Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT06093269

Pharmacokinetics Study of Cefazolin in Hemodialysis (CEFAZODIAL)

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Notify Me

Key information

Conditions

Hemodialysis Catheter Infection Bacterial Infections Bacterial Infections and Mycoses Infection, Bacterial Infections

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Department of hemodialysis, University Hospital of Tours, Orléans, France

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Subjects aged 18 or over
  • On chronic intermittent dialysis
  • With a stated indication for initiation of cefazolin either:
  • For probabilistic treatment of a clinical presentation suggestive of MSSA infection
  • for treatment of Gram-positive cocci bacteremia
  • With the possibility of taking peripheral blood samples or samples from the dialysis machine until the next dialysis session at 48 hours.
  • Included within a maximum of one week after the first cefazolin injection.
  • Affiliated with French social security
  • Having signed an informed consent form

Exclusion criteria

  • Pregnant or breast-feeding women
  • 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.
  • Allergy to cephalosporin and penicillin antibiotics (5-10% risk of cross-reactivity).
  • Non-anuric subjects with inhibitors of tubular creatinine secretion:
  • Curative-dose trimethoprim
  • Cimetidine
  • Ritonavir, Rilpivirine, Dolutegravir, Cobicistat
  • Subjects under guardianship, curatorship or safeguard of justice

Treatment and study plan

blood samples

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

Primary outcomes

  1. Time during which cefazolin plasma concentration exceeds the target concentration of 40 mg/L.

    Time frame: 48 hours after injection

Secondary outcomes

  1. Occurrence of adverse events

    Time frame: Within 6 weeks of last dose

  2. Early clinical efficacy - Persistence of fever >38°C

    Time frame: At 1 week from start of treatment

    Early clinical efficacy (at 1 week from start of treatment) in cefazolin-susceptible patients, defined as absence of failure, composite endpoint including:

    • Persistence of fever >38°C
    • Persistence of positive blood cultures for the same germ(s)
    • Death for infectious reasons
    • Change of antibiotic therapy due to ineffectiveness

  3. Early clinical efficacy - Persistence of positive blood cultures for the same germ(s)

    Time frame: At 1 week from start of treatment

    Early clinical efficacy (at 1 week from start of treatment) in cefazolin-susceptible patients, defined as absence of failure, composite endpoint including:

    • Persistence of fever >38°C
    • Persistence of positive blood cultures for the same germ(s)
    • Death for infectious reasons
    • Change of antibiotic therapy due to ineffectiveness

  4. Early clinical efficacy - Death for infectious reasons

    Time frame: At 1 week from start of treatment

    Early clinical efficacy (at 1 week from start of treatment) in cefazolin-susceptible patients, defined as absence of failure, composite endpoint including:

    • Persistence of fever >38°C
    • Persistence of positive blood cultures for the same germ(s)
    • Death for infectious reasons
    • Change of antibiotic therapy due to ineffectiveness

  5. Early clinical efficacy - Change of antibiotic therapy due to ineffectiveness

    Time frame: At 1 week from start of treatment

    Early clinical efficacy (at 1 week from start of treatment) in cefazolin-susceptible patients, defined as absence of failure, composite endpoint including:

    • Persistence of fever >38°C
    • Persistence of positive blood cultures for the same germ(s)
    • Death for infectious reasons
    • Change of antibiotic therapy due to ineffectiveness

  6. Late clinical efficacy - Persistence of positive blood cultures

    Time frame: At 6 weeks from the start of treatment

    Late clinical efficacy (at 6 weeks from the start of treatment) in patients with cefazolin-susceptible organisms, defined as absence of failure, composite endpoint including :

    • Persistence of positive blood cultures
    • Recurrence of initial infection
    • Infectious death
    • Change of antibiotic therapy due to ineffectiveness

  7. Late clinical efficacy - Recurrence of initial infection

    Time frame: At 6 weeks from the start of treatment

    Late clinical efficacy (at 6 weeks from the start of treatment) in patients with cefazolin-susceptible organisms, defined as absence of failure, composite endpoint including :

    • Persistence of positive blood cultures
    • Recurrence of initial infection
    • Infectious death
    • Change of antibiotic therapy due to ineffectiveness

  8. Late clinical efficacy - Infectious death

    Time frame: At 6 weeks from the start of treatment

    Late clinical efficacy (at 6 weeks from the start of treatment) in patients with cefazolin-susceptible organisms, defined as absence of failure, composite endpoint including :

    • Persistence of positive blood cultures
    • Recurrence of initial infection
    • Infectious death
    • Change of antibiotic therapy due to ineffectiveness

  9. Late clinical efficacy - Change of antibiotic therapy due to ineffectiveness

    Time frame: At 6 weeks from the start of treatment

    Late clinical efficacy (at 6 weeks from the start of treatment) in patients with cefazolin-susceptible organisms, defined as absence of failure, composite endpoint including :

    • Persistence of positive blood cultures
    • Recurrence of initial infection
    • Infectious death
    • Change of antibiotic therapy due to ineffectiveness

  10. Persistence of fever >38°C

    Time frame: At 1 week from start of treatment

    All components of the composite endpoint "Early clinical efficacy" will be assessed separately.

  11. Persistence of positive blood cultures for the same germ(s)

    Time frame: At 1 week from start of treatment

    All components of the composite endpoint "Early clinical efficacy" will be assessed separately.

  12. Death for infectious reasons

    Time frame: At 1 week from start of treatment

    All components of the composite endpoint "Early clinical efficacy" will be assessed separately.

  13. Change of antibiotic therapy due to ineffectiveness

    Time frame: At 1 week from start of treatment

    All components of the composite endpoint "Early clinical efficacy" will be assessed separately.

  14. Persistence of positive blood cultures

    Time frame: At 6 weeks from the start of treatment

    All components of the composite endpoint "Late clinical efficacy" will be assessed separately.

  15. Recurrence of initial infection

    Time frame: At 6 weeks from the start of treatment

    All components of the composite endpoint "Late clinical efficacy" will be assessed separately.

  16. Infectious death

    Time frame: At 6 weeks from the start of treatment

    All components of the composite endpoint "Late clinical efficacy" will be assessed separately.

  17. Change of antibiotic therapy due to ineffectiveness

    Time frame: At 6 weeks from the start of treatment

    All components of the composite endpoint "Late clinical efficacy" will be assessed separately.

  18. Characterizing the pharmacokinetic variability of Cefazolin

    Time frame: 48 hours after injection

    Characterizing the pharmacokinetic variability of Cefazolin with the occurrence of under- or over-exposure (concentration below 40 mg/L or above 80mg/L)

Sponsors and collaborators

Lead sponsor

University Hospital, Tours

Other

Registry information

Acronym: CEFAZODIAL

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Oct 23, 2023
Registry last updated
Dec 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.