A Phase 4 interventional study of continuous pivotal βL-AB and intermittent pivotal βL-AB in Sepsis, sponsored by Assistance Publique - Hôpitaux de Paris. Active, not recruiting at 26 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-11.
Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 4, Interventional, and Treatment
Patients hospitalized in ICU with sepsis (infection with life-threatening organ dysfunction according to sepsis 3.0 definitions) or septic shock presumably due to MDR-GNB (multidrug resistant Gram-negative bacteria). The study will be a prospective multicentre, randomized, open-label comparative continuous vs. intermittent pivotal βL (Beta Lactamine) antibiotic infusion strategies and combination vs. monotherapy trial conducted with a 2X2 factorial design.
The study will be a prospective multicentre, randomized, open-label comparative continuous vs. intermittent pivotal βL antibiotic infusion strategies and combination vs. monotherapy trial conducted with a 2X2 factorial design.
Patients will be randomized to one of four of the following treatment groups in a 1:1:1:1 ratio. Randomization will be stratified on the centre and the initial βL administered (meropenem versus other) to receive (i) βL antibiotic either as a continuous infusion: CID group or as intermittent infusion: IID group, and (ii) either at most 1 dose (short duration) : AMT group or 5 days (long duration) : ACT group of aminoglycoside
The primary objective of the study is to compare the 30-day mortality of patients with hospital-acquired sepsis in the ICU according to the mode of administration of the pivotal βL antibiotic (CID group vs. IID group).
The primary endpoint is the mortality rate at day 30 between CID and IID groups while the Co-primary objective is to compare the MAKE 30 (Major Adverse Kidney Events within 30 days) between patients that will receive an appropriate monotherapy with βL (AMT group) or an appropriate combination therapy with βL and 5 days of AG (ACT group).
moreover, The co-primary criterion is the percentage of patients with a MAKE 30, i.e. when patients met one of the following criteria within day 30: in-hospital mortality, receipt of renal replacement therapy (RRT) or persistent renal dysfunction (discharge serum creatinine/baseline serum creatinine ≥200%) between AMT and ACT groups.
1,899 studies on the registry are indexed under Sepsis; 462 are open to participants now.
This study's planned enrollment of 600 is above the median of 105 across 896 interventional studies indexed under Sepsis.
Browse Sepsis studies →Assistance Publique - Hôpitaux de Paris is the lead sponsor of 3,505 studies on the registry; 1,006 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Hospital-acquired sepsis (according to sepsis 3.0 definitions) :
One of the following risk factors for gram negative multidrug resistant pathogens:
Exclusion Criteria:
Known contraindication to the aminoglycoside family including
continuous infusion dosing of a pivotal βL-AB (CID group) AND AG infusion for 5 days (long duration) as appropriate combination therapy (ACT group)
Drug: continuous pivotal βL-AB · Drug: AG infusion for 5 days
intermittent infusion dosing of a pivotal βL-AB (IID = control group) AND AG infusion for 5 days (long duration) as appropriate combination therapy (ACT = group)
Drug: intermittent pivotal βL-AB · Drug: AG infusion for 5 days
continuous infusion dosing of a pivotal βL-AB (CID group) AND AG infusion at most 1 dose (AMT group )
Drug: continuous pivotal βL-AB · Drug: AG infusion most 1 dose
intermittent infusion dosing of a pivotal βL-AB (IID = group) AND AG infusion at most 1 dose (AMT group)
Drug: intermittent pivotal βL-AB · Drug: AG infusion most 1 dose
continuous pivotal βL-AB
Also known as: CID group
intermittent pivotal βL-AB (IID = control group)
Also known as: IID control group
AG infusion most 1 dose (AMT group )
Also known as: AMT group
AG infusion for 5 days (ACT Group)
Also known as: ACT Group
To compare the 30-day mortality of patients with hospital-acquired sepsis in the ICU
the primary objective is to compare the 30-day mortality of patients with hospital-acquired sepsis in the ICU according to the mode of administration of the pivotal βL antibiotic (CID group vs. IID group).
