Efficacy of Betalactam Antibiotics in Prolonged Infusion Compared to Intermittent in Pediatric Patients With Sepsis

Sepsis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03019965
• Other study ID #: 2016-785-099
• Status: Completed
• Phase: N/A
• Start date: February 1, 2017
• Est. completion date: January 30, 2020

Study information

• Verified date: July 2021
• Source: Coordinación de Investigación en Salud, Mexico
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 426
• Est. completion date: January 30, 2020
• Est. primary completion date: December 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Sepsis
• Toxemia

Intervention

Drug:
• Intermittent Piperacillin/tazobactam
Piperacillin/tazobactam administered in 30 minutes infusion.
• Continuous Piperacillin/tazobactam
Piperacillin/tazobactam administered in 24 hours infusion.
• Intermittent Imipenem
Imipenem administered in 60 minutes infusion.
• Extended Imipenem
Imipenem administered in 6 hours infusion.
• Intermittent Meropenem
Meropenem administered in 60 minutes infusion.
• Extended Meropenem
Meropenem administered in 8 hours infusion.

Locations

Country	Name	City	State
Mexico	Hospital Infantil de México Federico Gómez	Mexico	Distrito Federal
Mexico	Instituto Mexicano del Seguro Social	Mexico	Distrito Federal

Sponsors (4)

Lead Sponsor	Collaborator
Coordinación de Investigación en Salud, Mexico	Hospital Infantil de Mexico Federico Gomez, Hospital Regional de Alta Especialidad del Bajio, Instituto Mexicano del Seguro Social

Country where clinical trial is conducted

Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Clinical Response	Resolution. Disappearance of all signs and symptoms related to the infection.; Failure. Insufficient lessening of the signs and symptoms of infection to qualify as improvement, including death or indeterminate (no evaluation possible, for any reason).	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	Number of Participants With Adverse Events	Any harmful, undesirable, potentially serious and life threatening effects occurring during or after administration of the antibiotics proposed in this study (piperacillin / tazobactam, imipenem or meropenem), was evaluated as: none or adverse event classified according to the intensity of the clinical manifestation (severity) as: mild, moderate or severe and for each antibiotic.	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.