Vancomycin and Cefoxitin During Pediatric Cardiopulmonary Bypass (VANCOCEF)

Vancomycin and Cefoxitin Levels During Pediatric Cardiac Surgery With Cardiopulmonary Bypass

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.

Study Overview

• Status: Completed
• Conditions: Congenital Heart Disease
• Intervention / Treatment: Other: vancomycin pharmacokinetics; Other: cefoxitin pharmacokinetics

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 Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy, 00165
    • Terapia Intenisva Cardiochirurgica

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children undergoing cardiac surgery requiring cardiopulmonary bypass and antibiotic prophylaxis with vancomycin and cefoxitin

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
vancomycin and cefoxitin pharmacokinetics; This is surgical prophylaxis and cefoxitin/vancomycin have to be administered to each patient of the study, before surgery	Other: vancomycin pharmacokinetics; vancomycin serial plasmatic and ultrafiltrate samples in order to assess plasmatic and ultrafiltrate drug concentrations; Other: cefoxitin pharmacokinetics; cefoxitin serial plasmatic and ultrafiltrate samples in order to assess plasmatic and ultrafiltrate drug concentrations

What is the study measuring?

Primary Outcome Measures

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	samples will be withdrawn: at skin incision, 15 minutes after CPB start (CPB1), at the end of CPB (CPB2), at end of surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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)	Ultrafiltrate sample will be withdrawn at the end of CPB (UF1)

Collaborators and Investigators

• Sponsor: Bambino Gesù Hospital and Research Institute

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2017
• Primary Completion (ACTUAL): December 20, 2017
• Study Completion (ACTUAL): July 1, 2019

Study Registration Dates

• First Submitted: July 10, 2016
• First Submitted That Met QC Criteria: July 20, 2016
• First Posted (ESTIMATE): July 21, 2016

Study Record Updates

• Last Update Posted (ACTUAL): January 14, 2020
• Last Update Submitted That Met QC Criteria: January 13, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: pharmacokinetics; cardiopulmonary bypass; antibiotic prophylaxis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Heart Defects, Congenital; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Cefoxitin
• Other Study ID Numbers: vanco and cefoxitin during CPB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO