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

NCT05681442 | Recruiting Phase 4 DMC

• 1 other identifier: APHP180596
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 28

Brief 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. intermittent pivotal βL (Beta Lactamine) antibiotic infusion strategies and combination vs. monotherapy trial conducted with a 2X2 factorial design.

Conditions

Sepsis

Outcome Measures

Primary Outcomes (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).

  30 days after acquiring sepsis

Secondary Outcomes (16)

• New carriage, colonization or infection with one of the following BMR-GNB: at days 3, 7 and 30:

  days 3,7and 30

• 30 day mortality in patient with proven Gram-negative infection

  30 days after inclusion

• 30 day mortality in patient with proven non-fermentative GNI

  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).

  30 days after inclusion

• 30-day mortality in patients that received non-carbapenem-βL

  30 days after inclusion

Study Arms (4)

continuous infusion dosing of a pivotal AND AG infusion for 5 days

EXPERIMENTAL

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 ND AG infusion for 5 days

EXPERIMENTAL

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 AND AG infusion at most 1 dose

EXPERIMENTAL

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 AND AG infusion at most 1 dose

EXPERIMENTAL

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

Interventions

continuous pivotal βL-AB DRUG

continuous pivotal βL-AB

Also known as: CID group

continuous infusion dosing of a pivotal AND AG infusion for 5 days; continuous infusion dosing of a pivotal βL-AB AND AG infusion at most 1 dose

intermittent pivotal βL-AB DRUG

intermittent pivotal βL-AB (IID = control group)

Also known as: IID control group

intermittent infusion dosing of a pivotal βL-AB AND AG infusion at most 1 dose; intermittent infusion dosing of a pivotal βL-AB ND AG infusion for 5 days

AG infusion most 1 dose DRUG

AG infusion most 1 dose (AMT group )

Also known as: AMT group

continuous infusion dosing of a pivotal βL-AB AND AG infusion at most 1 dose; intermittent infusion dosing of a pivotal βL-AB AND AG infusion at most 1 dose

AG infusion for 5 days DRUG

AG infusion for 5 days (ACT Group)

Also known as: ACT Group

continuous infusion dosing of a pivotal AND AG infusion for 5 days; intermittent infusion dosing of a pivotal βL-AB ND AG infusion for 5 days

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• A priori known resistance to all the proposed beta-lactams or to amikacin
• 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.
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (28)

Médecine intensive - réanimation - CHU Amiens-Picardie

Amiens, 80054, France

WITHDRAWN

Réanimation polyvalente - CH d'Argenteuil - Hôpital Victor Dupuy

Argenteuil, 95100, France

RECRUITING

Réanimation polyvalente - CH Avignon

Avignon, 84000, France

RECRUITING

Médecine intensive - réanimation - CHU Bordeaux - Hôpital Pellegrin

Bordeaux, 33000, France

RECRUITING

Médecine intensive - réanimation - Ambroise Paré

Boulogne-Billancourt, 92100, France

RECRUITING

Médecine intensive - réanimation - CHU Gabriel Montpied

Clermont-Ferrand, 63003, France

RECRUITING

Anesthésie - Réanimation - Beaujon

Clichy, 92110, France

RECRUITING

Réanimation polyvalente/Surveillance continue - CH Sud Essonne-Etampes

Étampes, 91150, France

RECRUITING

Médecine intensive - réanimation-Centre Hospitalier Départemental Vendée

La Roche-sur-Yon, 85000, France

RECRUITING

Médecine intensive - réanimation - CHU Grenoble-Alpes Hôpital Michallon

La Tronche, 38700, France

RECRUITING

Réanimation polyvalente - CH de Versailles - Hôpital André Mignot

Le Chesnay, 78150, France

RECRUITING

Réanimation Médico Chirurgicale & USC - CH Le Mans

Le Mans, 72037, France

RECRUITING

Médecine Intensive Réanimation - Hôpital Croix Rousse

Lyon, 69004, France

RECRUITING

Médecine intensive - réanimation - HCL - Edouard Herriot

Lyon, 69437, France

RECRUITING

Réanimation polyvalente - CHR Metz-Thionville - Hôpital de Mercy

Metz, 57085, France

RECRUITING

Médecine intensive - réanimation - CHU Montpellier - Hôpital Lapeyronie

Montpellier, 34295, France

RECRUITING

Réanimation Chirurgicale - Saint Eloi

Montpellier, 34295, France

RECRUITING

Médecine Intensive Réanimation - Pasteur 2

Nice, 06100, France

RECRUITING

Médecine intensive - réanimation - CHU Nice - Hôpital Archet

Nice, 06202, France

RECRUITING

Médecine intensive - réanimation

Orléans, 45000, France

RECRUITING

Anesthésie - Réanimation - CHU Orléans

Orléans, 86000, France

RECRUITING

Médecine intensive et réanimation infectieuse - Bichat

Paris, 75018, France

RECRUITING

Réanimation chirurgicale - Bichat

Paris, 75018, France

RECRUITING

Institut Mutualiste du Montsouris

Paris, France

RECRUITING

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

Poitiers, 86000, France

RECRUITING

Médecine intensive et réanimation polyvalente 6 CHU de Reims - Hôpital Robert Debré

Reims, 51100, France

WITHDRAWN

Médecine intensive - réanimation-CH St Denis - Hôpital Delafontaine

Saint-Denis, 93200, France

RECRUITING

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

Strasbourg, 67091, France

RECRUITING

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Aline DECHANET

  Assistance Publique - Hôpitaux de Paris (AP-HP)

  STUDY CHAIR

Central Study Contacts

Jean-François TIMSIT, MD-PhD

CONTACT

01.40.25.77.07; jean-françois.timsit@aphp.fr

Lila BOUADMA, MD-PhD

CONTACT

01.40.25.77.07; lila.bouadma@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: November 21, 2022
• First Posted: January 12, 2023
• Study Start: November 13, 2023
• Primary Completion (Estimated): January 4, 2027
• Study Completion (Estimated): June 4, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (28)