Pharmacokinetics Study of Cefazolin in Hemodialysis (CEFAZODIAL)

NCT ID: NCT06093269

Last Updated: 2025-12-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-20
• Study Completion Date: 2025-12-31

Brief Summary

In chronic hemodialysis patients, bacteremia is most commonly caused by dialysis catheter infections. It is estimated that the vast majority (52-84%) of these infections are due to Gram-positive cocci, particularly Staphylococcus aureus (21-43%). Penicillin M (oxacillin and cloxacillin in France) is the reference beta-lactam for the treatment of invasive methicillin-sensitive S. aureus (MSSA) infections, but has not shown a prognostic benefit in large retrospective cohorts comparing penicillin M and cefazolin, at the expense of more frequent adverse events. Dosage in the chronic hemodialysis population is unclear because it is based on old studies.

Detailed Description

In chronic hemodialysis patients, bacteremia is most commonly caused by dialysis catheter infections. It is estimated that the vast majority (52-84%) of these infections are due to Gram-positive cocci, particularly Staphylococcus aureus (21-43%). The uremia associated with kidney replacement therapy affects the immune system as a whole and is associated with an increased risk of infection. Bacterial infections are a major cause of mortality and morbidity in these patients. They are a major cause of hospitalization and the third leading cause of death after cardiovascular disease and treatment discontinuation.

Penicillin M (oxacillin and cloxacillin in France) is the reference beta-lactam for the treatment of invasive methicillin-sensitive S. aureus (MSSA) infections, but large retrospective cohorts comparing penicillin M and cefazolin have shown no prognostic benefit at the expense of more frequent adverse events. What's more, its short half-life means that it requires a more time-consuming hemodialysis protocol. Cefazolin is therefore the preferred treatment for invasive MSSA infections in the target population. This is because its clearance is slow in chronic renal failure patients during the replacement phase, and it can be administered as a single dose during hemodialysis sessions. The most recent French recommendations for cefazolin plasma concentration targets are to maintain the free form concentration at more than 4 times the minimum inhibitory concentration (MIC) for documented invasive MSSA infections or 40 - 80 mg/L (total form) for probabilistic treatment.

However, the pharmacokinetics of cefazolin at these high doses have been little studied in renal failure and dialysis patients, and dosing recommendations are mainly based on the doses recommended in the Summary of Product Characteristics (500mg at each hemodialysis session) up to 2-3g according to later pharmacokinetic and efficacy studies, or a fairly similar dosage but adapted to the weight of each patient (20mg/kg).

To our knowledge, there are no pharmacokinetic studies in infected chronic hemodialysis patients using modern assessment tools. Given the high interest in this drug in the target population, it seems essential to conduct such a study. In a second phase, a larger study could be conducted to validate the doses proposed in this study.

Conditions

Hemodialysis Catheter Infection; Infection, Bacterial

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cefazolin

20mg/kg to be administered in the hemodialysis circuit at the end of the 4-hour dialysis period, with no dosage adjustment planned afterwards.

Group Type: EXPERIMENTAL

Blood samples

Intervention Type: BIOLOGICAL

For all subjects (short kinetics):

• Pre-injection of cefazolin
• Start of next dialysis
• Two hours after start of subsequent dialysis
• End of next dialysis, before cefazolin administration

Only in hospitalized subjects (rich kinetics):

• 30 minutes, 1h and 2h after cefazolin injection, to describe the cefazolin peak and possible post-dialysis rebound
• 12h, 24h and 36h after cefazolin injection, to better describe cefazolin elimination and distribution

Interventions

Blood samples

For all subjects (short kinetics):

• Pre-injection of cefazolin
• Start of next dialysis
• Two hours after start of subsequent dialysis
• End of next dialysis, before cefazolin administration

Only in hospitalized subjects (rich kinetics):

• 30 minutes, 1h and 2h after cefazolin injection, to describe the cefazolin peak and possible post-dialysis rebound
• 12h, 24h and 36h after cefazolin injection, to better describe cefazolin elimination and distribution

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Subjects aged 18 or over

2. On chronic intermittent dialysis

3. With a stated indication for initiation of cefazolin either:

1. For probabilistic treatment of a clinical presentation suggestive of MSSA infection

2. for treatment of Gram-positive cocci bacteremia

4. With the possibility of taking peripheral blood samples or samples from the dialysis machine until the next dialysis session at 48 hours.

5. Included within a maximum of one week after the first cefazolin injection.

6. Affiliated with French social security

7. Having signed an informed consent form

Exclusion Criteria

1. Pregnant or breast-feeding women

2. Dialysis lasting less than 3 hours, which most often corresponds to "acute" dialysis or the start of chronic dialysis, which fundamentally changes the elimination profile.

3. Allergy to cephalosporin and penicillin antibiotics (5-10% risk of cross-reactivity).

4. Non-anuric subjects with inhibitors of tubular creatinine secretion:

1. Curative-dose trimethoprim

2. Cimetidine

3. Ritonavir, Rilpivirine, Dolutegravir, Cobicistat

5. Subjects under guardianship, curatorship or safeguard of justice

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

Sponsors

University Hospital, Tours

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Valentin MAISONS, MD

Role: STUDY_DIRECTOR

University Hospital, Tours

Adrien LEMAIGNEN, MD-PhD

Role: STUDY_DIRECTOR

University Hospital, Tours

Locations

Department of hemodialysis, University Hospital of Tours

Orléans, , France

Department of hemodialysis, University Hospital of Tours

Tours, , France

Countries

France

Other Identifiers

EuCT number

Identifier Type: OTHER

Identifier Source: secondary_id

DR220268

Identifier Type: -

Identifier Source: org_study_id