittent administration of cloxacillin

continuous administration of cloxacillin

Arm Description

Outcomes

Primary Outcome Measures

The equivalence of the Pharmacokinetic-Pharmacodynamic indicators commonly used for the study of betalactamines: T> minimal inhibitory concentration
The equivalence of the Pharmacokinetic-Pharmacodynamic indicators commonly used for the study of betalactamines: the area under the curve (AUC) / minimal inhibitory concentration

Secondary Outcome Measures

Full Information

First Posted
July 28, 2017
Last Updated
April 19, 2019
Sponsor
Centre Hospitalier Universitaire de Nice
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1. Study Identification

Unique Protocol Identification Number
NCT03246360
Brief Title
Pharmacological Comparison of Continuous and Intermittent Infusions of Cloxacillin
Acronym
CLOXA Continue
Official Title
Pharmacological Comparison of Continuous and Intermittent Infusions of Cloxacillin During Bone and Joint Infections: a Prospective, Randomized, Open-label, Monocentric Crossover Study.
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
November 23, 2017 (Actual)
Primary Completion Date
November 23, 2017 (Actual)
Study Completion Date
September 18, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Nice

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Our objective is to establish pharmacological equivalence of intermittent and continuous infusion of cloxacillin during methicillin-susceptible Staphylococcus aureus (MSSA) bone and joint infections (BJI). Twelve patients suffering MSSA BJI will receive both administration modalities and serum concentrations of cloxacillin will be determined after 3 days of II and 3 days of continuous infusion in a prospective, randomized, open-label, monocentric crossover study design.
Detailed Description
Introduction Staphylococcus aureus is the main causative agent of bone and joint infections (BJI). More than 80% of the strains isolated in France are methicillin-susceptible (MSSA). During the early phase of MSSA BJI management national and international guidelines recommend the use of intra-venous type M penicillin with a dosage ranging from 100 to 200 mg/kg/day. Pharmacological properties of this class of penicillin require 4 to 6 infusions by day. Continuous infusion of beta-lactams is increasingly used especially in intensive care units. It allows an improvement of pharmacokinetic/pharmacodynamics (PK/PD) parameters and a reduction in time dedicated to infusion preparations by the nurses. However pharmacological data regarding such administration is required for type M penicillin. Design A 6-day, prospective, randomized, open-label, monocentric crossover study Participants Twelve adult patients with MSSA BJI Intervention Patients will be randomized in two groups: the first group will receive 3 days of cloxacillin (150 mg/kg/day) through 4 intermittent infusions/day followed by 3 days of cloxacillin (150 mg/kg/day) through continuous infusion (2 infusions during 12 hours). In the second group the infusion modalities will be inverted and continuous infusion will be preceded by a loading dose. Serum concentrations of cloxacillin will be determined at Day 3 and Days 6 The area under the curve / minimal inhibitory concentration ratio will be use to establish the equivalence between both administration modalities.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infection, Methicillin Susceptible Staphylococcus Aureus Infection, Cloxacillin Treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intermittent administration of cloxacillin
Arm Type
Active Comparator
Arm Title
continuous administration of cloxacillin
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Modification for administration mode of cloxacillin antibiotic
Intervention Description
For intermittent administration, patients will benefit from cloxacillin treatment in conventional hospitalization, in accordance with national guidelines, at a dose of 150 mg / kg per day in 4 infusions, not exceeding the maximum daily dose of 12 g / day according to. For continuous administration the same quantity of cloxacillin 150 mg / kg per day, without exceeding the maximum daily dose of 12 g / day, will be delivered by a self-propelled syringe in twice 12 hours. Patients randomly assigned to receive continuous administration will receive a dose of cloxacillin equivalent to the dose administered 4 times daily during iterative administration using a self-pulsating syringe. For the first day of the study, this loading dose will be subtracted from the 150 mg / kg dose to be administered continuously over the remaining 23 hours of the first day of the study and never exceed 12g / day. Pharmacological dosages will be performed on the third and sixth day in both arms
Primary Outcome Measure Information:
Title
The equivalence of the Pharmacokinetic-Pharmacodynamic indicators commonly used for the study of betalactamines: T> minimal inhibitory concentration
Time Frame
Six days
Title
The equivalence of the Pharmacokinetic-Pharmacodynamic indicators commonly used for the study of betalactamines: the area under the curve (AUC) / minimal inhibitory concentration
Time Frame
Six days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Staphylococcus aureus sensitive to methicillin and to be treated with cloxacillin by injectable antibiotic monotherapy For patients with Osteo-articular infection on material Presence of a fistula in contact with the prosthesis or implant. Pus in the joint or in contact with the prosthesis or implant Presence of at least 1 positive sample (1 sampling by articular puncture or 1 peroperative sampling or by blood culture) A histological analysis of the peri-prosthetic osteo-articular tissue which is the object of acute inflammation is a strong argument in favor of an Osteo-articular infection on material For spondylodiscitis Culture of a disco-vertebral biopsy puncture to isolate a methicillin sensitive S. aureus Positive haemocultures for S. aureus sensitive to methicillin with imaging examination (CT or MRI of the spine) showing images of spondylodiscitis For primitive arthritis : Culture of a positive methicillin-sensitive S. aureus articular fluid puncture Cultivation of a methicillin-sensitive S. aureus-positive surgical joint lavage fluid For osteitis the diagnosis is based on the following criterion: *Culture of surgical specimens from a focal zone of methicillin-sensitive S. aureus-positive osteitis Exclusion Criteria: Allergy to betalactamines Taking penicillin M within 36 hours before inclusion Renal function impaired with a glomerular filtration rate measured by MDRD formula of less than 30 ml / min Patient with renal function expected to change within 6 days of inclusion Hepatocellular insufficiency, whatever the degree -*Methotrexate intake Polytransfused (more than 2 CGR) in the previous week Patients requiring resuscitation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johan Johan, MD
Organizational Affiliation
Centre Hospitalier Universitaire de Nice
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU de Nice
City
Nice
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

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Pharmacological Comparison of Continuous and Intermittent Infusions of Cloxacillin

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