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SepsisPhase 4BICCSNCT05681442

Beta-lactam Intermittent Versus Continuous Infusion and Combination Antibiotic Therapy in Sepsis

A Phase 4 study testing continuous pivotal βL-AB, intermittent pivotal βL-AB and AG infusion most 1 dose in people with Sepsis, run by Assistance Publique - Hôpitaux de Paris at 26 sites in France.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Sepsis
What is being tested?
continuous pivotal βL-AB, intermittent pivotal βL-AB and AG infusion most 1 dose
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
600 participants
Where
26 sitesFrance
Study dates
13 Nov 2023to 4 Mar 2027
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adults (≥ 18 years)
  • Hospital-acquired sepsis (according to sepsis 3.0 definitions) :
  • Patient hospitalized for more than 48 hours OR Patient discharged less than 48 hours ago
  • AND sepsis diagnosed within the last 24 hours
  • One of the following risk factors for gram negative multidrug resistant pathogens:
  • Prior intravenous antibiotic use within 7 days prior to sepsis onset with the exception of antibiotic effective only against Gram-positive bacteria, penicillin A and macrolides
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  • Prolonged hospital stay (≥ 15 days of hospitalization) within 3 months prior to sepsis onset Prolonged mechanical ventilation (≥ 5 days on mechanical ventilation) within 3 months prior to sepsis onset
  • Patients with indwelling devices (dialysis access lines, intravascular lines, urinary catheter, endotracheal or tracheostomy tube, gastrostomy or jejunostomy feeding tube)
  • Patients known to be infected, colonized or carriers of MDR gram negative bacteria within 3 months prior to sepsis onset
  • Exposure to an antibiotic (amoxicillin-clavulanic acid, C2G, C3G, fluoroquinolones) within 3 months prior to sepsis onset
  • A trip abroad to known geographical areas at risk (in particular the Indian subcontinent, South-East Asia, the Middle East and North Africa, the Mediterranean Basin) within 3 months prior to sepsis onset
  • A functional or organic abnormality of the urinary tract in case of urinary tract infection.
  • Appropriate bacteriological sampling performed before starting antimicrobial therapy
  • Expected stay in ICU of more than 3 days

Who cannot join

  • A priori known resistance to all the proposed beta-lactams or to amikacin
  • Need for extrarenal treatment at inclusion according to the criteria of Gaudry et al.
  • Known hypersensitivity to ceftazidime, piperacillin-tazobactam, cefepime, meropenem, ceftazidime-avibactam, ceftazolane-avibactam or to any of the excipients included in the corresponding pharmaceutical drugs,
  • Known hypersensitivity to any cephalosporin antibacterial agent,
  • Know hypersentitivity to any penem antibacterial agent,
  • Severe known hypersensitivity (eg, anaphylactic reaction, severe skin reaction) to any other beta-lactam antibiotic (eg, penicillins or monobactam ) or to any of its excipients.
Show all 22Show fewer
  • Known contraindication to the aminoglycoside family including
  • Hypersensitivity to the active substance, to any aminoglycoside antibacterial agent or to any of the excipients included in the corresponding pharmaceutical drugs,
  • Cirrhosis of grades B and C according to the Child-Pugh classification.
  • Myasthenia gravis.
  • Simultaneous administration of another aminoglycoside
  • Association with ataluren
  • Non-complicated urinary tract infection (corresponding to a positive ECBU not responsible for sepsis)
  • Bone marrow transplant or chemotherapy-induced neutropenia
  • Infections for which long-term antibiotic treatment > 8 days is strongly recommended (i.e., infective endocarditis, osteoarticular infections, anterior mediastinitis after cardiac surgery, hepatic or cerebral abscesses, chronic prostatitis for instance
  • Presence of antibiotic therapyfor the new sepsis before randomisation: (> 2 doses of antibiotics or > 16h for continuous infusion
  • Limitation of life support (comfort care applied only) at the time of screening
  • Enrolment to another interventional drug study
  • Pregnancy or breastfeeding
  • Subject deprived of freedom, subject under a legal protective measure
  • Non affiliation to any health insurance system
  • Refusal to participate to the study (patient or legal representative or family member or close relative if present)

Trial locations and contacts

26 sites in 1 country.

