STRAtified Dosing based on Augmented renal clearance for CEFtriaxone in patients with severe community-acquired pneumonia: the STRADA-CEF trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UZ Leuven

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

18 Mar 2024 → ongoing

Decision date (initial)

2023-12-11

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

The Research Foundation – Flanders (FWO)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Dose response, Therapy, Pharmacokinetic, Pharmacodynamic

The general objective of this project is to evaluate the clinical benefit and safety of stratified every 24-hour (q24h) vs. q12h 2g ceftriaxone therapy in critically ill patients with sCAP based on the risk for development of ARC.

Secondary objectives 1

1. In a population PK and exposure-response analysis and PE analysis, the dose-exposure-(biomarker-)response-cost relationship of ceftriaxone will be investigated to provide more insights into the study results.

Conditions and MedDRA coding

Severe Community-Acquired Pneumonia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to – or within 72 hours after oral consent prior to – any screening procedures
2. Use of highly effective methods of birth control; defined as those that, alone or in combination, result in low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatment(s)) or commitment to a vasectomised partner.
3. Aged 18 years or older at the baseline visit
4. Confirmed diagnosis of sCAP, as defined by the current IDSA/ATS guideline
5. Ceftriaxone initiated for sCAP
6. (Planned) admission to an ICU ward

Exclusion criteria 14

1. Any disorder, which in the Investigator’s opinion might jeopardise the participant’s safety or compliance with the protocol
2. Patients expected to be discharged from the ICU within 48h
3. Patients expected to stop ceftriaxone therapy within 48h
4. Patients receiving palliative treatment under a “discontinue therapy" code
5. Previous enrolment in this study
6. Any prior or concomitant treatment(s) that might jeopardise the participant’s safety or that would compromise the integrity of the Trial
7. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate, highly effective contraceptive. A woman is considered of child-bearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
8. Participation in an interventional Trial with an investigational medicinal product (IMP) or device
9. Mildly to moderately decreased eGFRCKD-EPI (<80 mL/min/1.73m²) at baseline (max. 1 year prior to hospital admission)
10. Need for renal replacement therapy on the day of inclusion
11. Ceftriaxone treatment >12h before study enrolment
12. Patients with (suspicion of) meningitis, requiring treatment with ceftriaxone 2g q12h
13. Known hypersensitivity to beta-lactam antibiotics
14. Patients having received more than 1 amoxicillin-clavulanate dose since hospital admission

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Intensive care unit (ICU) Length of Stay (LOS)

Secondary endpoints 12

1. Delta SOFA score
2. ICU mortality
3. 28-day mortality
4. Hospital LOS
5. Alive ICU free days at day 28
6. Ventilator-free days at day 28
7. Clinical cure at day 14
8. Microbial eradication at day 14
9. Emergence of resistance at day 14
10. PK/PD target attainment
11. Assessment of safety
12. Procalcitonin and C-reactive protein concentrations

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

Sponsor organisation

UZ Leuven

Address

Herestraat 49

City

Leuven

Postcode

3000

Country

Belgium

Scientific contact point

Organisation

UZ Leuven

Contact name

Matthias Gijsen

Public contact point

Organisation

UZ Leuven

Contact name

Matthias Gijsen

Locations

1 EU/EEA country · 6 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 7 files

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

Application history

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