Clinical trial NCT03019965: Efficacy of Betalactam Antibiotics in Prolonged Infusion Compared to Intermittent in Pediatric Patients With Sepsis
Official title: Efficacy and Safety of the Administration of Betalactam Antibiotics in Continuous or Extended Infusion Compared to Intermittent Infusion in Patients With Sepsis in Two Pediatric Third-level Care Hospitals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sepsis
Lead sponsor: Coordinación de Investigación en Salud, Mexico
Sponsor class: OTHER_GOV
Collaborators: name: Instituto Mexicano del Seguro Social
name: Hospital Infantil de Mexico Federico Gomez
name: Hospital Regional de Alta Especialidad del Bajio
First posted: 2017-01-13
Enrollment: 426
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates the efficacy and safety of the administration of betalactam antibiotics in prolonged infusion compared to intermittent infusion in children with sepsis. Half of participants will receive piperacillin/tazobactam, imipenem or meropenem in continuous or extended infusion, while the other half will receive piperacillin/tazobactam, imipenem or meropenem in intermittent infusion.

Detailed description: Sepsis is the leading cause of morbidity and mortality in hospitalised patients globally. Betalactams are time-dependent antibiotics, and so, the duration of time for which the free drug plasma concentration remains above the minimum inhibitory concentration (fT \> MIC) is the pharmacokinetic/pharmacodynamic index associated with bacterial killing and clinical improvement. Numerous studies have demonstrated that continuous infusion (infusion in 24 hours) and extended infusion (through prolonging the infusion time to greater than 3 hours) allows the maintenance of concentrations above the MIC for a longer period of time within the dosing interval (30 minute or 1 hour), and so, capitalises on the pharmacodynamic properties of betalactams and maximises bacterial killing, therefore potentially improving clinical outcomes. In adult patients, the several studies suggest that prolonged infusion may offer clinical benefits and significant reduction in mortality without increasing the risk of toxicity, however, there is limited information about these dosing strategies in pediatric patients.

Eligibility criteria: Inclusion Criteria:

* Patients diagnosed with sepsis, who have been evaluated by an infectious physician and are candidates to receive piperacillin/tazobactam, imipenem or meropenem as empiric treatment.

Exclusion Criteria:

* Patients with a history of allergy to one or more of the proposed antibiotics.
* Patients with chronic kidney disease or acute renal failure.
* Patients with acute liver failure of any cause.
* Patients in palliative or supportive care only.

Primary outcomes:
measure: Number of Participants With Clinical Response
timeFrame: Number of participants with clinical response at 14 days after antibiotic cessation, up to an average of 28 days or the day of your discharge if this occurred before 14 days after antibiotic cessation.
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Number of participants with adverse events evaluated by an physician at the time of administration of antibiotics, up to an average to 24 hours after the study drug cessation.
Other outcomes:
Locations:
city: Mexico
country: Mexico
facility: Hospital Infantil de México Federico Gómez
state: Distrito Federal
city: Mexico
country: Mexico
facility: Instituto Mexicano del Seguro Social
state: Distrito Federal
Study officials:
affiliation: Instituto Mexicano del Seguro Social
name: Yazmín del Carmen Fuentes
role: PRINCIPAL_INVESTIGATOR
References: