Beta-Lactams Dosing In Pneumonia in ICU in Patients Treated by Continuous Renal Replacement Therapy: the BLIPIC Study

Pneumonia Clinical Trial

— BLIPIC  

Official title:

Beta-Lactams Dosing In Pneumonia in ICU in Patients Treated by Continuous Renal Replacement Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03897582
• Other study ID #: 2018-05
• Status: Recruiting
• Start date: February 22, 2019
• Est. completion date: May 31, 2026

Study information

• Verified date: February 2024
• Source: Centre Hospitalier de Valenciennes
• Contact: Fabien Lambiotte, MD
• Phone: + 33 3 27 14 33 33
• Email: lambiotte-f[@]ch-valenciennes.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Pneumonia are the most frequent infections in ICU. Little is known about beta-lactam doses necessary for this infection for patients treated with continuous veino-veinous hemodialysis. The pharmacokinetic variability expose to over and underdosage leading to toxicity or therapeutic failure. The aim of this study is to define if beta-lactams doses used in pneumonia for patients with acute kidney injury treated with our hemodialysis conditions lead to beta-lactam therapeutic plasma levels.

Description:

Pneumonia are the most frequent infections in ICU. Little is known about beta-lactam doses necessary for this infection for patients treated with continuous veino-veinous hemodialysis. The pharmacokinetic variability expose to over and underdosage leading to toxicity or therapeutic failure. The aim of this study is to define if beta-lactams doses used in pneumonia for patients with acute kidney injury treated with our hemodialysis conditions lead to beta-lactam therapeutic plasma levels. This prospective observational multicenter study will include all patients with pneumonia treated by beta-lactam and continuous veino-veinous hemodialysis in 5 ICU. Blood sampling will be done at assumed pharmacokinetic steady state. Protocol sample concentrations of beta-lactams immediately prior to re-dosing, after 24 hours of association of intraveinous beta-lactam and continuous veino-veinous hemodialysis. Another sample will be done after 48 hours. The ICU measured bacterial MICs routinely when the pathogen will be determined. Surveyed ICUs will adopt SFM-EUCAST breakpoints for the targeted (or suspected) bacteria to determine pharmacokinetic/pharmacodynamic targets when a mesured MIC (Minimum inhibitory concentration) is not available. Local hospital antibiogram data can also be used to describe likely pathogen susceptibility. Target attainment is defined as 100% fT> 5 MIC. Due to the long delay to receive therapeutic drug monitoring results, doses could not be ajusted. Factors which could cause concentrations variations will be registered. When neurotoxicity is suspected, a sample will be realized to know beta-lactam concentration and the adverse event will be notified.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 65
• Est. completion date: May 31, 2026
• Est. primary completion date: May 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Aged = 18 years
• Receiving intraveinous beta-lactam : amoxicillin, amoxicillin-clavulanic acid, piperacillin-tazobactam, cefotaxime, ceftazidime, cefepime, meropenem, imipenem
• With AKI defined as any of the following, and treated with Multifiltrate Ci-Ca CVVHD

1000® kit with a dialysis dose of 25 ml/kg/h :

• Increase in creatininemia = 0.3 mg/dl (= 26.5 µmol/l) within 48 hours
• Increase in creatininemia = 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days
• Urine volume < 0.5 ml/kg/h for 6 hours
• Hospitalized in ICU
• Presence of a catheter to facilitate sample collection
• With pneumonia defined as any of the following :
• Chest X-ray pneumonia : opacities, new or progressive infiltrates
• AND at least one of the following : hyperthermia > 38°C or hypothermia < 36°C with no other explanation ; leukopenia < 4 G/L ou leukocytosis > 12G/L
• AND at least one of the following : new onset purulent sputum or change in sputum character, new onset or worsening cough or dyspnea or tachypnea, rales or bronchial breathing, lower oxygen saturation/hypoxemia or increase of oxygen needs or respiratory assistance
• Treated within 24 hours by citrate hemodialysis AND beta-lactam respecting dose and

administration conditions of the study :

• Amoxicillin : loading dose followed immediately by 2g by extended infusion for 4 hours every 8 hours
• Amoxicillin-clavulanic acid : 2g every 8 hours by intermittent bolus
• Piperacillin-tazobactam: loading dose followed immediately by 4g/0.5g by continuous infusion every 8 hours (< 80 kg) ou 6 hours (> 80 kg)
• Cefotaxime: loading dose followed immediately by 2g by continuous infusion every 8 hours Ceftazidime : loading dose followed immediately by 2g by continuous infusion every 8 hours
• Cefepime: loading dose followed immediately by 2g by continuous infusion every 8 hours
• Meropenem : loading dose followed immediately by 2g (> 60 kg) ou 1,33g (< 60 kg) by extended infusion for 4 hours every 8 hours
• Imipenem : loading dose followed immediately by 750 mg (< 80 kg) ou 1g (> 80 kg) by extended infusion for 4 hours every 6 hours In case of extrem weight, dose will be on investigator's discretion but administration conditions have be to respected.
• No objection has been obtained from the patient or their legally authorised representative

Exclusion Criteria:

• Aged < 18 years
• ECMO
• Cystic fibrosis
• Burn victim
• Pregnant woman
• Any rapidly-progressing disease or immediately life-threatening illness
• Objection from the patients or their legally authorised representative
• No social security scheme
• Interruption of antibiotic before samples
• Patient in prison

Related Conditions & MeSH terms

• Antibiotic
• Beta-lactam
• Continuous Renal Replacement Therapy
• Pneumonia

Locations

Country	Name	City	State
France	Centre Hospitalier de Valenciennes	Valenciennes	Nord

Sponsors (6)

Lead Sponsor	Collaborator
Centre Hospitalier de Valenciennes	Centre Hospitalier de Bethune, Centre hospitalier de Boulogne, Centre Hospitalier de Lens, General Hospital of Douai, University Hospital, Lille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of beta-lactams concentrations above plasma therapeutic levels	We aimed to obtain concentrations over 5 MIC (Minimum inhibitory concentration) for at least 80% of patients.	Day 3 after start of antibiotic and continuous veino-veinous hemodialysis
Secondary	Distribution of steady state beta-lactam concentrations and their variability	Description of beta-lactam concentration	Day 3 after start of antibiotic and continuous veino-veinous hemodialysis
Secondary	Incidence of neurotoxicity	Percentage of neurotoxicity	Day 7 after start of antibiotic and continuous veino-veinous hemodialysis
Secondary	Trends in beta-lactam concentrations between 2 days	Comparaison between 24 hours and 48 hours samples	At Day 1 and Day 2
Secondary	Clinical response observed when beta-lactam concentrations achieved 5 MIC	Survival at Day 28 and Day 90	At Day 28 and day 90

External Links

•   SFAR, SFPT, Recommandations de Pratiques Professionnelles, Optimisation du traitement par bêta-lactamines chez le patient de soins critiques 2018.