Time frame: 30 days after acquiring sepsis
New carriage, colonization or infection with one of the following BMR-GNB: at days 3, 7 and 30:
Percentage of patients with new carriage of MDR-GNB(taking into account all clinical samples and rectal surveillance swabs performed routinely each week),i.e one of the following ticarcillin-resistant Pseudomonas aeruginosa,Acinetobacter baumannii,or Stenotrophomonas maltophilia; extended-spectrum β-lactam-producing Entero bacteriaceae;high-concentration cephalosporinase producing AmpC Enterobacteriaceae;
Time frame: days 3,7and 30
30 day mortality in patient with proven Gram-negative infection
Mortality rate at day 30 in patients with proven GNI
Time frame: 30 days after inclusion
30 day mortality in patient with proven non-fermentative GNI
Mortality rate at day 30 in patients with proven non-fermentative GNI,
Time frame: 30 days after inclusion
30 day mortality in patient with proven GNI for which the minimum inhibitory concentration (MIC) of the βL used were higher to the breakpoints according to the European committee on Antimicrobial Susceptibility Testing (EUCAST).
Mortality rate at day 30 in patients with proven GNI for which the MIC of the βL used were higher to the accepted break-points
Time frame: 30 days after inclusion
30-day mortality in patients that received non-carbapenem-βL
Mortality rate at day 30 in patients that received non-carbapenem-βL
Time frame: 30 days after inclusion
30-day clinical recovery
Clinical recovery at day 30 defined as admission clinical symptom resolved
Time frame: 30 days after inclusion
30-day clinical recovery
Clinical recovery at day 30 defined as admission organ failures resolved with persistence of admission clinical symptoms and time to clinical recovery
Time frame: 30 days after inclusion
PK-PD (pharmacokinetic-pharmacodynamic) target attainment
PK-PD target attainment rate evaluated as a dichotomous variable o For βL (trough or plateau concentration according to randomization group), at day 1, i.e. 24 hours after the loading dose and at day 3, i.e. 72 hours after the loading dose § Target attainment scored "Yes" if measured drug concentration exceeded greater than four times to the causative pathogen MIC as 100% fT \> 4\*MIC
Time frame: at day 1, i.e. 24 hours after the loading dose and at day 3, i.e. 72 hours after the loading dose
PK-PD (pharmacokinetic-pharmacodynamic) target attainment
For AG, 30 min after the end of the first infusion dose (CMAX) § Target attainment scored "Yes" if measured drug concentration to causative pathogen MIC ratio is greater than 12 as CMAX/MIC \> 12
Time frame: 30 min after the end of the first infusion dose (CMAX)
Superinfection (primary infection site) or new infection (different infection site) at day 30 due to a GNB resistant to the βL administered at inclusion
Percentage of patients with superinfection or new nosocomial infection with GNB resistant to the βL administered at inclusion until day 30
Time frame: 30 days after inclusion
Microbiological failure persistence of the same microorganism at the same site at end-of-therapy (EOT) or within 7 days after EOT.
Percentage of patients for whom the microorganism is still recovered in bacterial culture from the initial infected site at EOT or within 7 days after EOT
Time frame: 7 days after inclusion
New carriage, colonization or infection with Pseudomonas aeruginosa not susceptible to the βL administered at days 3, 7 and 30
Percentage of patients with new carriage colonization or infection with Pseudomonas aeruginosa not susceptible to the βL administered until day 30
Time frame: 30 days after inclusion
Duration of organ failure between day 1 and day 30
Organ failures assessed by AUCSOFA and its organ components measured between day 1 and day 30
Time frame: day 1 and day 30
Length of ICU and hospital stays
Length of ICU and hospital stays until day 30
Time frame: 30 days after inclusion
Occurrence of adverse events at day 30
Percentage of patients with encephalopathy (delay between inclusion and 2 RASS scores = -1 in a row) or renal failure at discharge (RRT or persistent renal dysfunction) until day 30
Time frame: 30 days after inclusion
180-day mortality
Mortality rate at day 180
Time frame: 180 days after inclusion
Plan to share: No
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Assistance Publique - Hôpitaux de Paris