Pharmacological Comparison of Continuous and Intermittent Infusions of Cloxacillin

NCT ID: NCT03246360

Last Updated: 2019-04-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-23
• Study Completion Date: 2018-09-18

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.

Conditions

Infection; Methicillin Susceptible Staphylococcus Aureus Infection; Cloxacillin Treatment

Study Design

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

Study Groups

Intermittent administration of cloxacillin

Group Type: ACTIVE_COMPARATOR

Modification for administration mode of cloxacillin antibiotic

Intervention Type: DRUG

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

continuous administration of cloxacillin

Group Type: EXPERIMENTAL

Modification for administration mode of cloxacillin antibiotic

Intervention Type: DRUG

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

Interventions

Modification for administration mode of cloxacillin antibiotic

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

Intervention Type: DRUG

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

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

Sponsors

Centre Hospitalier Universitaire de Nice

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johan Johan, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire de Nice

Locations

CHU de Nice

Nice, , France

Countries

France

Other Identifiers

16-PP-04

Identifier Type: -

Identifier Source: org_study_id