Vancomycin and Cefoxitin During Pediatric Cardiopulmonary Bypass

Completed

• Conditions: Congenital Heart Disease
• Interventions: Other: vancomycin pharmacokinetics; Other: cefoxitin pharmacokinetics

• Registration Number: NCT02839486
• Lead Sponsor: Bambino Gesù Hospital and Research Institute

Brief Summary

The aim of this study will be to evaluate vancomycin and cefoxitin blood levels during elective cardiopulmonary bypass (CPB) surgery in four pre-determined pediatric strata: neonates, infants, children weighting less than 40 kg and children weighting more than 40 kg.

Detailed Description

Few data are available in current literature about pharmacokinetics (PK) of antibiotics administered as surgical prophylaxis to children scheduled for cardiac surgery with CPB. In particular, vancomycin PK during CPB has been studied only in small case series, whereas no specific study has been conducted, so far, in the specific setting of children receiving cefoxitin during CPB.

CPB affects patients' volemia and drugs PK is eventually altered. On the other side during and after surgery for heart defects, many risk factors may decrease renal and hepatic clearance, including altered renal perfusion, use of vasoactive agents, and use of concomitant nephrotoxic medications.

Primary Objective of the study will be:

• To study the pharmacokinetic profile of vancomycin and cefoxitin administered, as antibiotic prophylaxis to children undergoing elective CPB.

Secondary Objectives will be:

* To evaluate if a significant difference in blood levels will occur in the four predetermined patients' categories.

* To evaluate the role of hemodilution during CPB on studied antibiotics' serum concentration

* To verify the incidence of post-operative infections in the studied population with particular attention to sensitive bacteria

* To evaluate the impact of ultrafiltration in studied antibiotics' clearance

* To evaluate safety of the administered antibiotics This is a prospective monocentric, open label, not controlled clinical trial.

Study Timeline

• Study First Submitted: 2016-07-10
• Study First Submitted QC: 2016-07-20
• Study First Posted: 2016-07-21
• Study Start: 2017-10-01
• Primary Completion: 2017-12-20
• Study Completion: 2019-07-01
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-13
• Last Update Posted: 2020-01-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Elective cardiac surgery schedule with the planned application of CPB
2. Parents of neonates, or their legal representative, able to consent and comply with protocol requirements.

Exclusion Criteria

1. Urgent or emergent surgery
2. Antibiotic therapy (any) administered before surgery
3. Patients receiving, before surgery, any other ofr of extracorporeal treatment (i.e extracorporeal membrane oxygenation, continuous renal replacement therapy)
4. Previous renal or hepatic dysfunction requiring need for antibiotic posology modification.
5. Surgery requiring antibiotic prophylaxis with different drug combinations (i.e vancomycin and gentamycin)
6. extremely low birth weight neonates.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
vancomycin and cefoxitin pharmacokinetics	cefoxitin pharmacokinetics	This is surgical prophylaxis and cefoxitin/vancomycin have to be administered to each patient of the study, before surgery
vancomycin and cefoxitin pharmacokinetics	vancomycin pharmacokinetics	This is surgical prophylaxis and cefoxitin/vancomycin have to be administered to each patient of the study, before surgery

Primary Outcome Measures

Name	Time	Method
vancomycin and cefoxitin concentration change in serial plasmatic samples	samples will be withdrawn: at skin incision, 15 minutes after CPB start (CPB1), at the end of CPB (CPB2), at end of surgery.	a 4-points pharmacokinetic curve per each antibiotic will be generated by serial average plasmatic vancomycin and cefoxitin concentration assessments.

Secondary Outcome Measures

Name	Time	Method
differences between pre-determined subgroups (neonates, infants, children weighting less than 40 kg and children weighting more than 40 kg) in plasmatic vancomycin and cefoxitin levels change at each time point	samples will be withdrawn: at skin incision, 15 minutes after CPB start (CPB1), at the end of CPB (CPB2).
vancomycin and cefoxitin clearance by ultrafiltration	Ultrafiltrate sample will be withdrawn at the end of CPB (UF1)	The clearance of vancomycin and cefoxitin in the ultrafiltrate (UF) will be evaluated. Antibiotics' sieving coefficient (SC) will be calculated from antibiotics concentrations at the following time points: UF1/\[(CPB1+CPB2)/2\]. Antibiotics clearance will be calculated as SC\*UF rate (ml/min)

Trial Locations

Locations (1)

Terapia Intenisva Cardiochirurgica; 🇮🇹 Roma, Italy