Temocilin vs meropenem for the treatment of infections due to Enterobacteriales

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

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

21 May 2024 → 26 Dec 2024

Decision date (initial)

2024-05-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Instituto de Salud Carlos III

External identifiers

EU CT number

2023-508440-21-00

EudraCT number

2020-000064-39

ClinicalTrials.gov

NCT04478721

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To demonstrate the non-inferiority of temocillin to carbapenems in terms of efficacy and safety in the targeted treatment of bacteraemia due to Enterobacterales resistant to third-generation cephalosporins, and therefore provide evidence for the use of temocillin in these infections.

Secondary objectives 3

1. (a) To provide specific information about the efficacy and safety of temocillin and carbapenems for the targeted infection in subgroups of patients usually excluded from randomised trials (namely, severely ill patients, elderly, immunocompromised and patients with renal insufficiency).
2. (b) To provide further information about the pharmacokinetics and pharmacodynamics of temocillin.
3. (c) To provide information about the MIC of temocillin of Enterobacterales resistant to third-generation cephalosporins according to the mechanisms of resistance.

Conditions and MedDRA coding

Infections due to Enterobacteriaceae

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Hospitalized adult patients (18 years or older) who present bacteremia of any origin with monomicrobial isolation of Enterobacterales in blood culture; Patients with polymicrobial bacteremia caused by more than one enterobacteria may also be included, with at least one of them being resistant to third-generation cephalosporins (see next point), and both being sensitive to meropenem and temocillin.
2. The microorganism is resistant to third generation cephalosporins: cefotaxime, ceftriaxone (MIC > 2 mg/L) and/or ceftazidime (MIC > 4 mg/L).
3. The microorganism is sensitive to temocillin (MIC ≤8 mg/L, except in bacteremia of urinary origin only, for which the criterion is MIC ≤16 mg/L) and meropenem (MIC ≤2 mg/L).
4. Patients in whom, once diagnosed with potentially includable Enterobacterales bacteremia, the need to maintain intravenous treatment is estimated for at least 4 days from randomization, or 3 days if empirical treatment prior to randomization was appropriate.
5. Patients who have signed the informed consent.
6. Potentially fertile patients must have a negative pregnancy test.

Exclusion criteria 9

1. Minors under 18 years of age.
2. Terminal situation, or estimated life expectancy of less than 30 days, or under purely palliative treatment for their underlying illness, so that necessary actions will not be taken to control the focus of infection if necessary. Patients in palliative care and with a life expectancy greater than 30 days may be included, in which control of the focus is not necessary or, if necessary, will be carried out.
3. Pregnant or breastfeeding women.
4. Known allergy or hypersensitivity to beta-lactams
5. Polymicrobial bacteremia (except when the other microorganism is considered a contaminant, such as coagulase-negative staphylococci or diphtheroids in a single extraction, or in the case of isolation of more than one enterobacteria, provided that the criterion that at least one of them is resistant to third generation cephalosporins, and both sensitive to meropenem and temocillin).
6. Delay in inclusion greater than 48 hours after having the antibiotic sensitivity data of the Enterobacteriaceae isolated in blood culture, or who have received active empirical treatment for more than 96 hours after the initial blood culture was obtained.
7. Infections that typically have a recommended treatment duration of more than 14 days (endocarditis, osteomyelitis, prosthetic infection, chronic prostatitis, empyema...), or meningitis. Patients who initially do not have a confirmed diagnosis of these infections may be included; If their diagnosis is made later, the patient may be kept in the trial at the discretion of the researcher, establishing the duration of treatment that is considered necessary.
8. Peritoneal dialysis or continuous hemofiltration.
9. Patients who are participating in another clinical trial with active treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. A composite endpoint "success" will be used, including: (a) clinical success at test of cure (TOC); (b) alive at day 28; (c) no need to stop or change the assigned drug because of adverse event, perceived failure during treatment or occurrence of a superimposed infection; (d) no need to prolong therapy beyond 14 days; (e) Absence of recurrence up to day 28.

Secondary endpoints 10

1. 28-day mortality
2. Length of hospital stay and therapy (IV and total)
3. Appearance of adverse events (frequency and severity).
4. Resistance development during therapy
5. Development of superimposed infections.
6. Recurrence rate (recurrences and reinfections) until day 28.
7. Change in SOFA score
8. In patients over 70 years of age: changes in the Barthel scales
9. Exploratory variables (carried out only at the coordinating center): serum temocillin levels, temocillin MIC in Enterobacterales according to resistance mechanisms to third-generation cephalosporins.
10. Exposure variables: age, sex, Charlson, underlying chronic conditions, type of acquisition, presence of venous and urinary catheters, mechanical ventilation, surgery previous month, bacteremia focus, Pitt score, presence of sepsis, SOFA prior to initiation of study treatment, mortality risk scale INCREMENT ESBL, empirical therapy (active in vitro or not), hours until administration of first active drug, hours until administration of first study drug, focus control and support therapy.

Investigational products

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

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Sponsor organisation

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Address

Avenida De Manuel Siurot S/n

City

Sevilla

Postcode

41013

Country

Spain

Scientific contact point

Organisation

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Contact name

Unidad de Investigación Clínica y ensayos clínicos UICEC HUVR

Public contact point

Organisation

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Contact name

Unidad de Investigación Clínica y ensayos clínicos UICEC HUVR

Locations

1 EU/EEA country · 30 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 10 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