Pharmacokinetics study of Cefazolin in haemodialysis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Regional Universitaire De Tours

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12], Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

20 Nov 2023 → 24 Dec 2025

Decision date (initial)

2023-10-05

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

CHRU de Tours

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic

Description of the pharmacokinetics of cefazolin in chronic haemodialysis patients with infections, as part of routine care.

Secondary objectives 4

1. Evaluation of the safety profile of cefazolin (within 6 weeks of the last dose)
2. Evaluation of the link between dosage and clinical efficacy (early and late)
3. Identification of factors predictive of under/over exposure to cefazolin
4. Suggest dosage regimens to optimise exposure to cefazolin.

Conditions and MedDRA coding

Chronic haemodialysis patients suffering from infection.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Subjects aged 18 years 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 SAMS infection 2/ For treatment of Gram-positive cocci bacteremia
4. With the possibility of taking peripheral blood samples or blood samples from the dialysis machine until the next dialysis session at 48 hours
5. Covered by or entitled to social security
6. Signed informed consent form

Exclusion criteria 5

1. Pregnant or breastfeeding woman
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: Curative-dose trimethoprim, Cimetidine, Ritonavir, Rilpivirine, Dolutegravir, Cobicistat
5. Patient following any measures of legal presentation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time during which the plasma concentration of cefazolin is greater than the target concentration of 40 mg/L.

Secondary endpoints 5

1. Occurrence of adverse events (within 6 weeks of last dose)
2. Early clinical efficacy (at 1 week from start of treatment) in cefazolin-susceptible patients, defined as freedom from failure, composite endpoint including: 1/ Persistence of fever >38°C 2/ Persistence of positive blood cultures for the same germ(s) 3/ Death for infectious reasons 4/ Change of antibiotic therapy due to ineffectiveness
3. Late clinical efficacy (at 6 weeks from the start of treatment) in patients with cefazolin-susceptible organisms, defined as absence of failure, composite criterion including : 1/ Persistence of positive blood cultures 2/ Recurrence of initial infection 3/ Death due to infection 4/ Change of antibiotic therapy due to ineffectiveness
4. Each of the criteria of the 2 composite scores taken in isolation
5. Association of pharmacokinetic variability factors (covariates) with the occurrence of under- or over-exposure (concentration below 40mg/L or above 80mg/L)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Regional Universitaire De Tours

Sponsor organisation

Centre Hospitalier Regional Universitaire De Tours

Address

2 Boulevard Tonnelle

City

Tours

Postcode

37000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Regional Universitaire De Tours

Contact name

Coordinating Investigator

Public contact point

Organisation

Centre Hospitalier Regional Universitaire De Tours

Contact name

Coordinating Investigator

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications