RecruitingPhase 4NCT05681442
Beta-lactam Intermittent Versus Continuous Infusion and Combination Antibiotic Therapy in Sepsis
Sponsor
Assistance Publique - Hôpitaux de Paris
Enrollment
600 participants
Start Date
Nov 13, 2023
Study Type
INTERVENTIONAL
Conditions
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.
Eligibility
Min Age: 18 Years
Inclusion Criteria14
- 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
Exclusion Criteria22
- 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.
- 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)
Interventions
DRUGcontinuous pivotal βL-AB
continuous pivotal βL-AB
DRUGintermittent pivotal βL-AB
intermittent pivotal βL-AB (IID = control group)
DRUGAG infusion most 1 dose
AG infusion most 1 dose (AMT group )
DRUGAG infusion for 5 days
AG infusion for 5 days (ACT Group)
Locations(28)
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NCT05681442
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