ASTARTÉ: Temocillin vs Meropenem for the Targeted Treatment of Bacteraemia Resistant to Third Gen Cephalosporins

Sponsor

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla (Other)

Overall Status

Recruiting

CT.gov ID

NCT04478721

Collaborator

Spanish Network for Research in Infectious Diseases (Other), SCReN Spanish research Network- CTU-HUVR (Other)

334

Enrollment

Locations

Arms

32.5

Anticipated Duration (Months)

10.4

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Phase 3, Multicenter, Randomised, Controlled, Open-Label Study to demonstrate noninferiority of temocillin (unauthorized investigational medicinal product IMP in Spain, but authorized in Belgium and UK) vs a carbapenem antibiotic (meropenem) in adults with bacteraemia due to third-generation cephalosporin-resistant Enterobacteriaceae.

The duration of treatment will be between 7 and 14 days. From the 5th day of intravenous treatment, the sequential oral treatment is permitted if the patient meets appropriate conditions.

Condition or Disease	Intervention/Treatment	Phase
Bacteremia	Drug: Temocillin Drug: Meropenem	Phase 3

Detailed Description

The objective of the trial is to demonstrate the non-inferiority of temocillin (2g each 8 hours, intravenous) to carbapenems (meropenem 1g each 8 hours, intravenous) in terms of efficacy and safety in the targeted treatment of bacteraemia due to Enterobacteriaceae resistant to third-generation cephalosporins, and therefore provide evidence for the use of temocillin in these infections.

The duration of treatment will be between 7 and 14 days. From the 5th day of intravenous treatment, the sequential oral treatment is permitted if the patient meets appropriate conditions.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

334 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized 1.1 to temocillin: meropenemRandomized 1.1 to temocillin: meropenem

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomised Controlled Trial of Temocillin vs Meropenem for the Targeted Treatment of Bacteraemia Due to Enterobacteriaceae Showing Resistance to Third Generation Cephalosporins

Actual Study Start Date :

Dec 15, 2020

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Temocillin Patients enrolled in this arm, will receive 2g each 8 hours of intravenous temocillin.	Drug: Temocillin The intervention of experimental arm will be Intravenous administration of temocillin.
Active Comparator: Meropenem Patients enrolled in this arm, will receive 1g each 8 hours of intravenous meropenem.	Drug: Meropenem The intervention of comparator arm will be intravenous administration of meropenem.

Arm

Intervention/Treatment

Experimental: Temocillin

Patients enrolled in this arm, will receive 2g each 8 hours of intravenous temocillin.

Drug: Temocillin

The intervention of experimental arm will be Intravenous administration of temocillin.

Active Comparator: Meropenem

Patients enrolled in this arm, will receive 1g each 8 hours of intravenous meropenem.

Drug: Meropenem

The intervention of comparator arm will be intravenous administration of meropenem.

Outcome Measures

Primary Outcome Measures

Number of participants with a "success" at the test of cure (TOC) [Up to 7-10 days after the last day of antibiotic therapy]
A success at the test of cure is the resolution of infection symptoms
Survival at day 28 [At day 28.]
Number of patients who are alive
Number of patients who do not need to stop or change the assigned drug [Up to 7-14 days after the last day of antibiotic therapy]
Reasons for not change can be no adverse event, no perceived failure during treatment or no occurrence of a superimposed infection. Participants who stop or change the assigned drug will not meet the primary outcome.
Number of patients who do not need to prolong therapy beyond 14 days [Up to 7-14 days after the last day of antibiotic therapy]
Assigned treatment to be administered for less than 14 days
Not recurrence until day 28 [At day 28.]
Recurrence is reappearance of symptoms with positive blood culture for the same microorganism. Participants with recurrence will not meet the primary outcome.

Secondary Outcome Measures

28-day mortality [Up to day 28.]
Number of patients dead up to day 28.
Length of hospital stay (days) [Through study completion, an average of 28 days]
Number of days patients has been in-hospital
Length of intravenous therapy (days) [From day 1 of intravenous antibiotic treatment administration to last intravenous administration, average 14 days]
Number of days patients has been under intravenous antibiotic treatment
Length of total administration of therapy (days) [From day 1 of intravenous or oral antibiotic treatment administration to last intravenous or oral administration, average 14 days]
Number of days patients has been under intravenous or oral antibiotic treatment
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [Up to day 28]
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Number of subjects with resistance development during therapy [Up to day 28]
Resistance development will be measured in a positive blood culture
Recurrence rate [Up to day 28.]
Percentage of subjects with recurrence
Changes in Sequential Organ failure (SOFA) score [At days 1, 3, end of treatment (days 7-14) and visit 4]
Sequential Organ failure (SOFA) score changes
Changes in Barthel Index for Activities of Daily Living (ADL) for patients older than 70 years old [At days 1, 3, end of treatment (days 7-14) and visit 4]
Barthel Index for Activities of Daily Living (ADL) score changes; score from 0, completely dependent patient to 100, completely independent for activities of daily living