26 sites in 1 country

France26 sites

  • Réanimation polyvalente - CH d'Argenteuil - Hôpital Victor Dupuy

    Argenteuil, 95100

  • Réanimation polyvalente - CH Avignon

    Avignon, 84000

  • Médecine intensive - réanimation - CHU Bordeaux - Hôpital Pellegrin

    Bordeaux, 33000

  • Médecine intensive - réanimation - Ambroise Paré

    Boulogne-Billancourt, 92100

  • Médecine intensive - réanimation - CHU Gabriel Montpied

    Clermont-Ferrand, 63003

  • Anesthésie - Réanimation - Beaujon

    Clichy, 92110

  • Réanimation polyvalente/Surveillance continue - CH Sud Essonne-Etampes

    Étampes, 91150

  • Médecine intensive - réanimation-Centre Hospitalier Départemental Vendée

    La Roche-sur-Yon, 85000

  • Médecine intensive - réanimation - CHU Grenoble-Alpes Hôpital Michallon

    La Tronche, 38700

  • Réanimation polyvalente - CH de Versailles - Hôpital André Mignot

    Le Chesnay, 78150

  • Réanimation Médico Chirurgicale & USC - CH Le Mans

    Le Mans, 72037

  • Médecine Intensive Réanimation - Hôpital Croix Rousse

    Lyon, 69004

  • Médecine intensive - réanimation - HCL - Edouard Herriot

    Lyon, 69437

  • Réanimation polyvalente - CHR Metz-Thionville - Hôpital de Mercy

    Metz, 57085

  • Médecine intensive - réanimation - CHU Montpellier - Hôpital Lapeyronie

    Montpellier, 34295

  • Réanimation Chirurgicale - Saint Eloi

    Montpellier, 34295

  • Médecine Intensive Réanimation - Pasteur 2

    Nice, 06100

  • Médecine intensive - réanimation - CHU Nice - Hôpital Archet

    Nice, 06202

  • Médecine intensive - réanimation

    Orléans, 45000

  • Anesthésie - Réanimation - CHU Orléans

    Orléans, 86000

  • Médecine intensive et réanimation infectieuse - Bichat

    Paris, 75018

  • Réanimation chirurgicale - Bichat

    Paris, 75018

  • Institut Mutualiste du Montsouris

    Paris

  • Médecine intensive - réanimation - CHU Poitiers - Site de la Milétrie

    Poitiers, 86000

  • Médecine intensive - réanimation-CH St Denis - Hôpital Delafontaine

    Saint-Denis, 93200

  • Médecine intensive - réanimation - CHU de Strasbourg - Nouvel Hôpital Civil

    Strasbourg, 67091

Other trials in France

About this study

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.

Read the detailed description

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

  • Arm A: continuous infusion dosing of a pivotal βL-AB (Antibiotics) (CID group) AND AG (Aminoglycoside) infusion for 5 days (long duration) as appropriate combination therapy (ACT group)
  • Arm B: 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)
  • Arm C: continuous infusion dosing of a pivotal βL-AB (CID group) AND AG infusion at most 1 dose (AMT group)
  • Arm D: intermittent infusion dosing of a pivotal βL-AB (IID = group) AND AG infusion at most 1 dose (AMT group)

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.