Other Outcome Measures

Peak Plasma Concentration (Cmax) of temocillin [At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3]
Exploratory objective in a reduced number of patients on which plasma levels of temocillin will be measured to determine maximum plasma levels of temocillin
Minimum Plasma Concentration (Cmin) of temocillin [At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3]
Exploratory objective in a reduced number of patients on which plasma levels of temocillin will be measured to determine minimum plasma levels of temocillin
Area under the plasma concentration versus time curve (AUC) of temocillin [At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3]
Exploratory objective in a reduced number of patients on which plasma levels of temocillin will be measured to determine area under curve of temocillin

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patients with monomicrobial bacteraemia due to Enterobacteriaceae showing resistance to cefotaxime, ceftriaxone (MIC >2 mg/L) and/or ceftazidime (MIC >4 mg/L), ands sensible to temocillin (MIC ≤8 mg/L) and meropenem (MIC ≤2 mg/L).
Duration of intravenous treatment is planned to be at least 4 days.
The patient signed informed consent form.

Exclusion Criteria:

<18 years
Pregnancy
Breastfeeding
Palliative care
Allergy to betalactams
Polymicrobial bacteraemia
Meningitis
Infections typically needing prolonged >14 days of therapy (e.g., endocarditis, prosthetic joint infection, vascular graft infection, empyema, chronic prostatitis)
Severe neutropenia
Shock
Active empirical treatment> 96 hours after initial blood culture extraction

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Clínico Universitario de Santiago	Santiago de Compostela	A Coruña	Spain	15706
2	Hospital ParcTaulí	Sabadell	Barcelona	Spain	08208
3	Hospital Universitario Mútua Terrassa	Terrassa	Barcelona	Spain	08221
4	Hospital Marqués de Valdecilla	Santander	Cantabria	Spain	39008
5	Hospital Universitario de Jerez de la Frontera	Jerez de la Frontera	Cádiz	Spain	11407
6	Hospital Universitario de Puerto Real	Puerto Real	Cádiz	Spain	11510
7	Complejo Hospitalario San Millán-San Pedro De La Rioja	Autol	La Rioja	Spain	26560
8	Complejo Hospitalario de Navarra	Pamplona	Navarra	Spain	31008
9	Complejo Hospitalario Universitario La Coruña	A Coruña		Spain	15006
10	Hospital General Universitario de Alicante	Alicante		Spain	03010
11	Hospital Universitario Torrecárdenas	Almería		Spain	04009
12	Hospital del Mar	Barcelona		Spain	08003
13	Hospital Clínic de Barcelona	Barcelona		Spain	08036
14	Hospital Sant Pau	Barcelona		Spain	08041
15	Hospital Universitario Reina Sofía	Córdoba		Spain	14004
16	Hospital Universitario Virgen de las Nieves	Granada		Spain	18014
17	Hospital Universitario Clínico San Cecilio	Granada		Spain	18016
18	Hospital Universitario Juan Ramón Jiménez	Huelva		Spain	21005
19	Complejo Hospitalario de Jaén	Jaén		Spain	23007
20	Hospital Universitario Locus Augusti, Lugo	Lugo		Spain	27003
21	Hospital Universitario de la Princesa	Madrid		Spain	28006
22	Hospital General Universitario Gregorio Marañón	Madrid		Spain	28007
23	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
24	Hospital Universitario La Paz	Madrid		Spain	28046
25	Hospital Regional de Málaga	Málaga		Spain	29010
26	Hospital Universitario Virgen de la Victoria	Málaga		Spain	29010
27	Hospital Universitari Son Espases	Palma		Spain	07120
28	Hospital Universitario Virgen Macarena	Sevilla		Spain	41009
29	Hospital Universitario Virgen del Rocío	Sevilla		Spain	41013
30	Hospital Universitario Virgen de Valme	Sevilla		Spain	41014
31	Complejo Hospitalario Universitario de Vigo	Vigo		Spain	36313
32	Hospital Clínico Universitario Lozano Blesa	Zaragoza		Spain	50009