Conditions
Sepsis
Being tested
continuous pivotal βL-AB, intermittent pivotal βL-AB, AG infusion most 1 dose, AG infusion for 5 days
Medical subject headings
Sepsis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • continuous pivotal βL-ABDrug

    Also called CID group

    continuous pivotal βL-AB

  • intermittent pivotal βL-ABDrug

    Also called IID control group

    intermittent pivotal βL-AB (IID = control group)

  • AG infusion most 1 doseDrug

    Also called AMT group

    AG infusion most 1 dose (AMT group )

  • AG infusion for 5 daysDrug

    Also called ACT Group

    AG infusion for 5 days (ACT Group)

Study groups in NCT05681442
Study groupRoleWhat they receive
continuous infusion dosing of a pivotal AND AG infusion for 5 daysExperimentalcontinuous infusion dosing of a pivotal βL-AB (CID group) AND AG infusion for 5 days (long duration) as appropriate combination therapy (ACT group)
Receives: Drug: continuous pivotal βL-AB; Drug: AG infusion for 5 days
intermittent infusion dosing of a pivotal βL-AB ND AG infusion for 5 daysExperimentalintermittent infusion dosing of a pivotal βL-AB (IID = control group) AND AG infusion for 5 days (long duration) as appropriate combination therapy (ACT = group)
Receives: Drug: intermittent pivotal βL-AB; Drug: AG infusion for 5 days
continuous infusion dosing of a pivotal βL-AB AND AG infusion at most 1 doseExperimentalcontinuous infusion dosing of a pivotal βL-AB (CID group) AND AG infusion at most 1 dose (AMT group )
Receives: Drug: continuous pivotal βL-AB; Drug: AG infusion most 1 dose
intermittent infusion dosing of a pivotal βL-AB AND AG infusion at most 1 doseExperimentalintermittent infusion dosing of a pivotal βL-AB (IID = group) AND AG infusion at most 1 dose (AMT group)
Receives: Drug: intermittent pivotal βL-AB; Drug: AG infusion most 1 dose

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: 30 days after acquiring sepsis

Secondary outcomes (16)

  1. 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;

    Measured: days 3,7and 30

  2. 30 day mortality in patient with proven Gram-negative infection

    Mortality rate at day 30 in patients with proven GNI

    Measured: 30 days after inclusion

  3. 30 day mortality in patient with proven non-fermentative GNI

    Mortality rate at day 30 in patients with proven non-fermentative GNI,

    Measured: 30 days after inclusion

  4. 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

    Measured: 30 days after inclusion

  5. 30-day mortality in patients that received non-carbapenem-βL

    Mortality rate at day 30 in patients that received non-carbapenem-βL

    Measured: 30 days after inclusion

  6. 30-day clinical recovery

    Clinical recovery at day 30 defined as admission clinical symptom resolved

    Measured: 30 days after inclusion

  7. 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

    Measured: 30 days after inclusion

  8. PK-PD (pharmacokinetic-pharmacodynamic) target attainment

    PK-PD target attainment rate evaluated as a dichotomous variable

    • 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

    Measured: at day 1, i.e. 24 hours after the loading dose and at day 3, i.e. 72 hours after the loading dose

  9. 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

    Measured: 30 min after the end of the first infusion dose (CMAX)

  10. 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

    Measured: 30 days after inclusion

  11. 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

    Measured: 7 days after inclusion

  12. 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

    Measured: 30 days after inclusion

  13. 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

    Measured: day 1 and day 30

  14. Length of ICU and hospital stays

    Length of ICU and hospital stays until day 30

    Measured: 30 days after inclusion

  15. 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

    Measured: 30 days after inclusion

  16. 180-day mortality

    Mortality rate at day 180

    Measured: 180 days after inclusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jan 2023
  2. Study start13 Nov 2023
  3. Primary completion4 Oct 2026
  4. Study completion4 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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
Masking
None (open label)
Enrolment
600 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05681442
Sponsor's protocol ID
APHP180596
Acronym
BICCS
Status last verified
Sep 2026
First submitted
21 Nov 2022
Last updated
16 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing continuous pivotal βL-AB, intermittent pivotal βL-AB and AG infusion most 1 dose in people with Sepsis, run by Assistance Publique - Hôpitaux de Paris at 26 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To compare the 30-day mortality of patients with hospital-acquired sepsis in the ICU (time frame: 30 days after acquiring sepsis). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05681442.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.

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